BETTERMENT OF DICLOFENAC-INDUCED NEPHROTOXICITY BY PENTOXIFYLLINE THROUGH MODULATION OF INFLAMMATORY BIOMARKERS

  • HAYDER M. AL-KURAISHY Department of Clinical Pharmacology, Medicine and Therapeutics, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq.
  • ALI I. AL-GAREEB Department of Clinical Pharmacology, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq.
  • NAWAR RAAD HUSSIEN Department of Clinical Pharmacology, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq.

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.

Keywords: Nephrotoxicity, Diclofenac, Pentoxifylline.

References

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AL-KURAISHY, H. M., A. I. AL-GAREEB, and N. R. HUSSIEN. “BETTERMENT OF DICLOFENAC-INDUCED NEPHROTOXICITY BY PENTOXIFYLLINE THROUGH MODULATION OF INFLAMMATORY BIOMARKERS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 3, Feb. 2019, pp. 433-7, https://innovareacademics.in/journals/index.php/ajpcr/article/view/30829.
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