Mitigation of Azathioprine-Induced Oxidative Hepatic Injury by the Flavonoid Quercetin in Wistar Rats

Abstract

Azathioprine (AZA), one of the widely prescribed immunosuppressant drugs in organ transplantation and autoimmune diseases, could cause hepatotoxicity in the course of therapy. The current work was designed to assess the protective role of the dietary flavonoid, quercetin (QE), in oxidative hepatic damage induced by AZA. Adult male Wistar rats were divided into four treatment groups. Two groups were treated with single intraperitoneal injection of AZA (50 mg/kg body weight); one of these groups was pretreated with QE (50 mg/kg body weight) intraperitoneally once a day for 7 days. A vehicle treated control group and a QE control group were also included. Hepatotoxicity, evident from increased levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma glutamyl transpeptidase (GGT) in serum 24 h after AZA treatment, was significantly (p < 0.05) normalized by QE pretreatment. AZA administered rats displayed declined levels of endogenous antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH)], along with elevated levels of malondialdehyde (MDA). However, pretreatment with QE significantly precluded lipid peroxidation and maintained the activities of antioxidant defenses at a near normal status. Besides, AZA induced oxidative stress and subsequent DNA damage was effectively manifested by QE, which was confirmed by agarose gel electrophoresis. These findings highlight the salubrious effect of QE as a hepatoprotectant in AZA-induced oxidative stress mediated hepatic injury.

A systematic review on hepatoprotective activity of quercetin against various drugs and toxic agents: Evidence from preclinical studies

“…AZA administered rats displayed declined levels of SOD, catalase (CAT), GPx, glutathione reductase (GR), and GSH along with elevated levels of MDA. However, pretreatment with QE significantly precluded lipid peroxidation and maintained the activities of antioxidant defenses at a near normal status (Shanmugarajan et al, ).…”

Possible Synergistic Effect and Antioxidant Properties of Chitosan Nanoparticles and Quercetin against Carbon Tetrachloride-Induce Hepatotoxicity in Rats

“…The in vivo study revealed that the protective role of chitosan nanoparticle alone or in combination with quercetin against oxidative stress and hepatotoxicity induced by carbon tetrachloride in rat model was evaluated. The selected doses of CCl 4 , chitosan nanoparticles and quercetin were literature based [68]- [70], respectively). In the current study, treatment with CCl 4 induced severe hepatotoxicity and oxidative stress as well as histological changes typical to those reported in the literature.…”

Mitochondrial and immunoallergic injury increase risk of positive drug rechallenge after drug-induced liver injury: A systematic review

“…2 The key mechanisms of azathioprine liver injury include hypersensitivity, 2 glutathione depletion, oxidative stress with resultant mitochondrial impairment, and depletion of mitochondrial glutathione, 42 ATP, and lipid peroxidation. 43 Nucleoside Reverse-Transcriptase Inhibitors. Positive rechallenge events with nucleoside reverse-transcriptase inhibitors generally resulted in asymptomatic hepatocellular injury in a retrospective series.…”