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.
Subject(s)
Antibiotics, Antitubercular/adverse effects , Chemical and Drug Induced Liver Injury/prevention & control , Liver/drug effects , Models, Molecular , Probiotics/therapeutic use , Protective Agents/therapeutic use , Spirulina , Animals , Antibiotics, Antitubercular/chemistry , Antibiotics, Antitubercular/metabolism , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Drug Therapy, Combination/adverse effects , Female , Isoniazid/adverse effects , Isoniazid/antagonists & inhibitors , Isoniazid/chemistry , Isoniazid/metabolism , Ligands , Lipid Peroxidation , Liver/metabolism , Liver/pathology , Molecular Conformation , Molecular Docking Simulation , Organ Size/drug effects , Oxidoreductases/blood , Oxidoreductases/metabolism , Pregnane X Receptor , Probiotics/administration & dosage , Probiotics/chemistry , Protective Agents/administration & dosage , Protective Agents/chemistry , Rats, Wistar , Receptors, Cytoplasmic and Nuclear/chemistry , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Steroid/chemistry , Receptors, Steroid/metabolism , Rifampin/adverse effects , Rifampin/antagonists & inhibitors , Rifampin/chemistry , Rifampin/metabolism , Silymarin/therapeutic useABSTRACT
BACKGROUND: The present study was conducted to elucidate the protective role of Withania somnifera against bromobenzene induced nephrotoxicity and mitochondrial dysfunction in rats. METHODS: In this study, Wistar albino rats of either sex were divided into six groups consisting of six animals each. The first one was control, those in group II received bromobenzene (10 mmol/kg, intragastric intubation) once, but group III and IV animals received W. somnifera (250 and 500 mg/kg, orally), respectively for 8 days followed by bromobenzene once on the 8th day and silymarin (100 mg/kg, orally) was given for 8 days to group V animals and then bromobenzene on the last day. Group VI animals received only W. somnifera (500 mg/kg) for 8 days. RESULTS: The levels of renal lipid peroxidation, lysosomal enzymes and glycoprotein were increased significantly (p<0.05) in the bromobenzene alone treated rats and antioxidant status and mitochondrial enzymes were found to be decreased, when compared to the control group. The levels of kidney functional markers (urea, uric acid and creatinine) were also found to be abnormal in serum of bromobenzene alone treated rats. On the other hand, administration of W. somnifera (250 and 500 mg/kg) along with bromobenzene offered a significant dose-dependent protection to the biochemical alterations as observed in the bromobenzene alone treated rats, which was also evidenced by histopathology. CONCLUSION: Thus, the oral administration of W. somnifera significantly protected against the bromobenzene induced nephrotoxicity and renal mitochondrial dysfunction in rats.