Abstrato

Toxic effects of antituberculosis drugs (isoniazid and rifampicin) on feto-placental unit of wistar rats: a morphological, histological and biochemical study.

Vitalis Chukwuma Ezeuko, Jacob Ehiagwina Ataman, Dorothea Baxter-Grillo

The aim of this study was to investigate the effects of chronic administration of therapeutic doses of isoniazid and rifampicin individually and in combination to the foetal weight, placental weight, foetal/placental weight ratio, placental oxidative stress and placental histomorphology of Wistar rats. A total of twenty-eight adult female Wistar rats weighing between 160 g and 170 g, aged between 90 days and 110 days were used for this study. They were divided into four groups (A, B, C and D) of seven rats each. Group A served as the control group administered with only sterile water. Group B animals were administered 5 mg/kg body weight of isoniazid only. Group C animals were administered 10 mg/kg body weight of rifampicin only. Group D animals were administered 5 mg/kg body weight of isoniazid and 10 mg/kg body weight of rifampicin. Day 20 foetal body weight significantly reduced in the isoniazid-treated and rifampicin-treated groups. Day 20 placental weight was significantly increased while day 20 foetal:placental weight ratio was significantly reduced in all the experimental groups. Placental superoxide dismutase, catalase and glutathione peroxidase activities were significantly reduced in all the experimental groups. Histological studies of the placenta showed varying degrees of alterations including degeneration of trophoblastic giant cells, haemorrhage in the junctional zone, dilation and congestion of maternal sinusoids and mild dilation and congestion of foetal capillaries. In conclusion, administration of isoniazid and rifampicin singly and in combination at therapeutic doses induced intrauterine growth restriction with compensatory placental hypertrophy and associated oxidative stress and alterations in the histomorphology of the placental tissues.