Special Issue:

Advancements in Animal Health and Production in Low and Middle-Income Countries

Antioxidant Effect of Cressa cretica Ethanolic Extract against Oxidative Process Induced by Methidathion Pesticide in Male Rats

Methaq A. Abdalsamad*, Zainab J. Mohammed Jawad*

Department of Pathology and Poultry Disease, College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq.

Received | June 28, 2025; Accepted | August 07, 2025; Published | August 15, 2025

*Correspondence | Methaq A. Abdalsamad, Zainab J. Mohammed Jawad, Department of Pathology and Poultry Disease, College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq; Email: [email protected], [email protected]

Citation | Abdalsamad MA, Jawad ZJM (2025). Antioxidant effect of Cressa cretica ethanolic extract against oxidative process induced by methidathion pesticide in male rats. J. Anim. Health Prod. 13(s1): 150-157.

DOI | https://dx.doi.org/10.17582/journal.jahp/2025/13.s1.150.157

ISSN (Online) | 2308-2801

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 key organ that helps mammals with their metabolism and can regenerate itself after losing mass due to exposure to harmful chemicals or infectious agents, as long as the dose is kept within a safe range (Zgheib and Branch, 2017; Al-Dleamy and Jawad, 2022). Chronic exposure to harmful substances or infectious agents, if left untreated, can cause the liver to undergo fibrosis, cirrhosis, and eventually failure (Zgheib and Branch, 2017; Kullak-Ublick et al., 2017).

The excessive and global use of pesticides, particularly in agricultural and public health initiatives, has polluted the environment and had numerous harmful impacts on human and animal health. One of the most prominent groups of pesticides used since the mid-1940s is organophosphate insecticides, also known as OPIs (Joshi and Rajini, 2009). Due to their limited persistence in the mammalian system and relatively low toxicity, OPIs are commonly employed (Khün and Borchert, 2002). The predominant acute mammalian toxicity associated with OPI exposure is muscarinic and nicotinic syndromes, which result from the accumulation of acetylcholine at cholinergic synapses (Khün and Borchert, 2002; Giordano et al., 2007).

Exposure to OPIs, whether chronic or subchronic, can induce oxidative stress, which in turn can generate free radicals and alter the target tissue’s antioxidant or ROS-scavenging enzymes (Seth et al., 2000; Mahmood and Askar, 2022; Mohsen et al., 2024). Cells have several defense mechanisms against oxidative stress, including enzymatic and non-enzymatic antioxidant systems activated by reduced glutathione (GSH) and glutathione-S-transferase (GST), which become unbalanced due to the presence of OPIs (Sefi et al., 2011). According to previous research, dimethyl methidathion was identified as the primary metabolite of methidathion in the livers of rats, and glutathione-S-transferase was found to be the enzyme responsible for its metabolism (Beauvais, 2005). Chronic MD administration also has the potential to alter the histopathology and biochemistry of various organs, including the heart, kidneys, and liver. Nevertheless, antioxidant supplements can help limit oxidative damage (Sutcu et al., 2006; Schmelzer et al., 2013).

Despite this, researchers in Iraq have looked at medicinal plants from over 40 different families that may protect the liver. The plant Cressa cretica L. belongs to the family Convolvulaceae; commonly known as ‘Rudanti’ or ‘Nadewa’ in Hindi is an erect, small, dwarf shrub, that grows in sandy or muddy saline habitats usually in mono-specific stands along the landward edge of marshes and distributed throughout the tropical and sub-tropical regions of the world like India, Timor, and Australia (Western Australia, Northern Territory, Southern Australia, Queensland, New South Wales, Victoria), etc. (Priyashree et al., 2010; Khare et al., 2013; Mutlag et al., 2017).

