Effects of a prostaglandin E₁ analogue, misoprostol, on gentamicin-induced nephrotoxicosis in dogs

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Virginia Tech

Autoregulation of renal blood flow is partly mediated by antagonistic vasodilating and vasoconstricting effects of products of the arachidonic acid cascade. Vasodilatory prostaglandins have been evaluated in experimental models of acute renal failure and clinical human medicine, with variable results. This study assessed potential protective effects of an oral prostaglandin E₁ analogue, misoprostol, in gentamicin-induced nephrotoxicosis in dogs.

Twelve dogs were initially assessed to be clinically healthy and to have normal renal function. Each received gentamicin (10 mg/kg intravenously, every 8 hours) for 8 days. Six dogs received oral placebo and 6 received misoprostol (3 µg/kg by mouth, every 8 hours) for the duration of study. Serum biochemical profiles, urinalyses, and exogenous creatinine clearances were monitored every 2 to 3 days.

Three dogs receiving misoprostol were withdrawn early because of severity of clinical signs. Changes in serum urea nitrogen, creatinine, potassium, chloride, total protein, and urine protein-to-creatinine ratio appeared more severe in dogs receiving misoprostol, but were not significantly different between groups over time. Exogenous creatinine clearances were significantly decreased in dogs receiving misoprostol. Histopathological changes included patchy necrosis of renal proximal and were not significantly different between groups.

Administration of misoprostol appeared to adversely affect glomerular filtration rates in this model of acute nephrotoxicosis in dogs. In previous studies, supplementing vasodilatory prostaglandins in experimental acute renal failure had beneficial effects or there were no changes in renal function. Additional study is needed to assess effects of manipulating vasoactive products of the arachidonic acid cascade in renal failure.

nephrotoxicosis, misoprostol, prostaglandins, gentamicin, dogs