Research Article

Comparative Study: Managing Hepatic and Renal Disorders Associated with Fatty Liver Using Natural and Conventional Preparations in Dogs

Mohamed Awny Ahmed Elkhiat1, Sabry Ahmed Mousa2, Mahmoud Saber Abdulkader1, Amr A. El-Sayed1, Mostafa El-Gaffary3, Mohamed Ibrahim Oraby1*

1Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt; 2Department of Veterinary Clinical Medical Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan; 3Department of Veterinary Clinical Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Received | April 28, 2025; Accepted | July 06, 2025; Published | July 23, 2025

*Correspondence | Mohamed Ibrahim Oraby, Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt; Email: [email protected]

Citation | Elkhiat MAA, Mousa SA, Abdulkader MS, El-Sayed AA, El-Gaffary M, Oraby MI (2025). Comparative study: Managing hepatic and renal disorders associated with fatty liver using natural and conventional preparations in dogs. Adv. Anim. Vet. Sci. 13(8): 1764-1772.

DOI | https://dx.doi.org/10.17582/journal.aavs/2025/13.8.1764.1772

ISSN (Online) | 2307-8316; ISSN (Print) | 2309-3331

Copyright: 2025 by the authors. Licensee ResearchersLinks Ltd, England, UK.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

INTRODUCTION

The liver is a vital organ in the body, being responsible for more than 500 different physiological functions, including fat digestion, metabolism, detoxification, immunity, blood clotting, and protein synthesis (Kalra and Tuma, 2018). Alongside the kidneys, it serves as a primary blood filter responsible for eliminating circulating toxins and waste products. The liver is susceptible to infectious and non-infectious diseases. Hepatic abnormalities resulting from various liver diseases can be easily diagnosed through liver function tests and by monitoring various hematological and blood biochemical parameters. These changes may involve the elevation of serum levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as disruptions in blood protein and lipid profiles. Sonography is an additional tool for diagnosing other hepatic disorders such as fatty liver, hepatomegaly, or neoplasms (Nausikaa et al., 2022; Tinted et al., 2023). Unlike farm animals, pets are regarded as family members and are cared for in households until their natural death. Therefore, older pets are susceptible to diseases associated with senility including liver, kidney, and heart diseases. They are also susceptible to several long-standing inflammatory diseases such as Canine Atopic Dermatitis and Idiopathic inflammatory bowel disease which usually treated by steroidal and non-steroidal anti-inflammatory drugs (Santoro, 2019; Khan and McLean, 2012; Jergens et al., 1992). However, the use of several anti-inflammatory drugs in pets could result in serious adverse effects specially on the nervous system, liver and kidneys. The animals usually develop hepatic and renal disorders and gastro-intestinal disturbances in the form of vomiting and diarrhoea (Jones et al., 1992; McLean and Khan, 2018; Lascelles et al., 2007; Villar et al., 1998; Khan and McLean, 2012; Stokes and Forrester, 2004; Cortinovis et al., 2015; Herrero et al., 2022; Chalifoux et al., 2023).

The pathological changes in the liver starts to occur within 2 – 3 days after the beginning of the therapy with corticosteroids (Dillon et al., 1980; Center et al., 2005). Even a single standard dosage can induce statistically significant increase in the values of alkaline phosphatase (ALP) after 24 hours from the injection time and the values of both (ALT) and (ALP) in dogs’ blood serum after 48 hours from the injection time (Kondratjeva and Birgele, 2014a). Cases of steroid hepatopathy are well documented in dogs subjected to long term or high doses treatment with steroidal anti- inflammatory which is attributed to corticosteroid induced alterations in the liver morpho-functional condition (Fittschen and Bellamy, 1984; Feldman and Nelson, 2004). This condition is not only limited to hepatocyte injury but can also lead to liver fibrosis due to the specific reaction of liver stellate Ito cells as well (Sobczak-Filipiak et al., 2014).

To our knowledge, Herb-All™ LIVER is widely used in farm animals but not in the pet sector. The preparation is used to control fatty liver in layers and in transient dairy cows also to protect and revitalize the liver tissues from the harming effects of mycotoxin and insecticides/ chemical residues in their feed (Fayed et al., 2023; Liaqat et al., 2023). It can even be supplemented to support the liver against infectious agents targeting the liver like Inclusion Body Hepatitis in poultry and Hepatopancreatitis in shrimps as declared by the manufacturer. On the other hand, hepatic disorders in pet sector are commonly treated with conventional therapeutics such as Ornipural® injections. The product is commonly used for the treatment of liver problems of both infectious and non-infectious causes (Anugrah et al., 2023). In the present work, the effect of supplementation of dog feed with the natural product Herb-All™ LIVER was studied in dogs suffering from different hepatic disorders. The efficiency of this approach was compared with the results achieved via the application of conventional approach using Ornipural® injections in the control group.

MATERIAL AND METHODS

Ethical Statements

This study was approved by the Veterinary Medicine Cairo University Institutional Animal Care and Use Committee (Vet CU13102024949) and adhered to ARRIVE guidelines for animal research.

