Effects of chronic stavudine exposure on liver, pancreas and kidneys of pregnant rats and their fetuses: Morphological and biochemical aspects

Objective: To study the morphological and biochemical effects on liver, pancreas and kidney of pregnant rats and their fetuses subjected to stavudine treatment. Methods: Forty animals were distributed in four groups E1, E2, E3, and C (control) and received by gavage once a day 1, 3 or 9 mg/kg of stavudine in 2 mL distilled water, from days 1 to 20 of pregnancy. After this period, the animals were sacrificed; blood samples were collected for further determinations of AST, ALT, creatinine, urea, glucose and amylase. Samples of liver, kidneys and pancreas of every rat and of the corresponding fetuses were taken and examined under light microscopy. Results: The maternal livers of groups E1, E2 and E3 displayed progressive morphological alterations without corresponding changes in serum AST and ALT activity. Maternal kidney histology and function were similar in all groups. Maternal pancreas of groups E2 and E3 evidenced moderate and progressive signs of tissue damage without functional repercussion. All fetal livers, kidneys and pancreas presented normal morphology. Conclusions: High doses of stavudine produced signs of mild to moderate maternal hepatic and pancreatic toxicity at the morphological level. This was not followed by changes in biochemical parameters, most conceivably due to the functional reserve of these organs. (C) 2006 Elsevier Ireland Ltd. All rights reserved.