title: Amelioration of anti-tuberculosis drug induced oxidative stress in kidneys by Spirulina fusiformis in a rat model.
abstract: Nephrotoxicity is a rare complication caused by anti-tuberculosis therapy-induced oxidative stress. The Cyanobacterium Spirulina fusiformis Voronikhin belonging to Oscillatoriaceae family is used traditionally as a source of antioxidants against oxidative stress. We aimed to investigate the efficacy of S. fusiformis in modifying isoniazid (INH) and rifampicin (RIF)-induced changes in Wistar rat kidneys. Animals were divided into six groups: normal control rats; toxic control (INH & RIF-50 mg/kg b.w./d each; p.o.); INH & RIF + S. fusiformis (400 mg/kg b.w./d); INH & RIF + S. fusiformis (800 mg/kg b.w./d); S. fusiformis (800 mg/kg b.w./d) alone-treated rats; INH & RIF + silymarin (25 mg/kg b.w./d). Study duration was 28 d after which blood and kidneys were analyzed. We also studied the binding and interactions of the transcription factors Liver X Receptor (LXR) and Farnesoid X Receptor (FXR) with INH, RIF, and representative active compounds of S. fusiformis by in silico methods. INH & RIF treatment caused significant (p< 0.05) decrease in antioxidant levels and significant (p< 0.05) increase in the levels of creatinine, urea, and uric acid showing impaired kidney function. Spirulina fusiformis ameliorated these effects in a dose dependent manner. Histological examination of kidneys supported these findings. Results of the in silico analyses showed that selected active components of S. fusiformis interact with LXR and FXR and could be a possible mechanism of action. S. fusiformis rendered protection against anti-tuberculosis drugs-induced oxidative stress in kidney tissues of rats.
authors.affiliation: a Department of Bio-Medical Sciences, School of Bio Sciences and Technology, VIT University , Vellore , Tamil Nadu , India.
authors.forename: Sherry Joseph
authors.initials: SJ
authors.lastname: Martin
authors.affiliation: a Department of Bio-Medical Sciences, School of Bio Sciences and Technology, VIT University , Vellore , Tamil Nadu , India.
authors.forename: Evan Prince
authors.initials: EP
authors.lastname: Sabina
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism*; D000995:Antitubercular Agents / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012293:Rifampin / Q000009:adverse effects; D012838:Silymarin / Q000008:administration & dosage; D053545:Spirulina / Q000737:chemistry*; D014508:Urea / Q000097:blood; D014527:Uric Acid / Q000097:blood; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000975:Antioxidants; D000995:Antitubercular Agents; D003404:Creatinine; D007538:Isoniazid; D020011:Protective Agents; D018160:Receptors, Cytoplasmic and Nuclear; D012293:Rifampin; D012838:Silymarin; D014508:Urea; D014527:Uric Acid; D000099150:Receptor, Farnesoid X-Activated
keywords: Farnesoid-X-receptor; isoniazid; liver-X-receptor; nephrotoxicity; rifampicin; tuberculosis