Ultrastructural and Histopathological Analysis of Initial Change and Myoglobin Absorption on Proximal Tubule Injury with Glycerol-induced Rhabdomyolysis in Rats

Rhabdomyolysis is a disorder of striped (skeletal) muscle and is caused by several factors, and acute renal failure associated with myoglobinuria is the most serious complication of rhabdomyolysis. However, the mechanism of tubule damage caused by myoglobin is still unclear. The early histopathological changes were not examined. Myoglobin reabsorption by the proximal renal tubules has not been reported to contribute to cellular damage. We performed histological analysis in a rat rhabdomyolysis model with administration of cytochalasin B (CB), which is an inhibitor of motile cell motile processes. CB inhibits the endocytosis of myoglobin in the proximal renal tubules and the increase in the BUN level, and decreased the percentage of area that had undergone tubular necrosis. On the other hand, initial degenerative changes (shortening of microvilli and protrusion of the cytoplasm) were observed on the cell surface of the proximal tubules with glycerolinduced cellular injury, and were not inhibited by the administration of CB. In conclusion, initial glycerolinduced cellular injury of the renal proximal tubules may be caused by free iron, which is isolated from myoglobin in urine. Further, the combination of the free iron in urine and the myoglobin reabsorbed by tubular cells may lead to cell necrosis.