title: Attenuation of anti-tuberculosis therapy induced hepatotoxicity by Spirulina fusiformis, a candidate food supplement.
abstract: Therapy using Isoniazid (INH) and Rifampicin (RIF) leads to induction of hepatotoxicity in some individuals undergoing anti-tuberculosis treatment. In this study, we assessed the effect of Spirulina fusiformis on INH and RIF induced hepatotoxicity in rats compared with hepatoprotective drug Silymarin. Induction of hepatotoxicity was measured by changes in the liver marker enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase). The antioxidant status was also analyzed in liver tissue homogenate and plasma by measurement of superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, and lipid peroxidation levels. We also aimed to study the binding and interactions of the transcription factors Pregnane X Receptor (PXR) and Farnesoid X Receptor (FXR) with INH, RIF, and representative active compounds of Spirulina fusiformis by in silico methods. The administration of INH and RIF resulted in significant (p < 0.05) decrease in the antioxidant levels and total protein levels. There was also a significant (p < 0.05) increase in the levels of liver marker enzymes. Spirulina fusiformis was seen to protect the parameters from significant changes upon challenge with INH and RIF in a dose-dependent manner. This was corroborated by histological examination of the liver. The results of the in silico analyses further support the wet lab results.
authors.affiliation: School of Biosciences and Technology, VIT University , Vellore, Tamil Nadu , India.
authors.forename: Sherry Joseph
authors.initials: SJ
authors.lastname: Martin
authors.forename: Udhaya Lavinya
authors.initials: UL
authors.lastname: Baskaran
authors.forename: Mahima
authors.initials: M
authors.lastname: Vedi
authors.forename: Evan Prince
authors.initials: EP
authors.lastname: Sabina
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D007538:Isoniazid / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000097:blood / Q000378:metabolism; D000077297:Pregnane X Receptor; D019936:Probiotics / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D020011:Protective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism; D011987:Receptors, Steroid / Q000737:chemistry / Q000378:metabolism; D012293:Rifampin / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D012838:Silymarin / Q000627:therapeutic use; D053545:Spirulina; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000904:Antibiotics, Antitubercular; D007538:Isoniazid; D008024:Ligands; D010088:Oxidoreductases; D000077297:Pregnane X Receptor; D020011:Protective Agents; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D012293:Rifampin; D012838:Silymarin; D000099150:Receptor, Farnesoid X-Activated
keywords: Hepatoprotective; hepatotoxicity; isoniazid; rifampicin; spirulina; tuberculosis