Investigated Dogs

In the present work, dogs housed in a pet animal shelter were chosen for the investigation. The shelter caters to old, diseased and homeless pets. Among the 94 dogs kept in the shelter, several dogs had hepatic and renal disorders with a previous history of viral infections, exposure to chemicals (mainly insecticides) / high doses of medications (mainly anti-inflammatories), or fatty liver in sequence of long-term treatment with corticosteroids due to chronic inflammatory diseases. A total of 23 mixed breed stray dogs exhibiting the most severe clinical signs were selected and delivered to the clinic of Internal Medicine, Faculty of Veterinary Medicine, Cairo University for treatment of hepatic and renal disorders. Out of these, 11 dogs had a history of previous medication with steroidal anti-inflammatory preparations. The dogs suffered from hepatopathy associated with signs of fatty liver and renal disorders called D [diseased control]. The dogs were randomly divided into group 1 (G1) consisted of six dogs which were supplemented with Herb-All™ LIVER in their feed, while the second group (G2) consisted of five dogs (treated with Ornipural® injections). The treatment duration was 30 days, during which all dogs fed the same commercial dry feed. The feed was supplemented with Herb-All™ LIVER only for G1. Prior to the trial begin the dogs underwent a preparatory phase for two weeks involved deworming, and vaccination against rabies. The data obtained from both G1 and G2 groups were compared with the primary values of the diseased dogs before treatment (D group).

Clinical Pictures

The dogs were presented with complaints of emaciation, poor health condition, and icterus. Their medication history indicated their previous treatment for dermatological inflammatory diseases with steroidal anti-inflammatory. The expressed clinical picture included vomiting, diarrhoea, weakness, skin lesions especially on the abdominal aspect, partial alopecia and severe emaciation. Ultrasonic examination revealed the presence of fatty liver. Laboratory examinations referred to an increase in the liver and kidney function parameters.

Medications

G1 was supplemented with Herb-All™ LIVER in their feed (Life Circle Nutrition, Switzerland, 2.5 gm/ dog/day). Herb-All™ LIVER consists of several herbs including Tinospora cordifolia and Androgrphis paniculata. No data could be obtained about the other herbs involved in the formulation.

G2 was treated with Ornipural® injections, Vetoquinol, France (5ml / dog/ day given I/M). Ornipural® is routinely administered to treat hepatic and kidney disorders in pet animals. Composition: Arginine (hydrochloride), Ornithine (hydrochloride), Citrulline, Sorbitol, and Metacresol.

Laboratory Examinations and Ultrasonography

The laboratory examinations were conducted by ProCyte Hematology Analyzer, IDEXX Reference Laboratories, USA. Every time before blood sampling the dogs were fasted for 18 hours. The ultrasonic examination was carried out using Esaote Veterinary MyLabOne, mod. 8100, and using micro convex probe, from Esaote Europe B.V., Netherland.

The liver function test included: Glutamate pyruvate transaminase (GPT), also known as alanine aminotransferase (ALT) and glutamate oxaloacetate transaminase (GOT), also known as aspartate aminotransferase (AST) and the Total bilirubin (T Bil). The Kidney function test was represented by Blood urea nitrogen (BUN) and Creatinine (Cr). The blood biochemistry involved the blood lipid parameters (Triglycerides (TG), total cholesterol (TC), very low-density lipoprotein (VLDL) cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol. Meanwhile, the monitored hematological parameters were the red blood cells (RBCs), Hemoglobin (HB), Platelets, Hematocrit, mean corpuscular hemoglobin concentration (MCHC), the mean hemoglobin content (MCH), in addition to the total white blood cell counts (WBCs) and the differential count for the different WBCs types including the Basophil, Eosinophil, Staff, Segmented, Lymphocytes and Monocytes.

Statistical Analysis

To test the effect of both treatments on each studied hematological and serum parameter, a one-way analysis of variance (ANOVA) was used to evaluate the difference between the diseased group (D) and the two treatment groups (G1 and G2). Paired sample T-test was used to test the difference between each diseased and treatment group. The Shapiro–Wilk test was utilized for normality analysis of the variables and Levene’s test was used to evaluate the homogeneity of variance. Parametric statistical tests were used for analyzing data with a normal distribution, and if there were significant differences, the Least significant difference (LSD) test was used for post‐hoc analysis. The non‐parametric tests were used for data that were not normally distributed. Data was presented as the mean ± standard error (SE). Statistical significance was set at P < 0.05. All analyses were performed with SPSS® version 20.

RESULTS

The statistical analysis of hematological and biochemical variables obtained data is presented in Tables 1 and 2. The white blood cells (WBCs) showed a significant decrease in G1 (Herb-All™ LIVER supplemented) and G2 (injected with Ornipural®) when compared to the primary values of the diseased dogs (D group). Eosinophils significantly increased in G1 than D group while G2 showed non-significant difference if compared to G1 and D group. Segmented neutrophils decreased significantly in G1 compared to G2 which showed significant decrease in neutrophils compared to D group. Lymphocytes increased significantly in G1 and G2 groups than D group. MCH decreased significantly in G1 and G2 groups than D group. MCHC in G2 was significantly lower than its starting value, while in G1 its value showed a nonsignificant decrease and increase if compared to D and G2 groups, respectively. Other hematological variables revealed non-significant differences between groups. Statistical analysis of obtained results of serum biochemical variables is shown in Table 2. GPT, GOT, HDL and total bilirubin in G1 and G2 groups were significantly lower than their values in D group. BUN in G1 showed significant and non-significant decrease if compared to D and G2 groups, respectively. Creatinine and cholesterol in G1 and G2 increased significantly compared to D group. Triglycerides in G2 were significantly lower than their value in G1 which revealed a significant decrease compared to D group. VLDL in G2 showed significant increase if compared to D group but a non-significant increase compared to G1. LDL revealed non-significant differences within groups. The data obtained from the laboratory investigations were confirmed by the data delivered by ultrasonic examination as shown in Figures 1 and 2.

