Gallic Acid Mitigates Diclofenac-induced Liver Toxicity by Modulating Oxidative Stress and Suppressing Gene Expression in Male Rats

Overview

Journal Pharm Biol

Specialties Pharmacology
Pharmacy

Date 2020 Jul 8

PMID 32633182

Citations 14

Authors

Mohsen Esmaeilzadeh

Esfandiar Heidarian

Mehrnoosh Shaghaghi

Hoshang Roshanmehr

Mohammad Najafi

Alireza Moradi

Ali Nouri

Affiliations

Soon will be listed here.

Abstract

Context: Diclofenac (DIC) is an NSAID and consumption of this drug creates side effects such as liver injury. Gallic acid (GA), a natural component of many plants, is used as an antioxidant agent.

Objective: This study assesses the hepatoprotective effects of GA in the rat model of DIC-induced liver toxicity.

Materials And Methods: In this research, the male Wistar rats were separated into five groups ( = 6). Group 1, control, received normal saline (1 mL/kg bw, i.p.); Group 2 received DIC-only (50 mg/kg bw, i.p.); Groups 3, received DIC (50 mg/kg bw, i.p.) plus silymarin (100 mg/kg bw, po), groups 4 and 5 received DIC (50 mg/kg bw, i.p.) plus GA (50 and 100 mg/kg, po, respectively).

Results: The data demonstrated that the liver levels of the GSH, GPx, SOD, and CAT significantly reduced and the levels of the serum protein carbonyl, AST, ALP, ALT, total bilirubin, MDA, serum IL-1β, and the liver gene expression were remarkably increased in the second group compared to control group. On the other hand, treatment with GA led to a significant elevation in GSH, GPx, SOD, CAT, and a significant decrease in protein carbonyl, AST, ALP, ALT, total bilirubin, MDA, serum IL-1β, and gene expression of in comparison with the second group. Histological changes were also ameliorated by GA oral administration. The data show that the oral administration of GA could alleviate the noxious effects of DIC on the antioxidant defense system and liver tissue.

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References

Padma V, Sowmya P, Arun Felix T, Baskaran R, Poornima P . Protective effect of gallic acid against lindane induced toxicity in experimental rats. Food Chem Toxicol. 2011; 49(4):991-8. DOI: 10.1016/j.fct.2011.01.005. View

Ellman G . Tissue sulfhydryl groups. Arch Biochem Biophys. 1959; 82(1):70-7. DOI: 10.1016/0003-9861(59)90090-6. View

Mazumdar K, Dutta N, Dastidar S, Motohashi N, Shirataki Y . Diclofenac in the management of E. coli urinary tract infections. In Vivo. 2006; 20(5):613-9. View

Chandrasekharan N, Dai H, Roos K, Evanson N, Tomsik J, Elton T . COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A. 2002; 99(21):13926-31. PMC: 129799. DOI: 10.1073/pnas.162468699. View

Jadon A, Bhadauria M, Shukla S . Protective effect of Terminalia belerica Roxb. and gallic acid against carbon tetrachloride induced damage in albino rats. J Ethnopharmacol. 2006; 109(2):214-8. DOI: 10.1016/j.jep.2006.07.033. View

Mahmoud A, Germoush M, Alotaibi M, Hussein O . Possible involvement of Nrf2 and PPARγ up-regulation in the protective effect of umbelliferone against cyclophosphamide-induced hepatotoxicity. Biomed Pharmacother. 2016; 86:297-306. DOI: 10.1016/j.biopha.2016.12.047. View

Nouri A, Heidarian E, Nikoukar M . Effects of N-acetyl cysteine on oxidative stress and TNF-α gene expression in diclofenac-induced hepatotoxicity in rats. Toxicol Mech Methods. 2017; 27(8):561-567. DOI: 10.1080/15376516.2017.1334732. View

Hafeman D, Sunde R, Hoekstra W . Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. J Nutr. 1974; 104(5):580-7. DOI: 10.1093/jn/104.5.580. View

Sultan M, Ben-Ari Z, Masoud R, Pappo O, Harats D, Kamari Y . Interleukin-1α and Interleukin-1β play a central role in the pathogenesis of fulminant hepatic failure in mice. PLoS One. 2017; 12(9):e0184084. PMC: 5617151. DOI: 10.1371/journal.pone.0184084. View

10.

Laskin D, Laskin J . Role of macrophages and inflammatory mediators in chemically induced toxicity. Toxicology. 2001; 160(1-3):111-8. DOI: 10.1016/s0300-483x(00)00437-6. View

11.

Alabi Q, Akomolafe R . Kolaviron Diminishes Diclofenac-Induced Liver and Kidney Toxicity in Wistar Rats Via Suppressing Inflammatory Events, Upregulating Antioxidant Defenses, and Improving Hematological Indices. Dose Response. 2020; 18(1):1559325819899256. PMC: 7054740. DOI: 10.1177/1559325819899256. View

12.

Harirforoosh S, West K, Murrell D, Denham J, Panus P, Hanley G . Examination of the pharmacodynamics and pharmacokinetics of a diclofenac poly(lactic-co-glycolic) acid nanoparticle formulation in the rat. Eur Rev Med Pharmacol Sci. 2016; 20(23):5021-5031. View

13.

Heidarian E, Rafieian-Kopaei M, Khoshdel A, Bakhshesh M . 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. 2014; 4(Suppl 1):S429-35. PMC: 4025298. DOI: 10.12980/APJTB.4.2014C474. View

14.

Gawel S, Wardas M, Niedworok E, Wardas P . [Malondialdehyde (MDA) as a lipid peroxidation marker]. Wiad Lek. 2005; 57(9-10):453-5. View

15.

Pang L, Ye W, Che X, Roessler B, Betz A, Yang G . Reduction of inflammatory response in the mouse brain with adenoviral-mediated transforming growth factor-ss1 expression. Stroke. 2001; 32(2):544-52. DOI: 10.1161/01.str.32.2.544. View

16.

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

17.

Bjornsson E . Hepatotoxicity by Drugs: The Most Common Implicated Agents. Int J Mol Sci. 2016; 17(2):224. PMC: 4783956. DOI: 10.3390/ijms17020224. View

18.

Omobowale T, Oyagbemi A, Ajufo U, Adejumobi O, Ola-Davies O, Adedapo A . Ameliorative Effect of Gallic Acid in Doxorubicin-Induced Hepatotoxicity in Wistar Rats Through Antioxidant Defense System. J Diet Suppl. 2017; 15(2):183-196. DOI: 10.1080/19390211.2017.1335822. View

19.

Al-Dossari M, Fadda L, Attia H, Hasan I, Mahmoud A . Curcumin and Selenium Prevent Lipopolysaccharide/Diclofenac-Induced Liver Injury by Suppressing Inflammation and Oxidative Stress. Biol Trace Elem Res. 2019; 196(1):173-183. DOI: 10.1007/s12011-019-01910-4. View

20.

Elgebaly H, Mosa N, Allach M, El-Massry K, El-Ghorab A, Al Hroob A . Olive oil and leaf extract prevent fluoxetine-induced hepatotoxicity by attenuating oxidative stress, inflammation and apoptosis. Biomed Pharmacother. 2017; 98:446-453. DOI: 10.1016/j.biopha.2017.12.101. View