Effects of Pretreatment With Single-Dose or Intermittent Oxygen on Cisplatin-Induced Nephrotoxicity in Rats

BACKGROUND: Renal injury is the main side effect of cisplatin (CP), an anticancer drug. It has been shown that pretreatment with single-dose oxygen (0.5 to six hours) could reduce CP-induced renal toxicity in rats. OBJECTIVES: The present study aimed to compare the effects of pretreatment with single-dose and intermittent O(2) on CP-induced nephrotoxicity. MATERIALS AND METHODS: Adult male rats were allocated to seven groups (eight rats in each group). The rats were kept in normal air or hyperoxic environment (O(2), 80%) for either a single six-hour period or intermittent six hours per day for seven days and then were subjected to intraperitoneal injection of saline or CP (5 mg/kg) at 48 hours, 72 hours, or seven days after exposure to O(2). Three days after CP (or Saline) injection, renal function tests, renal tissue injury scores, and cleaved Caspase-3 and Bax/Bcl-2 genes expression (as markers of renal cell apoptosis) were assessed. RESULTS: Treatment with the 6-hour single-dose O(2) reduced renal injury significantly when CP was administrated 48 hours after O(2) pretreatment. Pretreatment with intermittent seven days of six hours per day had no protective effects and even relatively worsened renal injury when CP was injected 48 hours or 72 hours after the last session of O(2) pretreatment. The beneficial effects of pretreatment with O(2 )on renal structure and function were seen if CP was administrates seven days after pretreatment with intermittent O(2). CONCLUSIONS: The pattern of pretreatment with O(2) could change this potential and highly protective strategy against CP-induced nephropathy to an ineffective or even mildly deteriorating one. Therefore, O(2) administration before CP injection to patients with cancer, for therapeutic purposes or as a preconditioning approach, should be performed and investigated with caution until exact effects of different protocols has been determined in human.