DISCUSSION

The resulting damage of the liver tissues of dogs due to steroid hepatopathy is indicated by the significant increase in the levels of many serum enzymes such as alanine amino transferase (ALT), aspartate amino transferase (AST), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP) and corticosteroid-induced thermostable alkaline phosphatase (cAP) (Badylak and van Vleet, 1981; Lucena et al., 1999).

 

In the present work, herbal based hepato-protectant (Herb-All™ LIVER, G1 group) was compared with a traditional one (Ornipural®, G2 group) for treatment of hepatic and renal disorders associated with fatty liver and steroidal anti-inflammatory induced hepatopathy in 11 dogs. Although both Ornipural® and Herb-All™ LIVER possesses well documented hepato-renal protective potential in the veterinary field, the use of Herb-All™ LIVER is usually limited to farm animals (El Okle et al., 2022; Fayed et al., 2023). In contrast to the results achieved from the present work, previous attempts to treat dogs suffering from hepatopathy using herbal hepato-protectant containing silymarin, curcuma and artichoke for 30 days could only achieve partial success in the reduction of elevated enzymes, yet the reduction was not enough to fall again in the normal/ physiological reference ranges (Kondratjeva and Birgele, 2014a, b).

 

However, supplementation with Andrographis paniculata extract could correct the damage, as evidenced by laboratory, histopathological investigations, and ultrasonic examinations (Pattanaik et al., 2013). The difference in results between the herbs is attributed to the superior hepato-protective capacity of Andrographis paniculata when compared to that of silymarin (Jayakumar et al., 2013). Considering serum biochemical parameters studied in the present work, tested liver enzymes and total bilirubin returned to reference range in both treatment group, however, GPT was lower after herbal treatment than traditional one (Table 2) and this may be achieved due to the potent anti-inflammatory effect of Andrographis paniculata (Jarukamjorn and Nemoto, 2008) and Tinospora cordifolia present in Herb-All™ LIVER (Shukla et al., 1992; Trivedi and Rawal, 2001; Kumar et al., 2013; Kavitha et al., 2011; Singh et al., 2015).

 

Table 1: Hematological parameters in diseased control group of dogs before treatment (D group) in comparison to both treatment groups after one month (Herb-All™ LIVER group (G1) and Ornipural® group (G2)). The different letters (a, b, c) are used to refer to significance, when the letters in one raw differ, it means significant difference at P < 0.05.

Variables	Average starting value before treatment (D group)	Average Herb-All™ LIVER group after one month (G1)	Average Ornipural® group after one month (G2)	Reference range
RBCs	5.82 ± 0.25a	6.31 ± 0.17a	5.92 ± 0.24a	5.5-8.5 ×10⁶/mm³
Hemoglobin	13.52 ± 0.51a	13.35 ± 0.36a	12.44 ± 0.58a	12-18 gm
Platelets	222727.27 ± 23298.31a	301833.33 ± 30852.17a	273600.00 ± 54227.37a	200-500 /mm3
Hematocrit	41.18 ± 1.27a	42.83 ± 0.72a	41.00 ± 0.89a	39% - 55 %
WBCs	20890.91 ± 1746.28a	10350.00 ± 695.12b	10240.00 ± 1138.63b	6-15 ×103/mm³
Basophil	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0 – 1 %
Eosinophil	2.36 ± 0.23b	4.83 ± 1.07a	3.20 ± 0.44ab	2-10 %
Staff	2.00 ± 0.00a	2.33 ± 0.30a	2.00 ± 0.00a
Segmented	65.45 ± 2.61a	28.00 ± 3.68c	44.00 ± 2.77b	40-80 %
Lymphocytes	8.55 ± 0.78b	36.83 ± 7.64a	29.20 ± 2.86a	10 – 36 %
Monocytes	21.64 ± 2.42a	28.00 ± 3.97a	21.60 ± 1.31a	0– 13%
MCV	71.10 ± 0.96a	68.02 ± 1.06a	69.52 ± 1.68a	60-77 fl
MCH	23.21 ± 0.25a	21.13 ± 0.39b	20.96 ± 0.43b	19.1-26.2 pg
MCHC	32.72 ± 0.41a	31.10 ± 0.58ab	30.24 ± 0.86b	32 - 36 g %

 

RBCs: Red Blood Cells; WBCs: White Blood Cells; MCV: Mean Corpuscular Volume; MCH: Mean Corpuscular Hemoglobin; MCHC: Mean Corpuscular Hemoglobin concentration.

 

Table 2: Serum biochemical parameters in diseased control group of dogs before treatment (D group) in comparison to both treatment groups after one month (Herb-All™ LIVER group (G1) and Ornipural® group (G2)). The different letters (a, b, c) are used to refer to significance, when the letters in one raw differ, it means significant difference at P < 0.05.

