NovaSil clay intervention in Ghanaians at high risk for aflatoxicosis. I. Study design and clinical outcomes.

A 3-month double-blind and placebo-controlled, phase IIa clinical trial was conducted in Ghana to investigate the safety, tolerance and aflatoxin-sorption efficacy of dietary NovaSil (NS). Volunteers (507 subjects) were clinically screened to evaluate their general health, pregnancy status and blood AFB(1)-albumin adduct levels. Of these subjects, 177 were randomly assigned to three groups: high-dose (HD), low-dose (LD) and placebo-control (PL) groups receiving 3.0, 1.5 and 0 g NS day(-1) in capsules. Trained study-monitors supervised NS capsule administration to participants and recorded side-effects daily. Physical examinations were performed monthly. Blood and urine samples were collected for laboratory analysis. Approximately 92% of the participants (162 of 177) completed the study and compliance rate was over 97%. Overall, 99.5% of person x time reported no side-effects throughout the study. Mild to moderate health events ( approximately 0.5% of person x time) were recorded in some participants. Symptoms included nausea, diarrhea, heartburn and dizziness. These side-effects were statistically similar among all three groups. No significant differences were shown in hematology, liver and kidney function or electrolytes in the three groups. These findings demonstrate that NS clay is apparently safe and practical for the protection of humans against aflatoxins in populations at high risk for aflatoxicosis.

Subchronic toxicity studies of the antidiabetic herbal preparation ADD-199 in the rat: absence of organ toxicity and modulation of cytochrome P450.

The subchronic toxicity of the aqueous antidiabetic herbal extract ADD-199, prepared from Maytenus senegalensis, Annona senegalensis, Kigelia africana and Lanneawelwitschii, and administered at a daily dose of 100 or 500 mg/kg body weight over 30 days, was investigated in male Wistar albino rats. Certain haematological, urine and plasma biochemical parameters, and modulation of some hepatic cytochrome P450 (CYP) isozymes were measured as indices of organ specific toxicity or potential for drug interactions. ADD-199 did not affect plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and albumin or creatinine kinase (CK) levels. It also did not affect plasma creatinine and urea levels. Furthermore, ADD-199 neither affected PCV nor blood Hb, RBC, reticulocytes, platelets, lymphocytes and granulocyte levels. It, however, caused significant dose-dependent reductions in WBC counts at day 15 with varying degrees of recovery by day 30. It also reduced the rate of body weight increases after week 3. However, no changes were observed in organ weights at termination. ADD-199 did not significantly affect zoxazolamine-induced paralysis and pentobarbital-induced sleeping times as well as certain CYP isozyme activities in rats. These findings suggest that ADD-199 had no overt organ specific toxicity and did not demonstrate a potential for drug interactions via CYP-mediated metabolism in the rat on subchronic administration.

The antidiabetic activity of the herbal preparation ADD-199 in mice: a comparative study with two oral hypoglycaemic drugs.

The antidiabetic and antioxidant effects of the herbal preparation ADD-199 were investigated in STZ-induced diabetic C(3)H mice and results were compared with two allopathic hypoglycaemic drugs, glibenclamide and metformin. Plasma glucose, insulin and lipids as well as liver glycogen, lipids and lipid peroxidation were measured following treatment for 8 weeks. The results indicated that plasma insulin levels in normal controls at termination were about 76 micromol/L compared to trace levels in untreated diabetic mice. Glibenclamide and ADD-199 increased insulin levels in diabetic mice up to 70% of levels in untreated non-diabetic mice whilst metformin had no effect. Basal plasma glucose levels in diabetic controls (18.8 mM) were reduced to 14.0 mM by 100 mg/kg ADD-199 in <2 weeks compared to 4 and 6 weeks for glibenclamide and metformin, respectively. This hypoglycaemic effect of ADD-199 appeared to be associated with the alkaloidal content of the extract. Treatment with ADD-199 or the hypoglycaemic agents reversed the observed elevation in plasma lipids but increased hepatic glycogen, triacylglycerol and cholesterol levels. Treatment also increased glucose uptake by isolated diaphragms and attenuated hepatic lipid peroxidation. These antihyperglycaemic and antioxidant actions of ADD-199 at a dose of 100mg/kg/day are comparable to those of the maximum daily therapeutic doses of glibenclamide (0.25 mg/kg) and metformin (50 mg/kg). These could explain the basis for use of this plant extract to manage diabetes mellitus (DM).

Extract of Ocimum canum lowers blood glucose and facilitates insulin release by isolated pancreatic beta-islet cells.

