295 - Chlorogenic Acid Represses 5-Fluorouracil Induced Renal Oxidative Stress, Apoptosis and Inflammation in Murine Model

Abstract

5-Fluorouracil (5-FU) is a potent anti-neoplastic agent commonly used for the treatment of various malignancies. But it has varied detrimental effects such as nephrotoxicity, cardiotoxicity etc which limits its widespread clinical practice. Chlorogenic acid (CGA), esterified product of caffeic and quinic acids, is one of the most abundant polyphenol in human diet found in fruits and coffee drinks, possessing an array of biological properties like anti-oxidant, anti-inflammatory and anti-carcinogenic. In the present study, we investigated protective effect of CGA against 5-FU induced nephrotoxicity in wistar rats. The possible mechanism of nephrotoxicity may be ROS induced apoptosis and inflammation via up-regulating ROS generation, P53, bax, caspase-3, TNF-α, cox-2, iNOS, and down regulating Bcl-2. CGA was administered to Wistar rats daily for 20 consecutive days at 60 and 120 mg/kg body weight orally and on day 19, a single intra-peritoneal injection of 150 mg/kg body weight 5-FU was given. CGA ameliorated 5-FU induced LPO, increase in serum toxicity markers and replenished deficit in antioxidant armory. CGA also down regulated apoptotic and inflammatory tissue damage induced by 5-FU. Histological findings further supported biochemical and immunohistochemical results. Therefore results of the present study suggest that CGA may be used in combinational therapy to improve therapeutic index of 5-FU after further preclinical and clinical testing.