Variables	Average starting value before treatment (D group)	Average Herb-All™ LIVER group after one month (G1)	Average Ornipural® group after one month (G2)	Reference range
ALT (GPT)	284.27 ± 34.79a	31.33 ± 2.77b	42.60 ± 6.92b	(10 - 109 IU/L)
AST (GOT)	150.73 ± 26.99a	22.17 ± 0.98b	20.60 ± 1.12b	(16 - 54 IU/L)
T. Bilirubin	1.83 ± 0.26a	0.14 ± 0.02b	0.12 ± 0.01b	(0-0.3 mg/dL)
BUN	10.64 ± 0.53a	8.83 ± 0.28b	10.00 ± 0.28ab	(8 - 28 mg/dL)
Creatinine	0.54 ± 0.02b	0.93 ± 0.04a	0.96 ± 0.03a	(0.7 - 1.5 mg/dL)
Cholesterol	141.45 ± 11.49b	317.67 ± 24.97a	294.40 ± 21.66a	(133–367 mg/dL)
Triglycerides	55.82 ± 5.32c	90.00 ± 2.53b	123.00 ± 18.50a	(30–141 mg/dL)
HDL (mg/dL)	37.82 ± 3.14a	21.50 ± 0.66b	24.00 ± 1.44b	Not Normalized
VLDL (mg/dL)	13.82 ± 1.97b	23.00 ± 0.47ab	31.40 ± 6.24a	Not Normalized
LDL (mg/dL)	21.73 ± 1.40a	21.00 ± 1.70a	18.40 ± 1.31a	Not Normalized

 

ALT: Alanine Aminotransferase; GPT: Glutamate Pyruvate Transaminase; AST: Aspartate Aminotransferase; GOT: Glutamate Oxaloacetate Transaminase; T. Bilirubin: Total Bilirubin; BUN: Blood Urea Nitrogen; HDL: High-Density Lipoprotein; VLDL: Very Low-Density Lipoprotein; LDL: Low-Density Lipoprotein.

 

Although the corticosteroids can directly affect the dog`s kidney performance through influencing the tubular electrolyte handling and absorptive capacities and indirectly through their effect on blood pressure, renal blood flow and glomerular function, the seen damages in the investigated dogs as evidence by the pathological changes in laboratory tests and ultrasonic investigation are most probably induced by chronic exposure to chemicals or infectious agents rather than being induced by the given steroidal anti-inflammatory drugs (Smets et al., 2010).

The reported improvement of kidney performance upon supplementation with the herbal mixture is attributed to the protective effect of both declared herbs in Herb-All™ LIVER against nephropathy and chemical-induced renal failure (Hidayat and Wulandari, 2021; Singh et al., 2009; Adeoye et al., 2018; Gupta and Sharma, 2011). This explains the reduction in blood urea nitrogen (BUN) in response to Herb-All™ LIVER treatment. Urea nitrogen concentrations were significantly lower than its value before treatment and non-significantly lower than its value after traditional treatment in agreement with the results delivered by Fayed et al. (2023). The use of both parameters BUN and creatinine in combination to detect the kidney performance was recommended by several authors due to the limited sensibility and specificity of BUN as a marker when applied alone for this purpose (De Santis et al., 2022).

Despite the non-significant differences in the variables of erythrogram between G1 and G2, these values revealed higher levels after Herb-All™ LIVER supplementation than the values reported following treatment with the conventional therapy which could be attributed to the hematinic property of herbs involved in Herb-All™ LIVER or due to revitalization of liver cells, leading to a general improvement in the health condition of the dogs.

Regarding leukogram, total white blood cells and lymphocytes returned to the reference range in both treated groups, however eosinophil count showed significant increase after Herb-All™ LIVER treatment. On the other hand, the count of segmented neutrophils after traditional treatment was significantly lower than before starting the treatment (D group; Table 1) which could be attributed to relief of suspected secondary bacterial infection induced by immunosuppressive effect of corticosteroid, in addition to segmented neutrophils after herbal treatment (G1) was significantly lower than its value after traditional treatment (G2) and this could be referred to immunomodulatory activity of Herb-All™ LIVER (Fayed et al., 2023; Yadav et al., 2016; Rajanna et al., 2021). Another explanation for the reduction in neutrophil count is the post therapeutic effect of steroidal anti-inflammatory preparations. It is well documented that the number of segmented WBCs (neutrophils) usually decrease after stoppage of cortisone treatment, as cortisone leads to stop in neutrophil apoptosis and therefore increase their number (Liles et al., 1995). The high concentrations of antioxidants present in Herb-All™ LIVER and its hepatocytes revitalization capacity according to the manufacturer might be the cause of the improvement of the general health condition which is, in turn, reflected on the improvement of hematological and biochemical parameters (Sharma and Joshi, 2011; Hussien et al., 2023). Although cholesterol and creatinine levels increased in both treatment groups, their values were still within the reference range. However, the VLDL value was significantly increased only in Ornipural® group, in contrast to Herb-All™ LIVER supplemented group which did not reveal significant difference. Triglycerides was significantly lower after Herb-All™ LIVER supplementation than its value after injecting the dogs with Ornipural® which can be attributed to the hypolipidemic property of Andrographis paniculata and Tinospora cordifolia which favored their use for the treatment of insulin resistance, diabetes melitus and fatty liver in Ayurvedic medicine (Sinha et al., 2004; Shirolkar et al., 2020; Sivakumar and Rajan, 2011; Sharma et al., 2015; Jaiyesimi et al., 2020; Kumar et al., 2021). Finally, the enhancement in the overall body condition of the dogs was linked to the correction of the disturbed physiological parameters and the revitalization of liver tissues. This led to improved metabolic efficiency and increased appetite, attributable to the increase of bile production due to the choleretic effect of Herb-All™ LIVER (Shukla et al., 1992).

