Effect of Remote Ischemic Preconditioning on Systemic Toxicity and Ototoxicity Induced by Cisplatin in Rats: Role of TNF-α and Nitric Oxide.

BACKGROUND/AIMS: Cisplatin is a chemotherapeutic agent. The use of remote ischemic preconditioning (RIPC) was proposed after the observation that ischemic preconditioning of a cardiac vascular area could protect another completely distinctly.

METHODS: This is an experimental study. Male Wistar rats were anesthetized, and they underwent a hearing evaluation via measurement of the brainstem auditory evoked potential (BSAEP). Then, cisplatin was administered intraperitoneally (IP) at a dose of 8 mg/kg/day for 4 consecutive days to group 1, whereas saline solution was administered IP to group 2. In groups 3 and 4, ischemia of the right hind paw was performed for 10 min, followed by reperfusion for 30 min, after which cisplatin or saline was administered IP to group 3 or group 4, respectively. Afterwards, all animals were evaluated via the BSAEP. The right cochlea was dissected for immunohistochemistry.

RESULTS: RIPC lowered the increase in BSAEP of the animals treated with cisplatin (p = 0.0146). Weight loss decreased in the animals subjected to RIPC (p < 0.005). In group 3, RIPC reversed immunostaining for tumor necrosis factor-α and inducible nitric oxide synthase in the stria vascularis injured by cisplatin (p < 0.05).

CONCLUSION: RIPC protects against systemic toxicity and ototoxicity induced by cisplatin in rats.