Toxicity, mutagenicity and trace metal constituent of Termitomyces schimperi (Pat.) R. Heim (Lyophyllaceae) and kaolin, a recipe used traditionally in cancer management in Cote d'Ivoire.

ETHNOPHARMACOLOGICAL RELEVANCE: Some local communities in Cote d'Ivoire use the mushroom Termitomyces schimperi combined with kaolin (TSK) to manage various cancers in patients. However, there is a paucity of data on toxicity, mutagenicity and trace metal constituent of TSK. AIM OF THE STUDY: We sought to investigate the acute and sub-chronic toxicities, mutagenic potential, and trace metal constituents of TSK. MATERIALS AND METHODS: To assess acute toxicity, single doses (1000, 3000 and 5000 mg/kg) of aqueous extract of TSK were administrated per os to Sprague Dawley (SD) rats on Day 1. The rats were then monitored for 13 consecutive days. Sub-chronic toxicity was evaluated by daily administration of 200 and 500 mg/kg of the extract per os for 90 consecutive days. SD rats used as control received distilled water. Signs of toxicity, changes in body weight and mortality were monitored. After the aforementioned monitoring processes, rats were sacrificed and blood collected for full blood count and biochemistry analysis. Animal organs were also collected for histopathological examination. The mutagenic potential of the aqueous extract of TSK (10000 µg/mL) on TA98 Salmonella typhimurium was estimated. Additionally, energy-dispersive X-ray fluorescence (ED-XRF) method was employed to determine trace metal constituents of TSK. RESULTS: Single-dose administration of 5000 mg/kg of TSK did not cause any death in the SD rats; thus, LD50 was above 5000 mg/kg. Administration of 1000 and 3000 mg/kg of the aqueous extract of TSK did not cause any significant change in behaviour and body weight of SD rats during the 14-day monitoring period. However, the mean corpuscular volume and the mean corpuscular haemoglobin concentration increased significantly (p < 0.01) among rats administered 1000 and 3000 mg/kg of TSK. There was a significant increase (p < 0.0001) in alanine transaminase levels in rats administered 1000 and 3000 mg/kg of TSK extract compared with control. Conversely, there was a significant decrease (p=0.0122) in serum creatine level among rats administered 1000 and 3000 mg/kg of TSK extract compared with control. After 14 days, there were minimal changes with isolated organs of TSK-treated and control rats. Furthermore, 90-day treatment with extract of TSK caused no significant change in parameters assessed. TSK induced frameshift gene mutation in S. typhimurium before (p < 0.05) and after metabolic activation (p < 0.001). Elemental analysis of TSK revealed the presence of toxic (aluminium) or potentially toxic (silver, rabidium, titanium and zirconium) elements. CONCLUSIONS: The aqueous extract of TSK showed no toxicity (acute and sub-chronic) at doses tested. These findings are consistent with the absence of heavy metals (i.e., cadmium) and potentially toxic elements (i.e., uranium) in TSK samples analysed. TSK showed some level of mutagenic potential. Further mutagenic and chronic toxicity studies on TSK are required.

A dietary strategy for the management of artemether-lumefantrine-induced cardiovascular and renal toxicity.

BACKGROUND: Unsweetened natural cocoa has antimalarial properties. Unsweetened natural cocoa powder (UNCP), obtained as a result of the removal of cocoa butter from a cocoa bean protects against malaria episodes. Cocoa powder, which is prepared after removal of the cocoa butter, contains about 1.9 % theobromine and 0.21 % caffeine. Concomitant consumption of cocoa and artemether/lumefantrine (A/L) is a common practice in Ghana, West Africa. This study seeks to determine the elemental composition of UNCP and its protective effect on the heart and kidney against (A/L) administration. METHODS: Energy dispersive x-ray fluorescence spectroscopy was used to detect the quality and quantity of the elemental composition in UNCP. Thereafter, 30 nonmalarious male guinea pigs were divided into five groups of six animals each. One group was administered with 75 mg/kg body weight A/L only and another group distilled water (control group). The rest received 300 mg/kg, 900 mg/kg and 1500 mg/kg body weight UNCP for 14 days orally and A/L for the last 3 days (ie day 11 to day 14). Biochemical and histopathological examinations were carried out after euthanisation of the animals. RESULTS: A total of thirty-eight (38) micro and macro elements were detected with the ED-XRF. Macro elements like sodium (Na), magnesium (Mg), aluminium (Al), phosphorus (P), chlorine (Cl), potassium (K), calcium (Ca), manganese (Mn) and iron (Fe) and micro elements like chromium (Cr), copper (Cu), zinc (Zn), arsenic (As), and lead (Pb) were identified and evaluated. Biochemical analysis revealed increases in HDL levels (p>0.05) while there were decreases in LDL levels (p>0.05), creatine kinase and AST levels (P<0.05) in animals that received UNCP compared to A/L only administered group. Urea levels reduced significantly by 53 % (p<0.05) in group that received 1500 mg/kg UNCP. Histopathological examinations of the heart and kidney buttressed the protective effects of cocoa administration. CONCLUSION: The percentage of recommended daily allowance of UNCP for chromium is 3750 % for men and 5250 % for women while % RDA for copper corresponds to 103.6 % in both sexes. UNCP proved to possess cardioprotective and renoprotective potential during artemether-lumefantrine administration.