The phenolic content of the alcoholic extract of Cressa cretica was found to be 99.09±0.10 μg/mg (Pryianka et al, 2015; Ali, 2016). Otherwise, research conducted by Sunita et al. (2011) and Verma et al. (2015) indicates that the plant contains a variety of chemicals, including flavonoids, coumarins, sterols, alkaloids, tannins, glycosides (such as cardiac glycoside and anthraquinone glycoside), protein, carbohydrates, unknown sugars, and a high percentage of salt. Pryianka et al. (2015) also found that the plant has a high content of salt, protein, carbohydrates, flavonoids, and unknown sugars. On the other hand, research by Vite et al. (2012), Khare et al. (2013), and Pryianka et al. (2015) has found that compounds such as cressanyl esters A, B, C, D, E, F, and G can be isolated from the plant’s aerial parts. Leprosy, asthma, diabetes, urinary tract infections, constipation, and enhancement of blood components are some of the traditional uses of the plant. It is also an aphrodisiac, expectorant, stomachic, anti-bilious, tonic, and anthelmintic (Priyashree et al., 2010; Khare et al., 2013). Sudanese people employ the sugar-crusted, dried leaves of Cressa cretica as an emetic, and the plant’s fruits have been reported to have antibacterial and antitubercular properties (Priyashree et al., 2010; Khare et al., 2013). Additionally, Afshari and Zahra (2017) found that specific Cressa cretica fractions had hepatoprotective effects both in vitro and in vivo. Additionally, Afshari and Zahra (2017) found that particular Cressa cretica fractions had a Hepatoprotective impact both in vitro and in vivo.

The study aimed to determine the effect of chronic methidathion (MD) administration on the hepatic integrity of rats and the properties of Cressa cretica alcoholic extract in preventing MD-induced hepatic damage.

Materials and Methods

Chemicals

The methidathion solution is 40% concentrated and comes in a 1-litre box. Made by FABCO-Jordan and sold in local marketplaces for business purposes, the studies employed a commercially available version of MD called Supracide. Additionally, Sigma Chemical Co. (St. Louis, MO) supplied all the other chemicals used in the research.

Plant material

From July to September of 2022, the fresh aerial parts of Cressa cretica L. were gathered at Aljazeera village, Basrah city, Iraq. The Department of Biology at the Science College, University of Basrah, identified and verified the plant.

Preparation of Cressa cretica alcoholic extract

The plant was collected, air-dried, and then ground into a powder, which was placed in tightly sealed receptacles. We use 70% ethanol for extracting the plant using a continuous extraction apparatus (Soxhlet). The extracts were weighed and kept. Samples were kept in closed containers under refrigerated conditions (4°C) (Arabshahi-Delouee and Urooj, 2007; Sabreen et al., 2022).

Phytochemical analysis for Cressa cretica alcoholic extract

1. Detection of flavonoids: The method was performed using magnesium turnings and an Alcoholic potassium hydroxide solution (Alcoholic KOH), as described by Alkhazraji (1991).
2. Detection of Alkaloids: By use of dragendroff reagent. The method was performed according to the protocol described by Tyler et al. (1988).
3. Detection of Glycosides: The method was performed using Benedict’s reagent, as described by Alkhazraji (1991).
4. Detection of Saponins: By use of aqueous mercuric chloride (5%), (HgCl3 5%). The method was performed according to Haddad (1965).
5. Detection of Aldehydes and Ketones: By use of 2.4 2.4-dinitrophenyl hydrazine reagent (Shriner,1980)
6. Detection of terpenoids: By using sulfuric acid and chloroform (Harbone,1984)
7. Detection of phenols: By use of Iron III chloride (FeCl3) ( Trease and Evans, 1989)

Animals and experimental design

Forty-five male Wistar rats (weighing 200–220g) were obtained from the Medical College, Baghdad University. The animals were kept in the same laboratory circumstances for one week to help them adjust to the conditions, which included a 12-hour light and 12-hour dark cycle, a minimum relative humidity of 40%, and a room temperature of 24±2°C. Everyone had unlimited access to the regular diet food and water. Every group of male rats, except Group I, was randomly divided into five equal parts:

• Group I: (5 rats) The control Group was given distilled water
• Group II: (10 rats) 1/10 LD50 MD orally daily for 100 days
• Group III: (10 rats) 1/20 LD50 MD. Orally, daily for 100 days
• Group IV: (10 rats)1/10 LD50 MD + Cressa cretica alcohol extract solution orally daily for 100 days
• Group V: (10 rats) 1/20 LD50 MD + Cressa cretica alcohol extract solution / orally daily for 100 days.

