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The Effects of Cimetidine, Ranitidine and Famotidine on Cisplatin-Induced Nephrotoxicity in male rats

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Year: 2019
COI code: TOXICOLOGY15_169
Paper Language: English

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Authors The Effects of Cimetidine, Ranitidine and Famotidine on Cisplatin-Induced Nephrotoxicity in male rats

  Zahra Honarpishehfard - Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz Iran
  Akram Jamshidzadeh - Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz Iran
  Reza Heidari - Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz Iran- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz Iran
  SamiraSadat Abolmaali - Department of Pharmaceutical Nanotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
  Sepideh Alidaei - Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz Iran

Abstract:

Cisplatin is a chemotherapy drug that treats a wide range of solid tumors. However, its clinical use is due to renal failure and a reduction in glomerular clearance of 15 to 30% of patients are limited. Several mechanisms that contribute to cisplatin in kidney dysfunction include the damage to tubular epithelial cells, shrinkage in small kidney vessels, and an increase in the incidence of pre-inflammatory cytokines. The accumulation of cisplatin in the kidney and the resulting renal damage depends on the amount of cisplatin renal secretion through the multidrug and toxin protein 1 (MDR1) and (oct2) organic cation transporter2. Cimetidine, an antagonist of H2 histamine, by controlling the OCT transporter, effectively eliminates or reduces the effects of cisplatin induced auto-toxicity and nephrotoxicity. Considering the fact that in many chemotherapy protocols today, cisplatin is used and due to the prevalence of kidney failure and the importance of its prophylactic measures, this study to investigate the effects of the improvement of the cimetidine, ranitidine and famotidine drugs on the damage to the kidney system was at the same time as cisplatin. This study examined the impact of cimetidine, Ranitidin and Famotidine supplementation on kidney as a major targets of cisplatin -induced toxicity. Ratsreceived cisplatin+cimetidine (50،100 mg/kg) ،cisplatin+ Ranitidin (25،50 mg/kg) and cisplatin+ famotidine (20 mg/kg). Blood and kidney samples were collected at scheduled time interval. Serum biomarkers, along with markers of oxidative stress in the kidney tissue was evaluated. Cisplatin toxicity was evident in rats as a significant elevation in markers of oxidative stress. Kidney injury was histopathologically evident by inflammation and hemorrhage. Furthermore, high level of reactive oxygen species (ROS), lipid peroxidation (LPO), depleted glutathione reservoirs, and impaired tissue antioxidant capacity were also detected in the kidney of that rats received cisplatin. However, cimetidine, Ranitidin and Famotidine supplementation decreased ROS, and LPO. Meanwhile, it was found that cimetidine, ranitidin and famotidine supplementation attenuated oxidative stress markers in the kidney of treated animals with cisplatin. Moreover, kidney histopathological changes were markedly mitigated by cimetidine, ranitidin and famotidine treatment. The mechanisms for the beneficial effects of cimetidine, ranitidin and famotidine administration in treated animals might be linked to its ability for preserving cellular redox environment, preventing oxidative stress.

Keywords:

Renal impairment, cisplatin, cimetidine, ranitidine and famotidine

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COI code: TOXICOLOGY15_169

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Honarpishehfard, Zahra; Akram Jamshidzadeh; Reza Heidari; SamiraSadat Abolmaali & Sepideh Alidaei, 2019, The Effects of Cimetidine, Ranitidine and Famotidine on Cisplatin-Induced Nephrotoxicity in male rats, 15th iranian congress of toxicology, تهران, دانشگاه علوم پزشكي شهيد بهشتي, https://www.civilica.com/Paper-TOXICOLOGY15-TOXICOLOGY15_169.htmlInside the text, wherever referred to or an achievement of this article is mentioned, after mentioning the article, inside the parental, the following specifications are written.
First Time: (Honarpishehfard, Zahra; Akram Jamshidzadeh; Reza Heidari; SamiraSadat Abolmaali & Sepideh Alidaei, 2019)
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Paper No.: 2097
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