INFLUENCE OF HYDRATION STATES ON THE ACUTE NEPHROTOXIC EFFECT OF GENTAMICIN IN THE RAT

The influence of acute water loading and water deprivation on gentamicin-induced nephrotoxicity was examined in rats by administering the drug (50 mg kg-1) into a group of hydrated rats and another 24 h-dehydrated group. Renal damage was assessed by measuring urinary enzymes, protein, urine flow rate and cell excretion in urine. Water loading alone caused significant alterations (2-5-fold) of the parameters under observation while these parameters were either lower or of comparable values to the untreated controls in water-deprived rats. Gentamicin administration further resulted in the elevation of all parameters in water-loaded rats. However, elevated alkaline phosphatase (P < 0.01), similar excretion of muramidase and decreased excretion of N-acetyl-beta-D-glucosaminidase compared to the controls was observed in water-deprived rats given gentamicin. Cells excreted in the urine were mainly renal tubular and squamous epithelial types in the control and all treated rats. These cells contain between 2 and 10% of the total enzyme activity in the urine of untreated-control rats. Increases in the percentage of these enzymes were observed as follows: in water-loaded (12-24%); water-deprived (4-26%); gentamicin alone (16-27%); water-loaded rats given gentamicin (11-30%); and water-deprived rats receiving gentamicin (8-15%). These observations demonstrate that the toxicity of gentamicin could be aggravated by both water loading and water deprivation. Water load alone is also associated with physiopathological changes in the kidney cells.