Antioxidant, anti-inflammatory and protective potential of gallic acid against paraquat-induced liver toxicity in male rats

Document Type : Original Research Article


1 Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

2 Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran


Objective: As a herbicide, paraquat is a toxic agent that has devastating effects on human health. Gallic acid, on the other hand, is a natural compound that its anti-oxidant values have been reported in previous studies. Given these, this study was designed to evaluate whether gallic acid could reduce the toxic effects of paraquat in the liver of rats.
Materials and Methods: Six groups of rats were considered in this study. Group 1 (control group), group 2 (25 mg/kg of paraquat), group 3 (paraquat-plus-silymarin), and groups 4, 5, and 6 (paraquat together with gallic acid at the doses of 25, 50, and 100 mg/kg, respectively). After treatment, biochemical, oxidative, and histopathological parameters were evaluated in the rats.
Results: We found that as compared to the control group, while paraquat reduced the hepatic levels of anti-oxidative compounds such as vitamin C (p<0.001), superoxide dismutase (SOD) (p<0.001), and catalase (CAT) (p<0.001), the toxic agent increased the serum levels of protein carbonyl (PC) (p<0.001), malondialdehyde (MDA) (p<0.05), and IL-1β (p<0.001). Paraquat also increased (p<0.05) both serum lipid profile and liver-associated markers in the rats. Nevertheless, gallic acid not only enhanced (p<0.05) the activity of vitamin C, SOD, and CAT but also remarkably reduced (p<0.05) the serum lipid profile, as well as the oxidative and inflammatory markers in the paraquat-treated rats. Gallic acid had also ameliorating effects on the damaged morphology of hepatocytes upon paraquat treatment.
Conclusion: The results of this study suggested that gallic acid possesses reinforcing effects on the antioxidant defense system and could be administered to reduce the toxicity of paraquat.