The ultrasonographic assessment done in this study gave crucial real-time imaging of both renal and hepatic structural changes in dogs with corticosteroid-induced renal insufficiency and hepatopathy. The dogs, before treatment commenced, had classic sonographic findings of fatty liver disease that comprised heightened hepatic echogenicity, liver enlargement, poorly defined portal vein borders, and anisotropic variation among hepatic lobes. The results produced match the ultrasonographic characteristics of hepatic lipidosis and vacuolar hepatopathy found in previous studies (Nyland and Mattoon, 2014; Murayama et al., 2020).

Following one month of treatment, there was significant improvement in hepatic echotexture in both Ornipural® and Herb-All™ LIVER groups. Treated dogs (Canis lupus familiaris) particularly showed reduced echogenicity, normalization of liver size, and enhanced visibility of portal vein walls, indicative of hepatic steatosis and fibrosis regression.

The decrease in echogenicity, from hyperechoic to isoechoic or mildly hypoechoic compared to the spleen and falciform fat, was strongly associated with the marked reductions in serum ALT, AST, and total bilirubin levels, indicating enhanced hepatocellular integrity and biliary function (Kondratjeva and Birgele, 2014; Kim et al., 2019). Within the Herb-All™ LIVER -treated group, there were notable changes in echogenicity with the liver parenchyma transforming to heterogeneous but hypoechoic texture, a sign of hepatocellular regeneration and augmented perfusion. These enhancements were supported by the normalization of lipid profiles - most notably characterized by reduced triglycerides and elevated HDL - thereby enhancing the resolution of hepatic steatosis (Sahin et al., 2018; Zhang et al., 2020).

Sonographic findings will reveal a decrease in intracellular lipid content alongside an increase in hepatic blood flow, thereby enhancing the liver’s detoxification processes and its ability to synthesize proteins.

Renal ultrasonography also showed mild enhancements. In a few, before treatment commenced, the renal cortices had a mildly hyperechoic pattern, which has been due to chronic renal stress or incipient nephropathy (Baral et al., 2020). Post-treatment ultrasound revealed improvement in cortical echotexture and a restoration of cortico-medullary differentiation, which correlated with the said reductions in blood urea nitrogen (BUN) levels and stabilization of serum creatinine, especially in the Herb-All™ LIVER group. These improvements can be explained by the nephroprotective effects of Tinospora cordifolia and Andrographis paniculata, which have been previously reported to modulate renal oxidative stress and enhance glomerular function (Saha et al., 2016; Ahmad et al., 2018). Conclusively, the sonographic results not only corroborated the laboratory findings but also established a non-invasive means of dynamic evaluation of hepatic and renal recovery. Ultrasonography has thus demonstrated its indispensability in the monitoring of therapeutic responses, thereby solidifying its position as a fundamental diagnostic and follow-up technique in veterinary internal medicine (Lamb and Wisner, 2013; Murayama et al., 2020).

CONCLUSIONS AND RECOMMENDATIONS

This study offers compelling initial evidence for the herbal supplement Herb-All™ LIVER in the management of corticosteroid-induced fatty liver in canines. Both Herb-All™ LIVER and Ornipural® significantly decreased liver enzyme levels, serum bilirubin, and renal function, and showed significant clinical and ultrasound improvement. Herb-All™ LIVER offers obvious benefits in lipid profile management and cost and is a rational and cost-effective choice for long-term liver support in the veterinary clinic.

In view of the increasing concern regarding the side effects of long-term corticosteroid therapy in companion animals, the incorporation of natural hepatoprotective drugs such as Herb-All™ LIVER in therapeutic regimens can provide a more benign and sustainable alternative. However, additional research involving larger populations, exhaustive histopathological assessments, and clarification of the molecular modes of action is needed to comprehensively substantiate these results and facilitate evidence-based implementation of such phytogenic treatments in small animal practice.

ACKNOWLEDGEMENTS

We should thank the Department of Internal Medicine, Faculty of Veterinary Medicine, Cairo University, Egypt where the experimental trial was carried out.

NOVELTY STATEMENT

This is the first study to evaluate the efficacy of Herb-All™ LIVER, a herbal blend previously limited to livestock, in treating steroid-induced fatty liver and renal disorders in dogs. Our findings demonstrate its cost-effectiveness (92% lower daily cost vs. Ornipural®) and comparable therapeutic outcomes, offering a novel, sustainable alternative for veterinary practice.

AUTHOR’S CONTRIBUTIONS

Mohamed Awny Ahmed Elkhiat: Conceptualization, Data curation, Writing – original draft, Sabry Ahmed Mousa: Methodology, Formal analysis, Mahmoud Saber Abdulkader: Investigation, Visualization, Amr A. El-Sayed: Resources, Supervision, Mostafa El-Gaffary: Validation, Writing – review, editing and Mohamed Ibrahim Oraby: Project administration, Writing – review, editing and correspondence for submission.

Data Availability

All data generated during this study are presented in the manuscript.

Ethical Approval

This study was approved by the Veterinary Medicine Cairo University Institutional Animal Care and Use Committee (Vet CU13102024949) and adhered to ARRIVE guidelines for animal research.

Conflict of Interest

The authors declare no competing financial or personal interests that could influence this work.