Aqueous extract of Ocimum canum Sim, (Lamiaceae) is used by some Ghanaians to manage diabetes mellitus. In vivo modulation of levels of fasting blood glucose by 0. canum extract was evaluated in type-II diabetes mellitus using the C57BL/KsJ db/db genetically diabetic animal model, and its effects on glucose-stimulated insulin release in vitro were monitored using isolated rat pancreatic beta-islet cells. The results showed that fasting blood glucose levels and body weight decreased significantly (p < 0.05) in diabetic and non-diabetic C57BL/KsJ mice, which were administered aqueous extract of 0. canum. In vitro, the 0. canum extract significantly enhanced insulin release from isolated rat pancreatic beta-islet cells. Insulin release was found to be dependent on glucose concentration and increased with increasing O. canum concentration in the incubation medium up to an optimum extract concentration of 0.03 mg/ml. Release of the hormone decreased beyond this concentration of extract in the medium. Addition to the medium of Desmodium adscendens, a plant preparation used to manage inflammatory disorders, did not increase but rather inhibited insulin secretion by the pancreatic beta-islet cells. These results could explain the use of 0. canum in Ghanaian folk medicine to manage diabetes mellitus.

Acute and subchronic evaluation of Indigofera arrecta: absence of both toxicity and modulation of selected cytochrome P450 isozymes in ddY mice.

Indigofera arrecta, an anti diabetic plant was investigated in ddY mice to determine its acute and subchronic effects, and whether it modulated hepatic cytochrome P450 (CYP) isozymes and glutathione (GSH). No mortality was observed in the acute (up to 10 g I. arrecta/kg body wt, p.o.) and subchronic (2 g I. arrecta/kg body wt, p.o. daily for 30 days) studies. The extract did not alter haematological indices, serum and tissue lipids and glutathione but lowered serum bile acids. The latter phenomenon is under further investigation. Neither the duration of pentobarbital (PB) and zoxazolamine (ZA) effects in vivo, nor CYP-dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-depentylase (PROD) and p-nitrophenol hydroxylase (PNPH) activities in vitro were altered by I. arrecta. The extract was thus devoid of overt acute and subchronic toxic effects, and did not affect CYPs and GSH whose modulation may cause interactions of components in a multiple drug therapy.

Biliary excretion in persons with low blood glutathione levels.

A study to investigate the association between blood glutathione (GSH) levels and biliary excretory status was conducted in apparently healthy Ghanaian subjects without frank biliary disease and anaemia. The results showed that, in adults (mean age: 38.5 years) and children (mean age: 13.0 years), plasma conjugated bilirubin is inversely correlated with blood GS (respective site r = -0.524, p < 0.011 and -0.395, p < 0.005). Persons with elevated plasma conjugated bilirubin compared to controls (mean: 6.0 versus 2.5 umol/L, p < 0.001) also exhibited low blood GSH values (3.5 versus 4.2 umol/gHb, p < 0.029). Malaria parasites with counts up to 2,453 parasites/ul blood had no effect on the obtained data. The results suggest that low blood GSH levels may be relevant to delays in biliary excretion of conjugated toxins from the liver, as exemplified by the rise in conjugated bilirubin levels in the plasma, and predispose liver cells to increased oxidant state and damage.

Lead exposure in urban and rural school children in Ghana.

Human exposure to lead in non industrial urban areas is commonly ascribed to vehicular combustion of leaded gasoline. This belief is based on results of studies in societies with high vehicular density which show emission of lead fumes into the air by automobiles that use gasoline with high lead content. To assess this view, blood lead levels were evaluated in 11 to 15-year old school children in urban and rural communities of the Greater Accra Region, Ghana. Blood lead levels was significantly higher in all the urban children studied (mean +/-SD: 8.3+/- 12.7g/dl) than in their rural counterparts (4.0+/-7.2g/dl) (P<0.002). The trend was the same when only those who tested positive for blood lead were considered (24.1+/- 9.2g/dl, urban compared with 14.6+/- 5.8g/dl, rural). The prevalence of lead exposure was, however, not significantly different between the two groups (34.3. percent, urban and 27.1 per cent, rural). The presence of anaemia and/or increased urine total protein levels was unrelated to the blood lead levels in the children form both communities. Although a set goal to achieve lead free gasoline is desirable, the closeness of the prevalence rate of lead exposure obtained in the study indicate that factors other than leaded gasoline may be important determinant in exposure to lead in the Ghanaian community.