Protective effect of pentoxyfilline in renal toxicity after methotrexate administration

Abstract

Introduction: Nephrotoxicity is an important side-effect of treatment with Methotrexate (MTX). Pentoxifylline (PTX) is an anti-inflmmatory and anti-oxidant agent. We hypothesized that pentoxifylline may affords renal protection by downregulating TNF-alpha as well as by improving cellular anti-oxidant activity. Materials and Methods: Forty five male Wistar rats were assigned to 3 groups of 15 animals each: Group 1: control group (0.9% saline). Group 2: MTX; injected with 20 mg/kg MTX intraperitoneally (i.p.). Group 3: MTX+PTX injected i.p. MTX (20 mg/kg) + PTX (50 mg/kg) i.p. PTX was administered since 3 days before MTX administration and continued for 6 days. After 6 days rats were anesthetized and serum sampled and renal tissue removed for biochemical and histological evaluation. Results: Data showed that glutathione peroxidase (GPx), superoxide dismutase (SOD) activities were lower in PTX+MTX group comparing to MTX group significantly (p<0.05). Renal tissue injury index and percent of TUNEL positive cells, renal tissue malondialdehyde (MDA) levels, serum BUN (Blood Urea Nitrogen), creatinine (Cr) and TNF-alpha levels were higher in MTX group comparing to MTX+PTX group significantly (p<0.05). Conclusions: In this study, the increased level of tissue MDA and serum TNF-alpha level together may be suggested that the underlying mechanism is related to direct toxicity of MTX rather than blockage in folate synthesis in kidneys. PTX administration also attenuated renal tissue injury and number of apoptic cells and suppressed the elevation of BUN and Cr levels. However, further studies are essential to elucidate the exact mechanisms of MTX-induced renal toxicity, and protection and the effect of PTX.