REFERENCES

Adeoye BO, Asenuga ER, Oyagbemi AA, Omobowale TO, Adedapo AA (2018). The protective effect of the ethanol leaf extract of Andrographis paniculata on cisplatin-induced acute kidney injury in rats through nrf2/KIM-1 signaling pathway. Drug Res., 68(01): 23-32. https://doi.org/10.1055/s-0043-118179

Ahmad MK, Mahdi AA, Shukla KK, Islam N, Rajender S, Madhukar D (2018). Tinospora cordifolia as a potential immunomodulator and nephroprotective agent: Evidence from experimental studies. J. Ayurveda Integr. Med., 9(3): 222–228.

Anugrah D, Apada AMS, Rell F, Suharto RH, Mursalim MF (2023). Treatment of Leptospira infection in dog at Pet Vet. Clin. Central Jakarta. https://doi.org/10.20473/mkh.v34i3.2023.189-197

Badylak SF, Van Vleet JR (1981). Sequential morphologic and clinicopathologic alterations in dogs with experimentaly induced glucocorticoid hepatopathy. Am. J. Vet. Res., 42: 1310-1318. https://doi.org/10.2460/ajvr.1981.42.08.1310

Baral RM, Choudhary P, Banerjee A (2020). Sonographic diagnosis and grading of chronic kidney disease in dogs. J. Anim. Res., 10(6): 995–1000.

Center SA, Warner KL, McCabe J, Foureman P, Hoffmann WE, Erb HN (2005). Evaluation of the influence of S-adenosylmethionine on systemic and hepatic effects of prednisolone in dogs. Am. J. Vet. Res., 66: 330-341. https://doi.org/10.2460/ajvr.2005.66.330

Chalifoux NV, Butty EM, Mauro KD, Moyle RB, Ehrhardt CM, Robertson JB, Lynch AM (2023). Outcomes of 434 dogs with non‐steroidal anti‐inflammatory drug toxicosis treated with fluid therapy, lipid emulsion, or therapeutic plasma exchange. J. Vet. Intern. Med., 37(1): 161-172. https://doi.org/10.1111/jvim.16603

Cortinovis, Cristina, Fabiola Pizzo, Francesca Caloni (2015). Poisoning of dogs and cats by drugs intended for human use. Vet. J., 203(1): 52-58. https://doi.org/10.1016/j.tvjl.2014.11.004

De Santis F, Boari A, Dondi F, Crisi PE (2022). Drug-Dosing Adjustment in Dogs and Cats with Chronic Kidney Disease. Animals, (Basel). 12(3):262. https://doi.org/10.3390/ani12030262

Dillon AR, Spano JS, Powers RD (1980). Prednisolone induced haematological, biochemical and histological changes in the dog. J. Am. Anim. Hosp. Assoc., 16: 831-837.

El Okle OS, Tohamy HG, Althobaiti SA, Soliman MM, Ghamry HI, Farrag F, Shukry M (2022). Ornipural® Mitigates Malathion-Induced Hepato-Renal Damage in Rats via Amelioration of Oxidative Stress Biomarkers, Restoration of Antioxidant Activity, and Attenuation of Inflammatory Response. Antioxidants (Basel), 11(4):757. https://doi.org/10.3390/antiox11040757

Fayed RH, Rashad E, El-Samannoudy SI, Elsherif HMR, Ella HA, Ismael E (2023). Mitigative Effect of Dietary Tinospora cordifolia and Andrographis paniculata on Health and Hepato-renal Expression of Caspase-3 and TNF-α of Broiler Chickens Fed on Aflatoxin and Ochratoxin Contaminated Diet. J. Adv. Vet. Res., 13(8): 1668-1677

Feldman EC, Nelson RW (2004). Canine and Feline Endocrinology and Reproduction, Elsevier Science, Sounders, USA, 1104.

Fittschen C, Bellamy JE (1984). Prednisone-induced morphologic and chemical changes in liver of dogs. Vet. Pathol., 21: 399-406. https://doi.org/10.1177/030098588402100406

Gupta R, Sharma V (2011). Ameliorative effects of tinospora cordifolia root extract on histopathological and biochemical changes induced by aflatoxin-b(1) in mice kidney. Toxicol. Int., 18(2):94-8. https://doi.org/10.4103/0971-6580.84259

Herrero Y, Iannucci C, Schreiber N, Hansen BD, Vigani A (2022). Acute nephrotic-range glomerular proteinuria following ibuprofen intoxication in two cats. J. Feline Med. Surg. Open Rep., 8(1): 20551169221104551. https://doi.org/10.1177/20551169221104551

Hidayat R, Wulandari P (2021). Effects of Andrographis paniculata (Burm. F.) Extract on Diabetic Nephropathy in Rats. Rep. Biochem. Mol. Biol., 10(3):445-454. https://doi.org/10.52547/rbmb.10.3.445

Hussien HT, Tag HM, Ahmed E, Nabil ZI, El-Naggar MS (2023). The antioxidant and hepatoprotective activities of the ethanolic extract of tinospora cordifolia leaves: in vitro and in vivo studies. Egypt. J. Zool., 79(79): 48-65.