Abd El-Rahman N, Kamal El-Dein E, Abd ElHady A, Soliman SM. 2016. Effect of
hesperidin on γ-radiation-and/or paraquat
herbicide-induced biochemical,
hematological and histopathological
changes in rats. Pakistan J Zool, 48: 1407-
Ahmad I, Shukla S, Kumar A, Singh BK,
Kumar V, Chauhan AK, Singh D, Pandey
HP, Singh C. 2013. Biochemical and
molecular mechanisms of N-acetyl cysteine
and silymarin-mediated protection against
maneb-and paraquat-induced hepatotoxicity
in rats. Chem Biol Interact, 201: 9-18.
Akinloye O, Abioye O, Olaojoyetan O,
Awosika O, Akinloye D. 2013. Dosedependent effects of paraquat on c-reactive
protein, some lipid profile parameters and
histology of tissues in male albino rats. Ife J
Sci, 15: 189-195.
Amin F, Memarzia A, Kazerani HR,
Boskabady MH. 2020. Carvacrol and
Zataria multiflora influenced the PPARγ
agonist effects on systemic inflammation
and oxidative stress induced by inhaled
paraquat in rat. Iran J Basic Med Sci, 23:
Amin F, Memarzia A, Rad HK, Kazerani HR,
Boskabady MH. 2021a. Carvacrol and
PPARγ agonist, pioglitazone, affects
inhaled paraquat-induced lung injury in rats.
Sci Rep, 11: 1-15.
Amin F, Roohbakhsh A, Memarzia A, Kazerani
HR, Boskabady MH. 2021b. Immediate and
late systemic and lung effects of inhaled
paraquat in rats. J Hazard Mater, 415: 125-
Effects of gallic acid on paraquat-induced liver toxicity
AJP, Vol. 11, No. 6, Nov-Dec 2021 643
Bradford MM. 1976. A rapid and sensitive
method for the quantitation of microgram
quantities of protein utilizing the principle
of protein-dye binding. Anal Biochem, 72:
Carleton H, Drury R, Wallington E, 1980.
Carleton's histological technique: Oxford
University Press. USA.
El-Rahman A, Kamal El-Dein E, AM AE-H,
Soliman SM. 2016. Effect of hesperidin on
γ-radiation-and/or paraquat herbicideinduced biochemical, hematological and
histopathological changes in rats. Pakistan J
Zool, 48: 1407-1415.
Flohe L, 1984. Superoxide dismutase assays,
Methods in enzymology. Elsevier, pp. 93-
Friedewald WT, Levy RI, Fredrickson DS.
1972. Estimation of the concentration of
low-density lipoprotein cholesterol in
plasma, without use of the preparative
ultracentrifuge. Clin Chem, 18: 499-502.
Gawarammana IB, Buckley NA. 2011. Medical
management of paraquat ingestion. Br J Clin
Pharmacol, 72: 745-757.
Gaweł S, Wardas M, Niedworok E, Wardas P.
2004. Malondialdehyde (MDA) as a lipid
peroxidation marker. Wiad Lek, 57: 453-
Hafez AM. 2009. Antigenotoxic activity of
melatonin and selenium against genetic
damage induced by paraquat. Aust J Basic &
Appl Sci, 3: 2130-2143.
Heidarian E, Nouri A. 2019. Hepatoprotective
effects of silymarin against diclofenacinduced liver toxicity in male rats based on
biochemical parameters and histological
study. Arch Physiol Biochem, 29: 1-7.
Heidarian E, Rafieian-Kopaei M, Khoshdel A,
Bakhshesh M. 2014. Metabolic effects of
berberine on liver phosphatidate
phosphohydrolase in rats fed on high
lipogenic diet: an additional mechanism for
the hypolipidemic effects of berberine.
Asian Pac J Trop Biomed, 4: 429-435.
Heidarian E, Soofiniya Y. 2011. Hypolipidemic
and hypoglycemic effects of aerial part of
Cynara scolymus in streptozotocin-induced
diabetic rats. J Med Plant Res, 5: 2717-2723.
Jadon A, Bhadauria M, Shukla S. 2007.
Protective effect of Terminalia belerica
Roxb. and gallic acid against carbon
tetrachloride induced damage in albino rats.
J Ethnopharm, 109: 214-218.
Karimi-Khouzani O, Heidarian E, Amini SA.
2017. Anti-inflammatory and ameliorative
effects of gallic acid on fluoxetine-induced
oxidative stress and liver damage in rats.
Pharmacol Rep, 69: 830-835.
Koekkoek W, van Zanten AR. 2016.
Antioxidant vitamins and trace elements in
critical illness. Nutr Clin Pract, 31: 457-474.
Nouri A, Heidarian E, Amini-Khoei H,
Abbaszadeh S, Basati G. 2019. Quercetin
through mitigation of inflammatory
response and oxidative stress exerts
protective effects in rat model of diclofenacinduced liver toxicity. J Pharm Pharmacogn
Res, 7: 200-212.
Omaye ST, Turnbull JD, Sauberlich HE, 1979.
Selected methods for the determination of
ascorbic acid in animal cells, tissues, and
fluids, Methods in enzymology. Elsevier,
pp. 3-11.
Omobowale TO, Oyagbemi AA, Ajufo UE,
Adejumobi OA, Ola-Davies OE, Adedapo
AA, Yakubu MA. 2018. Ameliorative effect
of gallic acid in doxorubicin-induced
hepatotoxicity in Wistar rats through
antioxidant defense system. J Diet Suppl,
15: 183-196.
Padma VV, Sowmya P, Felix TA, Baskaran R,
Poornima P. 2011. Protective effect of gallic
acid against lindane induced toxicity in
experimental rats. Food Chem Toxicol, 49:
Priscilla DH, Prince PSM. 2009.
Cardioprotective effect of gallic acid on
cardiac troponin-T, cardiac marker
enzymes, lipid peroxidation products and
antioxidants in experimentally induced
myocardial infarction in Wistar rats. Chem
Biol Interact, 179: 118-124.
Ramezannezhad P, Nouri A, Heidarian E. 2019.
Silymarin mitigates diclofenac-induced
liver toxicity through inhibition of
inflammation and oxidative stress in male
rats. J HerbMed Pharmacol, 8: 231-237.
Reznick AZ, Packer L, 1994. Oxidative damage
to proteins: spectrophotometric method for
carbonyl assay, Methods in enzymology.
Elsevier, pp. 357-363.
Sharifi-Rigi A, Heidarian E, Amini SA. 2019.
Protective and anti-inflammatory effects of
hydroalcoholic leaf extract of Origanum
vulgare on oxidative stress, TNF-α gene
expression and liver histological changes in
paraquat-induced hepatotoxicity in rats.
Arch Physiol Biochem, 125: 56-63.
Sultan M, Ben-Ari Z, Masoud R, Pappo O,
Nouri et al.
AJP, Vol. 11, No. 6, Nov-Dec 2021 644
Harats D, Kamari Y, Safran M. 2017.
Interleukin-1α and Interleukin-1β play a
central role in the pathogenesis of fulminant
hepatic failure in mice. PLoS One, 12:
Wei T, Tian W, Liu F, Xie G. 2014. Protective
effects of exogenous β-hydroxybutyrate on
paraquat toxicity in rat kidney. Biochem
Biophys Res Commun, 447: 666-671.
Wellington K, Jarvis B. 2001. Silymarin: a
review of its clinical properties in the
management of hepatic disorders.
BioDrugs, 15: 465-489.
Wesseling C, De Joode BVW, Ruepert C, León
C, Monge P, Hermosillo H, Partanen LJ.
2001. Paraquat in developing countries. Int
J Occup Environ Health, 7: 275-286.
Winek C. 1986. Drug and chemic