Autopsy scheduled

After the last dose delivery, rats of each group were kept on starvation for 24h, and after that, anaesthetized under mild ether anaesthesia (Al-Rekabi et al., 2021).

Biochemical analysis

Tissue preparation

After the rats were euthanized and their livers harvested, the organs were mixed with 2 millilitres of a phosphate-buffered saline solution containing 1:2 (weight/volume) tissue and 2 millilitres of PBS, with a pH of 7.4. Homogenates were centrifuged at 10,000 g for 15 min at 4°C, and the resultant supernatant was used to determine malondialdehyde (MDA) and reduced glutathione (GSH) levels (Leila et al., 2017).

An estimation of reduced glutathione

An approach refined by Jollow et al. (1974) from a colorimetric method first described by Ellman (1959) was used to quantify the GSH level in the liver. This method relies on the fact that molecules with sulfhydryl groups react with DTNB [(5, 5-dithiobis-(2-nitrobenzoic acid)] to produce a yellow color. To summarize, before centrifuging the tubes at 2500g for 15 minutes, 0.8 mL of liver supernatant was combined with 0.3 mL of 0.25% sulfosalicylic acid solution. A mixture of 0.01 M DTNB and 0.1 M phosphate buffer (pH 7.4) was added to the supernatant. The last measurement was the absorbance at 412 nm. We expressed the total GSH level as nanomoles of GSH per milligram of protein.

Estimation of malondialdehyde (MDA)

Fifty milligrams of hepatic tissue were frozen in liquid nitrogen and stored at 80°C for later use. The tissue samples were crushed and homogenized, then mixed with PBS (pH 7.4). The collected supernatant was centrifuged at 2,000-3,000 rpm for 20 minutes, and the supernatant was then separated for the ELISA test, as described by Witner et al. (2016).

Histopathological examinations

The liver samples underwent fixation in 10% buffered formalin, followed by processing in xylene and alcohol dilutions, and finally embedded in paraffin blocks. After slicing the tissue at 5-μm intervals, it was routinely stained with hematoxylin and eosin (H and E). After carefully inspecting the mounted slides, they were photographed using a light microscope (Bancroft and Layton, 2013; Al-Dleamy and Jawad, 2022).

Statistical analysis

The data were expressed as mean ± standard deviation (SD). The data obtained were analyzed using a one-way analysis of variance (ANOVA) with SPSS software version 20. A one-way ANOVA was used to evaluate the difference in the mean values of the samples and the control (Petrie and Watson, 2013).

Results

Phytochemical analysis for Cressa cretica Alcoholic extract

The phytochemical analysis of Cressa cretica Alcoholic extract revealed the presence of flavonoids, phenols, glycosides, aldehydes, ketones, and triterpenoids, as shown in Table 1.

 

Table 1: Phytochemical analysis for Cressa cretica alcoholic extract.

Chemical constituents	Flavonoids	Phenols	Alkaloids	Glycosides	Aldehydes and ketones	Triterpenoids
Results	+ ++	+++	++	+	+	+

 

Biochemical parameters

Table 2 represents the results of biochemical parameters (MDA and GSH Levels in control and treated groups. As shown in Table 2 there is significant increase (P≤ 0.05) in MDA levels between Group II and Group III when compared with control group; while when treated with alcoholic extract of Cressa cretica the results are showed significant decrease (P≤ 0.05) in MDA levels between Group IV and Group V when compared with Group I. Additionally, the levels of GSH are presented in Table 2 according to results, there is a significant decrease (P≤ 0.05) in GSH levels in groups II and III compared with group I. In contrast, when combined with Cressa cretica alcoholic extract for 100 days, the results showed a significant increase (P ≤ 0.05) in GSH levels between Groups IV and V compared with Group I.

 

Table 2: Results of Biochemical parameters (MDA and GSH ) in experimental rats through antioxidants defense ( Group I: as the control, Group II: rats were administered at a dose of 1/10 LD50 of methidathion, Group III: rats were administered methidathion at a dose of 1/20 LD50, Group IV: Rats were administered (MD 1/10 LD50 + Cressa cretica alcohol extract solution) and Group V: Rats were administered( methidathion at a dose of 1/20 LD50 + Cressa cretica alcohol extract solution).

