IN-SILICO STUDY OF TOXICITY MECHANISMS FOR METABOLITES OF PHYTO-COMPOUNDS FROM MUSA SP. COMPARED TO SYNTHETIC MEDICINE RANITIDINE

An in-silico attempt to predict rat oral acute toxicity, hepatotoxicity, immunotoxicity, genetic toxicity endpoints, nuclear receptor (NR) signaling, and stress response (SR) pathways of metabolites of synthetic medicine Ranitidine and flavonoids of Musa sp. The metabolites of common flavonoids and synthetic medicine were taken from literature, and the prediction was done by using ProTox-II webserver. The predictive results for the toxicity of these metabolites, N-nitrosodimethylamine obtained the lower LD₅₀ value (26 mg/kg) as highest toxicity of class II, i.e., prescribed as fatal after swallowing ranged between >5 and ≤50, and rest compounds were class IV and V i.e., harmful or may be harmful if swallowing ranged between >300 and ≤2000 and >2000 and ≤5000. None of these were showed hepatotoxic as well as not cytotoxic and mutagenic active, but few were immunotoxic, and all metabolites of synthetic origin and two phytometabolites viz. quercetin-3-glucuronide and 5-O-methylmyricetin were obtained carcinogenic active. In the case of NR signaling pathways and SR pathways, three compounds were active on different parameters. In conclusion, this in-silico study indicated that the metabolite (N-nitrosodimethylamine) of synthetic medicine, namely ranitidine showed highly toxic as well as carcinogenic while metabolites as Quercetin-3-glucuronide and 5-O-Methylmyricetin also showed carcinogenic, which may cause at a higher dose and chronic exposure. The present results are suitable for further experimental research on toxicity mechanisms with these metabolites with a narrow range. This predictive study is suggested for future experimental assays to validate the present results of these metabolites.