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Mitigation of azathioprine-induced oxidative hepatic injury by the flavonoid quercetin in wistar rats
- Source :
- Toxicology mechanisms and methods. 18(8)
- Publication Year :
- 2009
-
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.
- Subjects :
- chemistry.chemical_classification
biology
Health, Toxicology and Mutagenesis
Glutathione peroxidase
Glutathione reductase
Aspartate transaminase
Glutathione
Pharmacology
Toxicology
Malondialdehyde
medicine.disease_cause
Lipid peroxidation
chemistry.chemical_compound
Biochemistry
chemistry
Alanine transaminase
medicine
biology.protein
Oxidative stress
Subjects
Details
- ISSN :
- 15376524
- Volume :
- 18
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Toxicology mechanisms and methods
- Accession number :
- edsair.doi.dedup.....79c1b6550e10aeca3e32ac5dfafe40b9