Pretreatment with Oxygen Protects Rat Kidney from Cisplatin Nephrotoxicity

Abstract

Cisplatin (CP) nephrotoxicity is mainly due to reactive oxygen species. Oxygen pre-exposure as a mild oxidative stress may enhance some endogenous defense mechanisms, so its effect on cisplatininduced acute renal failure was investigated in present study.Twenty-four rats were divided into four groups. The O 2 + CP and Air + CP groups were were subjected to i.p. injection of 5 mg/kg cisplatin, and in the Air + Saline and O 2 + Saline groups, saline was injected instead of cisplatin. O 2 + CP and O 2 + Saline groups were pretreated with oxygen (3h/d for two days), and the other two groups were pretreated with room air. Cisplatin was administered 24 h after last pretreatment session. Three days after cisplatin injection, plasma samples were obtained, and parts of kidney tissue were frozen for biochemical analysis or fixed in formalin for histological assessments. Preconditioning with oxygen prior to cisplatin administration led to reduced tubular necrosis and luminal cast formation and improvement of renal function, as was evidenced by significant reduction in plasma creatinine and urea levels. Oxygen pretreatment also significantly reversed cisplatin-induced reduction in renal catalase activity and glutathione level. It could be concluded that oxygen pretreatment could have a delayed protective effect against cisplatin nephrotoxicity, and that increased renal catalase activity may be involved in this protective effect of hyperoxia.

Cisplatin toxicity reduced in human cultured renal tubular cells by oxygen pretreatment

“…6,12,13 The present study demonstrates that this beneficial effect of oxygen pretreatment also is present in human renal tubular cells. Previously proposed mechanisms which could also explain somewhat the present study findings, is that sub-lethal excess amount of free radicals produced during oxygen pretreatment 29 may act as a mediator for induction of cellular protective agents like antioxidant enzymes, 13 heat shock proteins (Wahhabaghai et al, unpublished data) and probably other endogenous defense mechanisms.…”

“…3,4 Numerous attempts have been made to decrease CP nephrotoxicity, and several substances shown to be protective in cell culture also were found to protect the kidney from damage in vivo. [5][6][7] Many studies support the concept that previous renal injury may protect the kidney against a second insult, and it has been shown that the primary stimulus should not necessarily reach the damage level. 6,8 For example, sub-lethal short ischemic periods may decrease subsequent renal functional or structural injury stimulated by prolonged ischemia.…”

“…[5][6][7] Many studies support the concept that previous renal injury may protect the kidney against a second insult, and it has been shown that the primary stimulus should not necessarily reach the damage level. 6,8 For example, sub-lethal short ischemic periods may decrease subsequent renal functional or structural injury stimulated by prolonged ischemia. 9,10 Cisplatin causes significant oxidant loading to the kidney epithelial cells through free radical formation and also damage to antioxidant defense systems and this oxidative stress explains at least partially cytotoxic effects of this drug on renal tubular cells.…”

“…3,11 Previous animal studies have shown that short-term pretreatment with nearly pure oxygenwithout closing to the oxygen toxicity threshold-could lead to some degrees of protection against Cisplatin induced nephrotoxicity and both renal and cardiac ischemic damages. 6,[12][13][14][15] This protective effect may be due to stimulating the endogenous defense mechanisms such as antioxidant systems against free radicals by mild hyperoxia-induced oxidative stress.…”

Normobaric hyperoxia preconditioning ameliorates cisplatin nephrotoxicity

“…9 On the other hand, some evidences suggest that exposure to oxygen prior to Cisplatin therapy may reduce the Cisplatininduced nephrotoxicity in animal model. 10,11 Hypoxia and mitochondrial injury are also implicated in Cisplatin nephrotoxicity. 7 According to our literature review, there is no clinical human study in terms of impact of oxygen therapy before Cisplatin administration on kidney injury.…”