Effects of rifampin on renal ischemic/reperfusion in rats: Role of nitric oxide system
Sara Eghbalnia1, Hamed Shafaroodi2 1. Department of Toxicology, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran 2. Department of Pharmacology, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran
Aim: Renal ischemia/reperfusion (I/R) injury is highly associated with morbidity and mortality. Oxidative stress, inflammation, and apoptosis play pivotal roles in the development of renal dysfunction following renal I/R. Rifampin is an antibacterial agent that is widely used in tuberculosis and leprosy therapy. Interestingly, some experimental studies indicate that rifampin acts as a hydroxyl radical scavenger and a glucocorticoid receptor activator. In addition, it has been reported to have neuroprotective effects in in vitro and in vivo models. In the present study we aimed to examine the effects of acute rifampin administration on the renal ischemia/reperfusion injury in rat. Methods: Ischemia/reperfusion injury was induced by bilateral clamping of renal pedicles (45 min) followed by reperfusion (24 h) caused significant renal dysfunction and marked renal injury. The mechanism of rifampin-mediated renoprotection was explored by combined use of rifampin and nitro-L-arginine methyl ester (L-NAME) (non-selective nitric oxide synthase inhibitor). Rifampin-treated animals were given 5, 10 and 20mg/kg rifampin intraperitoneally, 2 hours before ischemia. To investigate the role of nitric oxide and cyclooxygenase pathways in renoprotective effect of rifampin, L-NAME was administered before rifampin injection. Serum creatinine and blood urea nitrogen were assessed after 24 h of reperfusion. Results: Rifampin especially at 10mg/kg preconditioning significantly reduced creatinine and blood urea nitrogen (P<0.05). Administration of L-NAME completely reversed renoprotective effect of rifampin. The results show that a single dose of rifampin significantly improves renal function following ischemia/reperfusion injury. Conclusions: In conclusion, the ability of rifampin to enhance renal function against ischemia/reperfusion injury suggests a potential clinical application in the setting of kidney transplantation. However more detailed investigations are required before any definite conclusion.