Abstract
Objectives: Diclofenac-induced nephrotoxicity is caused by oxidative stress which leads to lipid peroxidation and formation of free radicals. Pentoxifylline can ameliorates renal tissue injury by its anti-inflammatory, antifibrotic, and antioxidant effects, so it mitigates the progression of renal diseases. Therefore, the aim of this study was to evaluate the nephroprotective effects of pentoxifylline on diclofenac-induced nephrotoxicity in rats.
 Methods: A total of 30 male Sprague-Dawley rats were allocated into three groups, Group 1 (n=10): Rats treated with distilled water 5 ml/kg plus normal saline 5 ml/kg for 12 days, Group 2 (n=10): Rats treated with distilled water 5 ml/kg plus diclofenac 15 mg/kg for 12 days, and Group 3 (n=10): Rats treated with pentoxifylline 100 mg/kg plus diclofenac 15 mg/kg for 12 days. Blood urea, creatinine, malondialdehyde (MDA), superoxide dismutase (SOD-1), glutathione reductase (GSH), neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecules (KIM-1) vitronectin (VTN), integrin (ITG) , interleukin-18 (IL-18) and cystatin-C were used to measure the severity of nephrotoxicity.
 Results: Diclofenac-induced nephrotoxicity led to significant elevation in blood urea, serum creatinine, MDA, IL-18, KIM-1, NGAL, serum ITG, and VTN with decrease of SOD-1 and GSH sera levels p<0.05. Treatment with pentoxifylline showed no significant effect on all biomarker levels compared to diclofenac group except on serum level KIM-1 and serum VTN, p<0.05.
 Conclusion: Pentoxifylline produced significant nephroprotective effect on diclofenac-induced nephrotoxicity through modulation of inflammatory biomarkers.
Highlights
Nephrotoxicity is a renal-specific situation in which the toxic metabolites do not excrete normally due to toxic agents and drugs [1]
Acute interstitial nephritis is caused by nonsteroidal anti-inflammatory drug (NSAIDs) and rifampicin, while chronic interstitial nephritis is caused by lithium and calcineurin inhibitors [2]
During diclofenac-induced nephrotoxicity, rat body weight was increased to 286.87±27.24 g compared to the control group 268.00±25.01g but not significant, p=0.20
Summary
Nephrotoxicity is a renal-specific situation in which the toxic metabolites do not excrete normally due to toxic agents and drugs [1]. Nephrotoxic agents lead to interstitial nephritis and glomerulonephritis. Acute interstitial nephritis is caused by nonsteroidal anti-inflammatory drug (NSAIDs) and rifampicin, while chronic interstitial nephritis is caused by lithium and calcineurin inhibitors [2]. Proximal renal tubular cells are susceptible to the toxic effect of different drugs and agents due to extended exposure and reabsorbing process. Nephrotoxic drugs lead to damage of the proximal renal tubules through stimulation of oxidative stress, impairments of mitochondrial functions, and interfering with reabsorbing tubular transport process [3]. Diclofenac is a NSAID belongs to the structural family of acetic acid derivatives. Diclofenac is used as analgesic, anti-inflammatory, and antipyretic agent [4]
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