Gentamicin nephrotoxicity I. Acute biochemical correlates in rats

Abstract Following acute exposure (1.5 hr) to 100 mg/kg gentamicin sulfate, renal cortical homogenates from treated rats showed a 45% reduction in the activity of the basolateral enzyme marker, Na + ,K + -ATPase, while enzymes associated with the brush border membrane and other cellular organelles were not significantly altered. Tissue slice respiration, transport of p -aminohippuric acid (PAH), and N 1 -methylnicotinamide (NMN) and ionic content (Na, K, Ca) were unaffected by treatment. Cortical slices from gentamicin-treated rats showed a decreased capacity to extrude Na and regain K with respect to controls after cooling (0°C) and subsequent rewarning (37°C). Although light microscopic analyses revealed no significant changes in renal cortex 1.5 hr following injections of 50 to 350 mg/kg gentamicin, electron microscopy detected the presence of increased numbers of cytosegresomes at all doses. No other histopathological changes were evident. These results indicate that gentamicin affects the basolateral membrane of the proximal tubule and that inhibition of Na + ,K + -ATPase may be related to the pathogenesis.