Ameliorative Effect of Gallic Acid on Cyclophosphamide-Induced Oxidative Injury and Hepatic Dysfunction in Rats.

Ebenezer Tunde Olayinka,Ayokanmi Ore,Olaniyi Solomon Ola,Oluwatobi Adewumi Adeyemo

doi:10.3390/medsci3030078

Ebenezer Tunde Olayinka, Ayokanmi Ore + Show 2 more

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https://doi.org/10.3390/medsci3030078

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Journal: Medical Sciences	Publication Date: Sep 8, 2015
Citations: 36	License type: CC BY 4.0

Affiliation: Ajayi Crowther University

Abstract

Cyclophosphamide (CP), a bifunctional alkylating agent used in chemotherapy has been reported to induce organ toxicity mediated by generation of reactive oxygen species and oxidative stress. Gallic acid (GA), a phenolic substance, is a natural antioxidant with proven free radical scavenging activity and offers protection against oxidative damage. This research study was designed to investigate the ameliorative effect of GA against CP-induced toxicity in rats. Twenty-five male Wistar rats (180–200 g) were randomized into five treatment groups: (A) control, (B) CP, 2 mg/kg body weight (b.w.), (C) pre-treatment with GA (20 mg/kg b.w.) for seven days followed by CP (2 mg/kg b.w.) for seven days, (D) co-treatment with GA (20 mg/kg b.w) and CP (2 mg/kg b.w.) for seven days, and (E) GA (20 mg/kg b.w.) for seven days. CP induced marked renal and hepatic damages as plasma levels of urea, creatinine, bilirubin and activities of AST, ALT, ALP and GGT were significantly elevated (p < 0.05) in the CP-treated group relative to control. In addition, hepatic levels of GSH, vitamin C and activities of SOD, catalase and GST significantly reduced in the CP-treated group when compared with control. This was accompanied with a significant increase in hepatic lipid peroxidation. The restoration of the markers of renal and hepatic damages as well as antioxidant indices and lipid peroxidation by pre- and co-treatment with GA clearly shows that GA offers ameliorative effect by scavenging the reactive oxygen species generated by CP. This protective effect may be attributed to the antioxidant property of gllic acid.

Highlights

Cyclophosphamide (CP), Figure 1a, is a synthetic alkylating agent chemically related to the nitrogen mustards [1] widely used as an anticancer and immunosuppressive drug [2,3] and in the treatment of nephrotic syndrome [4,5]
The toxicities associated with CP have led to an increasing search for effective model compounds that could protect against its induced organ toxicity [17,19,20]
alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) are associated with the cell membrane and their increase in the plasma is an indication of impairment of intrahepatic and extra-hepatic bile flow, hepatobiliary injury and overproduction or leakage of ALP and GGT [60,61]

Summary

Introduction

Cyclophosphamide (CP), Figure 1a, is a synthetic alkylating agent chemically related to the nitrogen mustards [1] widely used as an anticancer and immunosuppressive drug [2,3] and in the treatment of nephrotic syndrome [4,5]. It is effective against a wide spectrum of malignancies, such as, leukemia, lymphoma, breast, lung, prostate, and ovarian cancers [6,7]. The toxicities associated with CP have led to an increasing search for effective model compounds that could protect against its induced organ toxicity [17,19,20]

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