Jaiyesimi KF, Agunbiade OS, Ajiboye BO, Afolabi OB (2020). Polyphenolic-rich extracts of Andrographis paniculata mitigate hyperglycemia via attenuating β-cell dysfunction, pro-inflammatory cytokines and oxidative stress in alloxan-induced diabetic Wistar albino rat. J. Diabetes Metab. Disord., 19(2):1543-1556. https://doi.org/10.1007/s40200-020-00690-2

Jarukamjorn K, Nemoto N (2008). Pharmacological aspects of Andrographis paniculata on health and its major diterpenoid constituent andrographolide. J. Health Sci., 54(4):370–381. https://doi.org/10.1248/jhs.54.370

Jayakumar T, Hsieh CY, Lee JJ, Sheu JR (2013). Experimental and Clinical Pharmacology of Andrographis paniculata and Its Major Bioactive Phytoconstituent Andrographolide. Evid. Based Complement Altern. Med., (1): 846740. https://doi.org/10.1155/2013/846740

Jergens AE, Moore FM, Haynes JS, Miles KG (1992). Idiopathic inflammatory bowel disease in dogs and cats: 84 cases (1987‐1990). J. Am. Vet. Med. Assoc., 201:1603‐1608. https://doi.org/10.2460/javma.1992.201.10.1603

Jones RD, Baynes RE, Nimitz CT (1992). Nonsteroidal anti-inflammatory drug toxicosis in dogs and cats: 240 cases (1989-1990). J. Am. Vet. Med. Assoc., 201(3):475-7. https://doi.org/10.2460/javma.1992.201.03.475

Kalra A, Tuma F (2018). Physiology, Liver; StatPearls Publishing: Treasure Island, FL, USA.

Kavitha BT, Shruthi SD, Rai SP, Ramachandra YL (2011). Phytochemical analysis and hepatoprotective properties of Tinospora cordifolia against carbon tetrachloride-induced hepatic damage in rats. J. Basic Clin. Pharm., 2(3):139-42. PMID: 24826014; PMCID: PMC3979222.

Khan SA, McLean MK (2012). Toxicology of frequently encountered nonsteroidal anti-inflammatory drugs in dogs and cats. Vet. Clin. North Am. Small Anim. Pract., 42(2):289-306. https://doi.org/10.1016/j.cvsm.2012.01.003

Kim MG, Lim JH, Kim MK, Yoon HY (2019). Evaluation of ultrasonographic findings and liver enzyme activities in dogs with vacuolar hepatopathy. J. Vet. Med. Sci., 81(2): 288–294.

Kondratjeva J, Birgele E (2014a). Corticosteroid-induced hepatopathy in dogs. Lativia Univ. Agric., 21: 179-82.

Kondratjeva J, Birgele E (2014b). Corticosteroid-induced alteration in liver function in dogs and its decrease possibilities. Res. Rural Dev., 1 (1): 195-198..

Kondratjeva R, Birgele E (2014). Ultrasonographic evaluation of hepatic pathology in dogs with corticosteroid-induced liver changes. Vet. Radiol. Ultrasound, 55(5): 550–557.

Kumar S, Singh B, Bajpai V (2021). Andrographis paniculata (Burm. f.) Nees: Traditional uses, phytochemistry, pharmacological properties and quality control/quality assurance. J. Ethnopharmacol., 275: 114054. https://doi.org/10.1016/j.jep.2021.114054

Kumar, Vipin, Pankaj K, Modi, Saxena KK (2013). Exploration of hepatoprotective activity of aqueous extract of Tinospora cordifolia-an experimental study. Asian J. Pharm. Clin. Res., 6(1): 87-91.

Lamb CR, Wisner ER (2013). Diagnostic imaging of liver disease in small animals. Vet. Clin. North Am. Small Anim. Pract., 43(4): 751–765.

Lascelles BDX, Court MH, Hardie EM, Robertson SA (2007). Nonsteroidal anti-inflammatory drugs in cats: a review. Vet. Anaesth. Analg., 34(4): 228-250. https://doi.org/10.1111/j.1467-2995.2006.00322.x

Liaqat S, Yousaf M, Ahmad F, Saleemi MK (2023). Impact of poultry oil supplementation on liver health and fatty liver syndrome in caged layers. Pak. J. Agric. Sci., 60(3): 401-407. https://doi.org/10.21162/PAKJAS/23.111

Liles, W Conrad, David C Dale, Seymour J Klebanoff (1995). Glucocorticoids inhibit apoptosis of human neutrophils. Blood. 86: 3181-3188. https://doi.org/10.1182/blood.V86.8.3181.3181

Lucena R, Ginel PJ, Novales M, Molleda JM (1999). Effects of dexamethasone administration on serum trypsin-like immunoreactivity in healthy dogs. Am. J. Vet. Res., 60: 1357- 1359. https://doi.org/10.2460/ajvr.1999.60.11.1357

McLean MK, Khan SA (2018). Toxicology of frequently encountered nonsteroidal anti-inflammatory drugs in dogs and cats: an update. Vet. Clin. Small Anim. Pract., 48(6): 969-984. https://doi.org/10.1016/j.cvsm.2018.06.003

Murayama T, Koie H, Sato T, Sakai M (2020). Usefulness of ultrasound in the evaluation of corticosteroid-induced hepatopathy in dogs. Vet. Radiol. Ultrasound, 61(1): 77–84. https://doi.org/10.1111/vru.12815

Nausikaa Devriendt, Gonçalo Serrano, Emmelie Stock, Dominique Paepe, Hilde de Rooster (2022). Diagnostic value of liver function tests and ultrasonography in dogs with suspected congenital portosystemic shunts. Vet. Rec., 190(10): e 1381. https://doi.org/10.1002/vetr.1381

Nyland TG, Mattoon JS (2014). Small Animal Diagnostic Ultrasound (3rd ed.). Elsevier Saunders.

