TOXICITY STUDY OF THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR RENTIAPRIL IN RATS

A three-months toxicity study of an angiotensin converting enzyme (ACE ) inhibitor, rentiapril (CAS 80830-42-8), was performed in Sprague-Daw ley rats by oral administration. The dose levels 0, 30, 125, 500 and 1 000 mg/kg were tested in both sexes, in which each experimental group comprised 10 rats. Another ACE inhibitor, captopril, was used as a ref erence compound. Rentiapril at the highest dose of 1000 mg/kg caused l ow food consumption and death of some animals with signs of bloody fec es and anemia. In males and females receiving 500 and 1000 mg/kg, ther e were low body weight gain, increases in water intake, urine volume a nd serum BUN level, and decreases in levels of various erythrocytic pa rameters in both sexes. Histopathologically, renal changes in the 500 and 1000 mg/kg groups consisted of porximal tubular degeneration, juxt aglomerular cell hyperplasia and interstitial cell infiltration. Simil ar, but mild, changes in proximal tubules were present in the female 1 25 mg/kg group. Dead animals from the highest dose groups further show ed gastrointestinal hemorrhagic erosion and/or ulcer, decreased bone m arrow erythropoiesis and hepatocytic vaculor degeneration. There was n ot pathological alteration in rats from other rentiapril-treated group s, as well as in controls. These results indicate that no-effect dose of retiapril in rats by three months oral administration is 30 mg/kg i n female and 125 mg/kg in male, and suggest that, like other ACE-inhib itors, this compound also has a toxic potential to affect renal tissue s.