Analysis of Tissue Cytokine Levels in Rats with CisplatinInduced Experimental Nephrotoxicity

Abstract

Objectives: Analysis of tissue cytokine levels in rats with cisplatin-induced experimental nephrotoxicity.Methods: Twenty Sprague – Dawley male rats were included in the study and assigned to two groups of 10. The Shamgroup (Group I) received a single intraperitoneal (ip) dose of 1 cc saline solution every 12 hours. The cisplatin group(Group II) received a 10 mg/kg ip dose of cisplatin to induce nephrotoxicity. Each group was placed in a metabolic cagefor one week. Salin solution was administered every 12 hours, starting 36 hours before inducing nephrotoxicity withcisplatin. Body weight and 24-hour urine of rats were followed up in the metabolic cage. The rats were anesthetizedwith a 5 mg/kg dose of rompun and 100 mg/kg dose of ketamine 84 hours after the cisplatin administration; then, theywere sacrificed. Then blood samples were collected from the abdominal aorta and kidney samples were collected totest the levels of tissue antioxidant enzymes. Kidney tissue samples were assigned to two groups. The samples in onegroup were fixed in formalin and the samples in the other group were fixed in glutaraldehyde. These two group wereseparately stored in the refrigerator at -80ºC until the time of analysis.Results: The comparison of Group I and two Group II revealed that the levels of urea and creatinine increased significantly (p=0.001 for both parameters), indicating cisplatin-induced nephrotoxicity. Tissue TNF-α levels of Group I andGroup II were significantly different (p=0.049); however, there were no significant differences in the tissue levels of IL1β, IL-10 and IL-6 (p=0.151, p=1, p=0.545; respectively).Conclusion: Cisplatin is one of the most important antineoplastic drugs used for treating solid tumors. Nephrotoxicityis the most important dose-limiting side effect. According to the data obtained from this study, a single high dose ofcisplatin in cancer therapy cause kidney injury. It is known that inflammation is one of the majör mechanisms in cisplatin nephrotoxicity and that TNF-α plays a central role in this development. In the group with cisplatin-induced nephrotoxicity, there has been a significant increase in the tissue levels of TNF-α, which is an inflammatory cytokine. However,there have been no significant changes in the tissue IL-1β and IL-6, both of which are inflammatory cytokines, too. Also,there has not been an increase in the tissue levels of IL-10, which is an anti-inflammatory cytokine.