Pattanaik PK, Sahoo N, Parida GS (2013). Therapeutic efficacy of andrographis paniculata against hepatopathy in dogs. Indian J. Canine Pract., 5(1): 15.

Rajanna M, Bharathi B, Shivakumar BR, Deepak M, Prashanth D, Prabakaran D, Vijayabhaskar T, Arun B (2021). Immunomodulatory effects of Andrographis paniculata extract in healthy adults - An open-label study. J. Ayurveda Integr. Med., 12(3):529-534. https://doi.org/10.1016/j.jaim.2021.06.004

Saha S, Ghosh S, Mondal S (2016). Hepatoprotective activity of Tinospora cordifolia in various experimental models. J. Pharmacogn. Phytochem., 5(3): 162–165.

Sahin A, Erdogan G, Bilici M (2018). Effect of high-fat diet-induced fatty liver on biochemical and sonographic parameters in dogs. Turk. J. Vet. Anim. Sci., 42(2): 123–130.

Santoro D (2019). Therapies in Canine Atopic Dermatitis: An Update. Vet. Clin. North Am. Small Anim. Pract., 49(1):9-26. https://doi.org/10.1016/j.cvsm.2018.08.002

Sharma MEENU, Joshi SUMAN (2011). Comparison of anti-oxidant activity of Andrographis paniculata and Tinospora cordifolia leaves. J. Curr. Chem. Pharm. Sci., 1: 1-8.

Sharma R, Amin H, Prajapati PK (2015). Antidiabetic claims of Tinospora cordifolia (Willd.) Miers: critical appraisal and role in therapy. Asian Pac. J. Trop. Biomed., 5(1): 68-78. https://doi.org/10.1016/S2221-1691(15)30173-8

Shirolkar A, Yadav A, Mandal, TK, Dabur R (2020). Intervention of Ayurvedic drug Tinospora cordifolia attenuates the metabolic alterations in hypertriglyceridemia: a pilot clinical trial. J. Diabetes Metab. Disord., 19: 1367-1379. https://doi.org/10.1007/s40200-020-00657-3

Shukla B, Visen PK, Patnaik GK, Dhawan BN (1992). Choleretic effect of andrographolide in rats and guinea pigs. Planta Med., 58(2):146-149. https://doi.org/10.1055/s-2006-961416

Singh DP, Awasthi, H, Luqman S, Singh S, Mani D (2015). Hepatoprotective effect of a polyherbal extract containing Andrographis paniculata, Tinospora cordifolia and Solanum nigrum against paracetamol induced hepatotoxicity. Pharmacogn. Mag., 11(Suppl 3): S375. https://doi.org/10.4103/0973-1296.168945

Singh P, Srivastava MM, Khemani LD (2009). Renoprotective effects of Andrographis paniculata (Burm. f.) Nees in rats. Ups. J. Med. Sci., 114(3):136-9. https://doi.org/10.1080/03009730903174321

Sinha K, Mishra NP, Singh J, Khanuja SPS (2004). Tinospora cordifolia (Guduchi): a reservoir plant for therapeutic applications: A Review. Indian J. Trad. Knowledge, 3(3), 257-270

Sivakumar V, Rajan MD (2011). Hypoglycemic and antioxidant activity of Tinospora cordifolia in experimental diabetes. Int. J. Pharm. Sci. Res., 2(3): 608.

Smets P, Meyer E, Maddens B, Daminet S (2010). Cushing’s syndrome, glucocorticoids and the kidney. Gen. Comp. Endocrinol., 169(1): 1-10. https://doi.org/10.1016/j.ygcen.2010.07.004

Sobczak-Filipiak M, Szarek J, Czopowicz M, Mieczkowska J, Lechowski R (2014). Hepatic stellate cells in the liver of dogs with steroid-induced hepatopathy. Bull. Vet. Inst. Pulawy, 58: 273-276. https://doi.org/10.2478/bvip-2014-0041

Stokes JE, Forrester SD (2004). New and unusual causes of acute renal failure in dogs and cats. Vet. Clin. Small Anim. Pract., 34(4): 909-922. https://doi.org/10.1016/j.cvsm.2004.03.006

Tinted N, Pongcharoenwanit S, Ongvisespaibool T, Wachirodom V, Jumnansilp T, Buckland N, Assawarachan SN (2023). Serum Bile Acids Concentrations and Liver Enzyme Activities after Low-Dose Trilostane in Dogs with Hyperadrenocorticism. Animals, 13(20): 3244. https://doi.org/10.3390/ani13203244

Trivedi NP, Rawal UM (2001). Hepatoprotective and antioxidant property of Androgrphis paniculata (Neem) in BHC induced liver damage in mice. Indian J. Exp. Biol., 36: 41-46.

Villar D, Buck WB, Gonzalez JM (1998). Ibuprofen, aspirin and acetaminophen toxicosis and treatment in dogs and cats. Vet. Hum. Toxicol., 40(3):156-62.

Yadav R, N Yadav, MD Kharya (2016). Immunomodulation potential of Andrographis Paniculata and Tinospora Cordifolia methanolic extracts in combination forms. Int. J. Pharmacol. Res., 6(1): 29-40.

Zhang Y, Wang L, Liu Y (2020). Non-invasive imaging in hepatic steatosis: A comparative evaluation of ultrasound-based modalities. Front. Vet. Sci., 7: 488.