title: Toxicological evaluation of Terminalia paniculata bark extract and its protective effect against CCl4-induced liver injury in rodents.
abstract: BACKGROUND
  Based on the reported antioxidant and anti-inflammatory potential of Terminalia paniculata, the bark aqueous extract (TPW) was investigated against liver damage.
  
  
  METHODS
  Intrinsic cytotoxicity was tested on normal human liver (Chang) cell lines, followed by acute and sub-chronic toxicity studies in mice. TPW was then evaluated against CCl4-induced liver toxicity in rats. Liver enzymes (AST, ALT, and ALP) and antioxidant markers were assessed. The effect of TPW on isolated hepatic cells, post-CCl4 administration, was assessed by isolated mitochondrial membrane staining. The actions of TPW on apoptotic pathway in CCl4-treated Chang cells were also elucidated.
  
  
  RESULTS
  TPW was found to be safe at all doses tested in both in vitro and in vivo toxicity studies. TPW (400 mg/kg, p.o.) significantly (*p <0.05) improved liver enzyme activity as compared to CCl4. Also, it improved antioxidant status (GSH, GST, MDA and total thiol) and preserved hepatic cell architecture. TPW pre-treatment significantly attenuated the levels of phospho-p53, p53, cleaved caspase-3, phospho-Bad, Bad and cleaved PARP in CCl4-treated Chang cells, improving the viability considerably.
  
  
  CONCLUSIONS
  The findings support a protective role for Terminalia paniculata in pathologies involving oxidative stress.
authors.forename: Sahil
authors.initials: S
authors.lastname: Talwar
authors.forename: Hitesh V
authors.initials: HV
authors.lastname: Jagani
authors.forename: Pawan G
authors.initials: PG
authors.lastname: Nayak
authors.forename: Nitesh
authors.initials: N
authors.lastname: Kumar
authors.forename: Anoop
authors.initials: A
authors.lastname: Kishore
authors.forename: Punit
authors.initials: P
authors.lastname: Bansal
authors.forename: Rekha R
authors.initials: RR
authors.lastname: Shenoy
authors.forename: Krishnadas
authors.initials: K
authors.lastname: Nandakumar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002251:Carbon Tetrachloride; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D029766:Terminalia / Q000009:adverse effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D010936:Plant Extracts; D002251:Carbon Tetrachloride; D053148:Caspase 3