Analysis of Tissue Cytokine Levels in Rats with Cisplatin-Induced Experimental Nephrotoxicity
Ramazan Acar1, Nuri Karadurmus1, Bayram Koc21Department of Medical Oncology, Gulhane Training and Research Hospital, Ankara, Turkey, 2Department of Internal Medicine, Gulhane Training and Research Hospital, Ankara, Turkey
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 Sham group (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 cage for one week. Salin solution was administered every 12 hours, starting 36 hours before inducing nephrotoxicity with cisplatin. Body weight and 24-hour urine of rats were followed up in the metabolic cage. The rats were anesthetized with a 5 mg/kg dose of rompun and 100 mg/kg dose of ketamine 84 hours after the cisplatin administration; then, they were sacrificed. Then blood samples were collected from the abdominal aorta and kidney samples were collected to test the levels of tissue antioxidant enzymes. Kidney tissue samples were assigned to two groups. The samples in one group were fixed in formalin and the samples in the other group were fixed in glutaraldehyde. These two group were separately 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-? levels of Group I and Group II were significantly different (p=0.049); however, there were no significant differences in the tissue levels of IL- 1?, 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. Nephrotoxicity is the most important dose-limiting side effect. According to the data obtained from this study, a single high dose of cisplatin in cancer therapy cause kidney injury. It is known that inflammation is one of the majör mechanisms in cisplatin nephrotoxicity and that TNF-? 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-?, which is an inflammatory cytokine. However, there have been no significant changes in the tissue IL-1? 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. Keywords: Cisplatin, cytokine, nephrotoxicity
Cite This Article
Acar R, Karadurmus N, Koc B. Analysis of Tissue Cytokine Levels in Rats with Cisplatin-Induced Experimental Nephrotoxicity. EJMI. 2020; 4(3): 376-379
Corresponding Author: Ramazan Acar