Differential effects of carbamazepine and levetiracetam monotherapy on reproductive endocrine function in Nigerian women with epilepsy.

Objective: This study is aimed at comparing differential effect of Levetiracetam (LTC) monotherapy and Carbamazepine (CZP) monotherapy in W omen with epilepsy (WWE) on gonadal hormone. Methods: 87 WWE were recruited comprising randomly of 46 and 41 on CZP and LTC group respectively with diagnosis and classification based on International League Against Epilepsy (ILAE). Reproductive hormones (Luteinizing Hormone (LH), Follicle stimulating hormone, progesterone, estradiol and testosterone) were assayed. National Hospital Seizure Severity Scale (NHSS) and Zung self-reporting depression scale (ZSRDS) were used to assess the seizure severity and the mood respectively. Data was analyzed using Statistical Package for Social Sciences (SPSS) version 20. The Chi-square test was used to compare categorical variables while Student's t-test or its non-parametric equivalent where appropriate were used to compare continuous variables. Results: Clinical characteristics were comparable in both groups except for ZSRDS (p = 0.048), NHSS (p = 0.012) and hip circumference (p = 0.037). The CZP group had a higher ASEX score and proportion of WWE with clinically significant sexual dysfunction (p < 0.001). WWE on LTC had similar hormonal profiles with those on CZP except for a higher median serum testosterone level (p = 0.004), and lower median serum LH (p = 0.006). Age was negatively associated with serum testosterone level for the 25th, 50th, and 75th quartile. However, the differential effect for AED type was only significant for the 25th quartile; with higher values in LTC. Conclusion: The therapeutics implication of lower LH and testosterone levels in the LTC group compared to CZP group need to be explored.

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

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 22th 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 14th and 21st days when compared to the 7th 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.

Toxicological evaluation of hydroethanol leaf extract of Pupalia lappacea (Linn.) Juss. (Amaranthaceae) in rodents.

OBJECTIVES: Several studies have established the ethnobotanical benefits of Pupalia lappacea (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of P. lappacea in rodents was carried out in this study. METHODS: Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods. RESULTS: The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible. CONCLUSIONS: The findings showed that P. lappacea is relatively safe at lower doses but cautions should be taken at higher dose.

Toxicological evaluation of hydroethanol leaf extract of Pupalia lappacea (Linn.) Juss. (Amaranthaceae) in rodents.

OBJECTIVES: Several studies have established the ethnobotanical benefits of Pupalia lappacea (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of P. lappacea in rodents was carried out in this study. METHODS: Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods. RESULTS: The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible. CONCLUSIONS: The findings showed that P. lappacea is relatively safe at lower doses but cautions should be taken at higher dose.