Mitigation of Azathioprine induced Oxidative hepatic injury by the Flavonoid quercetin in wistar rats

26063745, - (2008) Mitigation of Azathioprine induced Oxidative hepatic injury by the Flavonoid quercetin in wistar rats. Masters thesis, Vel’s College of Pharmacy, Chennai.

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Abstract

In the present study, quercetin was taken up for extensive studies to evaluate the hepatoprotective potential against azathioprine induced oxidative liver injury in male Wistar rats. Liver injury was induced in rats by single intraperitoneal injection of AZA (50 mg/kg body weight). It was found that pretreatment with QE for 7 days at a dosage 50 mg/kg body weight through intraperitoneal route was able to reverse most of the deleterious effects in liver induced by AZA. The outcome of this study was summarized below. In this study, the increased levels of marker enzymes and bilirubin in serum after 24 hours of AZA treatment were observed. Administration of QE significantly alleviated the levels of hepatic marker enzymes and bilirubin in the serum of AZA-exposed rats, which infers that the AZA-induced alterations in hepatocellular membrane might have been protected through membrane stabilization effect of QE. An enhancement in lipid peroxidation with a simultaneous depression in the levels of non-enzymatic antioxidant GSH was observed in Wistar rats treated with AZA. QE pretreatment significantly decreased lipid peroxidation and elevate the GSH on AZA exposed rats which reflect the antiperoxidative and antioxidant effect of QE. In the present study the SOD, CAT, GPx and GR enzymes’ levels were decreased in AZA treated group. But the liver antioxidant levels of SOD, CAT, GPx and GR were increased in QE pretreated rats exposed to AZA, which might be due to its free radical scavenging activity of QE. Hepatic nucleic acids (DNA and RNA) and total protein levels depleted significantly in AZA treated rats mainly due to the oxidative damage of hepatic tissue. Pretreatment with QE showed significant protection against decreased hepatic nucleic acids levels and protein by AZA administration. The results of functional tests, together with histological observations, suggest that AZA accumulation leads to serious changes in the histology of the liver, including inflammatory cell infiltration, focal necrosis and sinusoidal dilation, thus imposing a health risk. AZA decreases the GSH level and disturbs the redox state of the cells. The increased formation of lipid peroxides and associated reactive oxygen species leads to a collapse in membrane integrity and other pathological changes in the liver. The antioxidant nature and free radical scavenging activity of QE which would be helpful in protecting the structural integrity of cells, thus, emphasizing the efficacy of QE in reducing the pathological changes and caused by AZA in liver tissue. In addition, the contribution of QE to improving the antioxidant defense could be responsible for the preservation of liver architecture and functions, as indicated by normalization of hepatic markers in AZA administered to QE-treated rats. In conclusion, this study suggests that QE possess the capability to alleviate the AZA-induced oxidative damage in liver, which could be due to its antioxidant nature, which includes free radical scavenging and cell membranes stabilizing properties.

Item Type: Thesis (Masters)
Additional Information: (Reg.No. 26063745)
Uncontrolled Keywords: Mitigation of Azathioprine induced Oxidative hepatic injury by the Flavonoid quercetin in wistar rats
Subjects: PHARMACY > Pharmaceutical Biotechnology
Depositing User: Subramani R
Date Deposited: 03 Oct 2018 15:31
Last Modified: 03 Oct 2018 15:31
URI: http://repository-tnmgrmu.ac.in/id/eprint/9652

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