Prenatal zestoretic exposure ameliorates developmental landmarks in rat offspring

Abstract

Zestoretic, a combination of lisinopril and hydrochlorothiozide used as anti-hypertension drug prescribed even during pregnancy. Role of zestoretic on the developmental landmars of young ones exposed prenatally are yet to be established. Hence, the present investigation initiated to test in Wistar rats. Three groups of inseminated female rats were oral gavaged with zestoretic (lisinopril varied concentrations + hydrochlorothiozide 12.5mg) 25, 50 and 100 mg/Kg body weight (BW) on gestation days 7, 9, 11 and 13, whereas control group with double distilled water. Clinical toxicity found in few dams from 50 and 100 mg/Kg BW received rat shown aggressive behavior during experimentation. The developmental landmarks, such as pinna attachment, ear opening, fur development, eye opening, upper and lower incisor eruption, crown rump length, vaginal opening and testes descend were measured periodically on their postnatal days in all the young ones. The number of live pups in zestoretic 50, 100 mg/Kg BW administered females are significantly less (P<0.001) from control. Comparatively among the groups, sex ratio of male and female offspring is not changed. The BW of young ones on postnatal day (PND) 1, 7, 14 and 21 are significantly (P<0.001) reduced in 100 mg zestoretic exposed ones compared to other groups, but weight loss is dose dependent in experimental groups. Decreased survival index of pups exposed to zestoretic 50; 100 mg/Kg BW was reported.Recorded, delay in pubertal onset in females (vaginal opening) and testicular descent in males of experimental groups. Crown rump length in experimental offspring is significantly (P<0.05) decreased from controls in a dose dependent manner on PND 1, 7, 14 and 21. No change has been recorded with anogenital distance, pinna detachment, eye and ear opening, fur development, lower and upper incisor eruption, experimental offspring when compared to controls. The present study establishing the interference of prenatal zestoretic exposure on some of the developmental landmarks in the offspring of rats.