Abstract
Background: The efforts are done to assess the properties of drug excipient to act as agent to bring about reduced teratogenic effects of drugs that can be used for treatment of metabolic disorders. Objective: To evaluate anti-teratogenic effects of β cyclodextrin against tolbutamide induced teratogenecity in Wistar rats. Methods: 3 groups comprising 10 mated female Wistar rats were exposed with β cyclodextrin (750 mg/kg), tolbutamide (400 mg/kg), β cyclodextrin + tolbutamide (750 + 400 mg/kg) during gestation day 6 to 18 and concurrent vehicle control group dosed with 0.5% CMC. β cyclodextrin was given 1 hr prior to tolbutamide treatment. The females were sacrificed on presumed gestation day 20 to assess the uterine parameters and fetal observations including visceral and skeletal examination. Results: No deaths and clinical signs occurred in this study. No test substance related changes in body weight, food consumption and gross pathological findings noticed. The uterine parameters such as Mild increase in no. of early resorptions was noticed in females treated with tolbutamide at 400 mg/kg B. wt and dam receiving combination of β cyclodextrin and tolbutamide. The post implantation loss was slightly higher in groups treated with in combination of β cyclodextrin and tolbutamide (750 + 500 mg/kg) . In the present study, the mean body weights of fetuses (male and female) were significantly decreased in tolbutamide treated group. Fetus of dam treated with tolbutamide showed decrease in CRL than the control group. Conclusion: The result of above study can be used to prevent teratogenic action of various useful drugs used in human and veterinary medicine. This experiment can be used as initial steps to study anti-teratogenic effect of various natural, artificial compound and their derivates to maintain therapeutic value of various popular drugs used in human and veterinary medicine (Table 1).
Highlights
Tolbutamide (1-butyl3-p-tolylsulfonylurea) is a first-generation sulfonylurea oral hypoglycemic agent used to treat non insulindependent diabetes mellitus (NIDDM) [1]
The result of above study can be used to prevent teratogenic action of various useful drugs used in human and veterinary medicine. This experiment can be used as initial steps to study anti-teratogenic effect of various natural, artificial compound and their derivates to maintain therapeutic value of various popular drugs used in human and veterinary medicine (Table 1)
The present investigation was undertaken to determine the antiteratogenic action of β cyclodextrin against tolbutamide induced teratogenecity in Wistar rat
Summary
Tolbutamide (1-butyl3-p-tolylsulfonylurea) is a first-generation sulfonylurea oral hypoglycemic agent used to treat non insulindependent diabetes mellitus (NIDDM) [1]. Gestational diabetes usually develops after the 24thweek of pregnancy because of the counter-insulin effects of placental hormones such as human placental lactogen, oestrogen and cortisol. It can be well controlled in most cases by diet alone. The embryonic pancreas is not yet present at this stage, so any direct effect of tolbutamide on the embryo must be due to extra-pancreatic targets [4,5] which may, serve as an important target for the dysmorphogenic action of tolbutamide. It is not possible to discriminate between potential teratogenic effects of TOLB and malformations produced by either drug-induced hypoglycemia or the diabetic state itself. The efforts are done to assess the properties of drug excipient to act as agent to bring about reduced teratogenic effects of drugs that can be used for treatment of metabolic disorders
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