title: Reparation of Isoniazid and Rifampicin Combinatorial Therapy-Induced Hepatotoxic Effects by Bacopa monnieri.
abstract: Drug-induced liver injury is a major challenge in treating tuberculosis with isoniazid (INH) and rifampicin (RIF). This study was aimed at evaluating the protective effects of Bacopamonnieri (Brahmi) against INH and RIF-induced hepatotoxicity in a rat model and also to study the patterns of interaction between pregnane X receptor (PXR) and chosen active compounds of B. monnieri. Hepatotoxicity was induced in the experimental animals by the oral administration of INH and RIF (50 mg/kg b.w. each/day) for 28 days. The effects of co-administration of B. monnieri (500 mg/kg b.w./day) in INH- and RIF-induced rats were studied by the estimation of biochemical analyses. The standard hepatoprotective drug silymarin (25 mg/kg b.w./day) was used for the purpose of comparison. In silico docking experiments were carried out using the PatchDock server and the results were analysed on the PyMol molecular viewer. There was significant reduction in the antioxidant status of INH and RIF-induced rats. Also, there was significant elevation in the levels of serum liver function markers in the INH- and RIF-induced rats. B. monnieri was able to normalise the tested parameters. In silico studies reveal significant interaction between PXR and bacopaside I. B. monnieri exerts significant protective effects against INH and RIF-induced hepatotoxicity in rats.
authors.affiliation: School of Biosciences and Technology, VIT University, Tamilnadu, India.
authors.forename: Sabina
authors.initials: S
authors.lastname: Evan Prince
authors.forename: Lavinya B
authors.initials: LB
authors.lastname: Udhaya
authors.forename: Priyadharshini S
authors.initials: PS
authors.lastname: Sunitha
authors.forename: Geetha
authors.initials: G
authors.lastname: Arumugam
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000995:Antitubercular Agents / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D034681:Bacopa; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D007538:Isoniazid / Q000009:adverse effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000627:therapeutic use*; D020011:Protective Agents / Q000627:therapeutic use*; D017208:Rats, Wistar; D012293:Rifampin / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D010936:Plant Extracts; D020011:Protective Agents; D016753:Interleukin-10; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D007538:Isoniazid; D012293:Rifampin