| In vivo | A three-month toxicity study of Rentiapril (CAS 80830-42-8), an angiotensin-converting enzyme (ACE) inhibitor, is conducted in Sprague-Dawley rats through oral administration. Dose levels of 0, 30, 125, 500, and 1000 mg/kg are tested in both sexes, with each experimental group consisting of 10 rats. Captopril, another ACE inhibitor, is used as a reference compound.At the highest dose of 1000 mg/kg, Rentiapril causes low food consumption and death in some animals, presenting signs of bloody feces and anemia. In males and females receiving 500 and 1000 mg/kg, there are low body weight gain, increases in water intake, urine volume, and serum BUN level, and decreases in various erythrocytic parameters. Kidney weight increases dose-dependently in both sexes. Histopathologically, renal changes in the 500 and 1000 mg/kg groups consist of proximal tubular degeneration, juxtaglomerular cell hyperplasia, and interstitial cell infiltration. Similar but milder changes in proximal tubules are present in the female 125 mg/kg group. Dead animals from the highest dose groups further show gastrointestinal hemorrhagic erosion and/or ulcer, decreased bone marrow erythropoiesis, and hepatocytic vacuolar degeneration. No pathological alterations are observed in rats from other Rentiapril-treated groups or in controls. These results indicate that the no-effect dose of Rentiapril in rats, following three months of oral administration, is 30 mg/kg in females and 125 mg/kg in males[1]. |
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