title: Deleterious effects of 28-day oral co-administration of first-line anti-TB drugs on spleen, blood and bone marrow chromosomes in normal rat.
abstract: BACKGROUND
  Isoniazid, rifampicin and pyrazinamide are most reliable and cost-effective remedy for tuberculosis treatment and prophylaxis among first-line anti-tuberculosis (TB) drugs and have a pronounced tendency to cause adverse drug reactions. Hepatotoxicity is well-studied side effect of these drugs but their effects on other organs like spleen and blood are still needed to be explored.
  
  
  OBJECTIVE
  To explore the probable outcome of co-administration these three major antitubercular drugs (ATDs), rifampicin, isoniazid and pyrazinamide on spleen, blood and bone marrow.
  
  
  METHODS
  Different parameters were evaluated like lipid peroxidation, glutathione (GSH) and protein content in spleen by spectrophotometric evaluation, hematological evaluation by determining total hemoglobin, total leukocyte count, differential leukocyte count and scanning electron microscopy studies in blood, genotoxicity studied by bone marrow chromosomal analysis and DNA fragmentation. The female rats n = 12 (150-200 g) were grouped as control group orally given saline and toxicant group given INH (30.85 mg/kg b.wt.) + RIF (61.7 mg/kg b.wt.) + PZA (132.65 mg/kg b.wt.) dosage extrapolated from dose that is used in human for 28 d once daily.
  
  
  RESULTS
  After 28 d-oral co-administration of anti-TB drugs (INH (30.85 mg/kg b.wt.) + RIF (61.7 mg/kg b.wt.) + PZA (132.65 mg/kg b.wt.)), it was revealed that there were an increase thiobarbituric acid reactive substances, decrease in GSH and protein contents in spleen. Marked changes in hematological parameters, DNA fragmentation and chromosomes were also observed.
  
  
  CONCLUSIONS
  This can be concluded from this work that co-administration of first-line ATDs is toxic to spleen and blood also these drugs can cause damage at genetic level.
authors.affiliation: a Cytogenetics Laboratory, Department of Zoology, Panjab University , Chandigarh , India.
authors.forename: Radhika
authors.initials: R
authors.lastname: Sharma
authors.affiliation: a Cytogenetics Laboratory, Department of Zoology, Panjab University , Chandigarh , India.
authors.forename: Vijay L
authors.initials: VL
authors.lastname: Sharma
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004249:DNA Damage; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007538:Isoniazid / Q000008:administration & dosage / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D009152:Mutagenicity Tests; D011718:Pyrazinamide / Q000008:administration & dosage / Q000633:toxicity*; D017208:Rats, Wistar; D012293:Rifampin / Q000008:administration & dosage / Q000633:toxicity*; D018570:Risk Assessment; D013154:Spleen / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; D017392:Thiobarbituric Acid Reactive Substances; D011718:Pyrazinamide; D005978:Glutathione; D007538:Isoniazid; D012293:Rifampin
keywords: Spleen; antioxidants; genotoxicity; histopathology; scanning electron microscopy