Parameters groups	MDA ng/ml Mean+SD	GSH ng/ml Mean+SD
Group I ( Control )	C 43.79±3.69	A 0.8692±0.0775
Group II ( LD50 1/10MD)	A 95.26±11.7	C 0.5225±0.0801
Group III (LD50 1/20MD)	A 90.66±10.28	C 0.5857±0.048
Group IV (LD50 1/10 + Extract)	B 70.28±6.37	0.7057±0.0747
Group V( LD50 1/20 + Extract)	B 63.75±5.16	B 0.7532±0.0729
P-Value	0.00021	0.00004
Significant	Sign.	Sign.

 

Different letters refer to a significant difference at (p≤ 0.05).

 

Histopathological study

The liver of the control group had a regular histological structure with a characteristic pattern of hexagonal lobules (Figure 1). The chronic administration in rats treated with MD for one hundred days led to mononuclear cell infiltration, necrosis, dilation of sinusoids and vascular congestion as well as hydropic degeneration and hyperplasia of hepatic tissue in variant degrees in groups (II and III), while the pathological readings were lower than in the MD groups (II and III) when combination of Cressa cretica alcoholic extract with MD in rats after five minutes for one hundred days (groups V and IV). The above pathological features were scored as (-) in Group I and extremely severe (++++) in Group II. At the same time, in Group III, the scoring was severe (+++), as shown in Figure 3; in Group IV, it was moderate (++), as shown in Figure 4; and in Group V, it was mild (+), as shown in Figure 5, according to Leila et al. (2015).

 

Table 3: Semiquantitave scoring of histopathological features changes in liver sections of five groups of rats (Group I (control), Group II(1/10 LD50 MD ), Group III(1/20 LD50 MD ), Group IV(1/10 LD50 MD + Cressa cretica alcoholic extract), Group V(1/20 LD50 MD + Cressa cretica alcoholic extract) after one hundred days (Leila et al., 2015).

Pathological features	Groups
	Group I	Group II	Group III	Group IV	Group V
Mononuclear cell infiltration	_	++++	+++	++	+
Hepatic hemorrhage	_	++++	+++	++	+
Necrosis	_	++++	+++	++	+
Dilation of the sinusoid	_	++++	+++	++	+
congestion of the central vein	_	++++	+++	++	+
Capillary dilation	_	+++	+++	++	+
Hypertrophy of hepatic cells	_	++++	+++	++	+
Hyperplasia of hepatic cells	_	+++	++	+	_
Collagen deposition	_	_	_	+	++
Vacuolated hepatocyte	_	+++	++	+	+

 

Histopathological section of the liver

 

 

 

 

 

DISCUSSION

Recent research evidence explains that Organophosphate insecticides induce toxic symptoms and an enhanced production of reactive oxygen species (ROS) (Gultekin et al., 2000). According to Altuntas et al. (2003), MDA increases when MD is administered. This is precisely what happened in our current study, where there was an increase in MDA levels in the MD groups with two different concentrations (1/10 LD50 and 1/20 LD50, respectively) compared to the controls, and a decrease in glutathione levels. The MD induces reactive oxygen species (ROS), and subsequent depletion of antioxidant cellular defences can result in disruption of the antioxidant balance in mammalian tissues (Valko et al., 2006; Leila et al., 2015; Ali et al., 2020). MD probably causes an increase in ROS, which in turn encourages a rise in the production of MDA and a reduction in glutathione levels (Gultekin et al., 2000; Leila et al., 2015). Consequently, ROS directly reacts with cell biomolecules, causing damage to lipids, proteins, and DNA, which ultimately leads to cell death. As a result, MD causes organ toxicity (Halliwell and Gutteridge, 2002; Leila et al., 2015). According to the results, there was a decrease in MDA levels and an increase in GSH levels in Cressa cretica alcoholic extract at concentrations of 1/10 LD50 + Cressa cretica alcoholic extract and 1/20 LD50 + Cressa cretica alcoholic extract.

