Calcium supplementation and thyroid hormone protect against gentamicin‐induced inhibition of proximal tubular Na+, K+‐ATPase activity and other renal functional changes

Publisher Website
Google Scholar
Abstract
Gentamicin can cause proximal tubule necrosis. We have shown that inhibition of PT Na+, K+‐ATPase activity is rapidly induced by gentamicin. We have now investigated whether manipulations known to attenuate the negative effects of gentamicin on renal excretory capacity, i.e. high calcium intake and L‐thyroxine treatment, will also attenuate gentamicin‐induced inhibition of Na+, K+‐ATPase activity and ameliorated signs of proximal tubule damage. Rats were gentamicin‐ or vehicle‐treated for 7 days. Sub‐groups were given 4% calcium (Ca) supplements or L‐thyroxine 20μg 100 g‐1body weight daily. Gentamicin significantly reduced the glomerular filtration rate and increased the urinary excretion of the proximal tubule lysosomal enzyme,N‐acetyl‐β‐d‐glucosaminidase. Gentamicin significantly reduced proximal tubule Na+, K+‐ATPase activity, measured in single permeabilized proximal tubule segments. Sodium excretion was inversely correlated to proximal tubule Na+, K+‐ATPase activity. Both calcium and L‐thyroxine alleviated all gentamicin‐induced side‐effects on renal function as well as on proximal tubule Na+, K+‐ATPase activity. Calcium and L‐thyroxine had no significant effect on renal function. L‐thyroxine, but not calcium, increased proximal tubule Na+, K+‐ATPase activity in control rats. Renal cortical tissue gentamicin concentration was not influenced by calcium but was significantly lowered by L‐thyroxine.Two procedures which, via different mechanisms, afford protection from gentamicin‐induced changes in renal function also give protection from gentamicin‐induced inhibition of Na+, K+‐ATPase activity. This suggests that loss of integrity of the Na+, K+‐ATPase enzyme contributes to gentamicin‐induced nephrotoxicity.