Antioxidants attenuate glycerol-endotoxin induced acute renal failure in rats

Sepsis sometimes occurs in traumatic rhabdomyolysis; however, the possibility that injection of endotoxin from Gram-negative bacteria may affect the severity of renal injury during rhabdomyolysis has not been directly examined. The aims of this study were: (i) to examine whether injection of glycerol, which causes rhabdomyolysis, simultaneously with a low dose of endotoxin will result in acute renal failure (ARF) in the rat; and (ii) whether this injury is due to the increased formation of free oxygen radicals. Therefore, a low dose of glycerol (0.375 ml/100 g), which does not cause acute renal failure, and endotoxin at a dose that does not cause renal injury (0.0375 mg/100 g) were simultaneously injected. The extent of renal injury was examined 24 h after the simultaneous injection of these two substances. The parameters measured included creatinine, BUN, urine volume, RPF, GFR, percent absorption of sodium and potassium as well as arterial blood pressure. In order to examine whether renal injury due to the combination of glycerol and endotoxin results from free oxygen radicals, DMTU (50 mg/100 g), SOD (8 mg/100 g) and vitamin E (2 mg/kg each day for 7 days) were injected. Acute renal failure was induced by the simultaneous injection of glycerol and endotoxin. Treatment with DMTU or vitamin E significantly reduced renal injury and returned the values of the measured parameters to their control values. The antioxidant SOD also reduced the renal injury; however, with this antioxidant the reduction was less pronounced and the measured parameters did not return to their control values. This study indicates that the severity of renal injury during rhabdomyolysis may increase if endotoxin is present in the body. Furthermore, this study indicates that this increased renal injury may be due to free oxygen radicals. Traumatic rhabdomyolysis is a frequent cause of ARF. Therefore, it is important to create an experimental model that will also include actual possibilities, such as sepsis, which have not been taken into consideration to date.