Effects of Different Doses of Hyperbaric Oxygen on Cisplatin-Induced Nephrotoxicity

Abstract

Cisplatin, an effective antineoplastic agent, frequently induces acute renal failure in animals and humans. Hyperbaric oxygen (HBO) has been shown to prevent cisplatin-induced nephrotoxicity in rats. This study investigated the effect of two different HBO regimes on renal functions, oxidative stress, and histopathological changes in rat kidneys after cisplatin treatment. Wistar rats were divided into five groups: control, HBO, cisplatin, cisplatin plus once daily HBO, and cisplatin plus twice daily HBO. Cisplatin was given as a single intraperitoneal dose of 6 mg/kg, and HBO was applied for 60 min at 2.5 atm for six days. HBO alone did not alter any biochemical parameters or histopathological findings compared with the control group. Cisplatin increased serum urea and creatinine levels and caused severe histopathological injury. In addition, cisplatin increased lipid peroxidation and impaired superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in kidney tissue. Once daily HBO after cisplatin treatment slightly reduced serum urea and creatinine levels and attenuated histopathological injury. HBO also reduced lipid peroxidation and increased SOD and GSH-Px activities significantly. Although twice daily HBO was determined to be more effective than once daily HBO on oxidative stress parameters, it increased serum creatinine levels and histopathological injury compared with the cisplatin group. It was concluded that HBO alone does not induce nephrotoxicity and oxidative stress in rat kidneys; once daily HBO may prevent cisplatin-induced nephrotoxicity, an effect that is partially mediated by the modification

Pathophysiology of Cisplatin-Induced Acute Kidney Injury

“…Generation of reactive oxygen species (ROS), accumulation of lipid peroxidation products in kidneys, and suppressed antioxidant systems are thought to be major mechanisms of cisplatin-induced AKI [117]. Within the cell, cisplatin is converted into a highly reactive form rapidly reacting with thiol-containing antioxidant molecules such as glutathione [20].…”

Oxygenation inhibits ovarian tumor growth by down-regulating STAT3 and cyclin-D1 expressions

“…35 Aydinoz et al 34 reported significant body-weight loss in cisplatin as well as cisplatin + HBO-treated rats. However, the most dramatic weight loss was observed in the cisplatin only-treated group.…”

“…HBO therapy has been investigated as a means by which to prevent cisplatin-mediated nephrotoxicity, 33,34 and otoxicity. 35 Aydinoz et al 34 reported significant body-weight loss in cisplatin as well as cisplatin + HBO-treated rats.…”

Pretreatment with Oxygen Protects Rat Kidney from Cisplatin Nephrotoxicity

“…Therefore, it is not surprising that in Aydinoz's study, daily HBO therapy (for six days) reduced kidney injury but twice daily HBO usage considerably augmented cisplatin-induced ARF. [34] It should be noted that both in Atasoyu and Aydinoz studies, intermittent HBO therapy was started after the cisplatin injection. It could be proposed that short duration pretreatment with oxygen leads to a mild oxidative stress, [11] and this sub-lethal oxidative stress may in turn enhance endogenous defense mechanisms, such as antioxidant molecules and enzymes, against cisplatin-induced free radical injury.…”