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

• Published in: Journal of ethnopharmacology 2005-02, Vol.97 (2), p.319-325
• Main Authors: Nyarko, A.K., Okine, L.K.N., Wedzi, R.K., Addo, P.A., Ofosuhene, M.
• Format: Article
• Language: English
• Subjects: ADD-199; Animals; Annona senegalensis; Antidiabetic; Biological and medical sciences; blood chemistry; Body Weight - drug effects; cytochrome P-450; Cytochrome P-450 Enzyme System - drug effects; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450; drug interactions; General pharmacology; herbal medicines; hypoglycemic agents; Hypoglycemic Agents - toxicity; Kigelia; Kigelia africana; Lannea; Lannea welwitschii; liver; Male; Maytenus; Maytenus senegalensis; Medical sciences; Microsomes, Liver - drug effects; Microsomes, Liver - enzymology; Microsomes, Liver - metabolism; Organ; Organ Size - drug effects; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; plant extracts; Plant Preparations - toxicity; Rat; Rats; Rats, Wistar; subchronic toxicity; Toxicity; urine
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2004.11.021

The subchronic toxicity of the aqueous antidiabetic herbal extract ADD-199, prepared from Maytenus senegalensis, Annona senegalensis, Kigelia africana and Lannea welwitschii, 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.