Glutathione reduced is a highly convertible tripeptide, a biological antioxidant that is not enzymatic, and a vital component of the completely antioxidant defense system that protects the hepatic cells’ membrane protein thiols from the adverse effects of reactive oxygen species (Singh et al., 2014, 2015; Saddam, 2021; Al-Rekabi et al., 2021). However, subsequent dose-dependent retrieval of glutathione has been observed in experimental rats treated with Cressa cretica extract. Based on the results of the phytochemical analysis of the alcoholic extract of the herb, as shown in Table 1 phenols, flavonoids, and glycosides have been identified as present. In accordance with studies by Khare et al. (2013), Thirunavukkarasu et al. (2014), Singh et al. (2015), El-Alfy et al. (2019), and Rusul and Amira (2022). The flavonoids and phenolic compounds have antioxidant activity by scavenging free radicals produced by methidathion. The above findings corroborate the results, which showed that groups receiving a combination of remedies showed decreased MDA levels and increased GSH levels.

Actually, the current study indicates that MD causes several pathological alterations in the liver parenchyma in groups with two different concentrations (1/10 LD50 and 1/20 LD50). The liver sections of the MD-treated group showed multiple focal necrotic areas surrounding the portal area and the central vein, with or without infiltration of inflammatory cells. These findings may be due to the adverse effects of reactive oxygen species generated by methidathion, which destroy components of the liver membrane. This was confirmed by studies conducted by researchers (Gokalp et al., 2003; Kalender et al., 2010; Sutcu et al., 2006; Leila et al., 2015). However, the histological changes caused by MD chronic administration were moderate when Cressa cretica alcoholic extract was administered in combination with MD groups ( II and III groups,1/10 LD50 + Cressa cretica alcoholic extract and 1/20 LD50 + Cressa cretica alcoholic extract) of degeneration and necrosis with inflammatory cell infiltration as well as fatty changes in some of the hepatocytes were seen in the section of hepatic tissue of the group protected with Cressa cretica in both groups (1/10 LD50 + Cressa cretica alcoholic extract and 1/20 LD50 + Cressa cretica alcoholic extract) in respectively as compared to the controls groups.

The results of the current study showed that alcohol extracts of the herb contained flavonoids and phenol compounds. Flavonoids are known to be vascular protectors and have been found to have hepatoprotective properties, acting to reduce hepatic bleeding induced by MD. This was demonstrated by Kumar et al. (2009), Shihab et al. (2011) and Ibraheem et al. (2018). The flavonoids and phenols may aid in preventing oxidative processes and help restore hepatic tissue. However, the presence of active principles in the plant extract, particularly flavonoids and phenolic compounds, may be responsible for the protective and antioxidant properties of Cressa cretica.

Conclusion

The current study’s findings showed that the extract from Cressa cretica had a free radical scavenging action against the chronic toxic effect of methidathion. The polyphenolic and flavonoid compounds, as well as other phytochemical elements, in the Cressa cretica extract may be responsible for its overall antioxidant action. According to the current study’s findings, Cressa cretica may be a valuable natural antioxidant source that could be utilised as a therapeutic agent to prevent or slow the development of reactive oxygen species and related degenerative disorders caused by oxidative stress.

ACKNOWLDGEMENTS

We acknowledge the support of time and facilities from Pathology and Poultry Disease Department, University of Baghdad for this study.

NOVELTY STATEMENT

This study introduces a novel approach by the alcoholic extract of leave’s Cressa cretica in preventing hepatic damage induced by chronic administration of Methidathion pesticide in male rats.

AUTHOR’S CONTRUBUTION

The experiment was conceived and designed by Zainab Jamal. The experimental work and the data were conducted by Methaq. Every author examined and gave their approval to the manuscript final draft.

Ethical statement

The Scientific Committee of the Department of Pathology, College of Veterinary Medicine, University of Baghdad, and the local Committee for Animal Care and Use at the same institution in Baghdad, Iraq, examined and approved the study’s design and methods in compliance with ethical standards about the treatment of animals dated April 20, 2022.

Conflict of interest

The authors have declared no conflict of interest.

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