Toxicological evaluation of aqueous leaf extract of Terminalia catappa linn (combretaceae) in pregnant rats

Abstract

Introduction: Terminalia catappa (T. catappa) leaves are used in the treatment of hypertension, diabetes, cough, jaundice, indigestion etc, while the bark is used to treat diarrhea, dysentery, abscesses etc. Due to the acceptance and increased use of medicinal plants in pregnancy, there is a need to evaluate their toxicological profiles in pregnancy for safe use. This study aims to evaluate the toxicological effects of aqueous leaf extract of T. catappa in pregnant rats.

Methods: acute toxicity study was carried out using Organization of Economic Corporation Development (OECD) 423 guidelines. Seventy-five rats (50 females and 25 males) were used at the age of 2 weeks just after weaning. The male rats were separated from the female rats in different cages and allowed to mature for 10 weeks. Then the rats were allowed to mate. After mating, 20 female rats with viable spermatozoa counts were selected and divided into 4 groups of 5 rats each (n=5). The control group received distilled water while the treatment groups II, III, and IV were administered with aqueous leaf extract of T. catappa orally at graded doses of 100, 200, and 400 mg/kg respectively for 21 consecutive days. The daily food and water intake, and weight were recorded. On the 22^th day, the rats were anesthetized by chloroform inhalation, and blood samples were collected for haematological and biochemical analysis. The maternal livers, kidneys, and hearts were collected and weighed, and histological studies were carried out. The fetuses were removed and examined. An isolated tissue experiment was carried out on the myometrium of the pregnant rat uterus. The isometric reading of the uterine contractions was recorded.

Results: the oral LD₅₀ was found to be ≤2000-5000 mg/kg. There was a significant (p<0.05) increase in the mean food intake at the 100, 200, and 400 mg/kg doses of the extract used on the 14^th and 21^st days when compared to the 7^th day. The renal function test showed a significant (p<0.05) increase for chloride. The liver function test revealed that the extract at 100 mg/kg dose, significantly (p<0.05) increased only Alkaline Phosphatase (ALP) liver enzyme, while at 200 mg/kg dose, only AST liver enzyme was significantly (p<0.05) increased, while at 400 mg/kg dose, ALT, AST, ALP, and albumin increased significantly (p<0.05) when compared to the control group. There was a significant (p<0.05) decrease in the relative organ weight of the liver at 400 mg/kg dose of the extract. The liver histology showed moderate hepatic vacuolation and necrosis, while the histology of the kidney showed slight tubular necrosis.

Conclusion: this study has shown that the aqueous leaf extract of T. catappa is relatively not safe in the pregnant rats. Although it is non-toxic to the fetus, it exhibited tocolytic effect by inhibiting uterine contractions, thus it should be used with caution during pregnancy, especially in the third trimester or during labor.