title: Hepatoprotective activity of six polyherbal formulations in paracetamol induced liver toxicity in mice.
abstract: OBJECTIVE
  Polyherbal formulations available with a wide range of indications like protective to liver, appetite and growth promoters, gastrointestinal and hepatic regulator, as treatment for hepatic dysfunction, for hepatic regeneration as well as liver stimulant and tonic. Despite the widespread use, there is a lack of scientific evidence on their efficacy and safety. This study was undertaken to evaluate the hepatoprotective activity of six commercially available formulations, namely Liv 52, Livergen, Livokin, Octogen, Stimuliv and Tefroliv in acute liver toxicity in mice model induced by paracetamol (PCM).
  
  
  METHODS
  Swiss albino mice of either sex were used, divided in 28 groups with six in each group. The dose of the polyherbal formulations was calculated from human dose (20 ml/day) using a standard conversion table. They were given as pretreatment (2.60 ml/kg/day) for 7 days by oral route twice a day prior to PCM administration. Hepatotoxicity was induced by administering a single oral dose of PCM (500 mg/kg bw) on day 8. The study parameters were conducted on day 9. The biochemical parameters included liver enzyme levels alanine tranaminases (ALT), aspartate transaminases (AST) and alkaline phosphatase (ALP). The pharmacological and pathological parameters were phenobarbitone sleeping time and macroscopic and microscopic changes of liver tissues respectively.
  
  
  RESULTS
  PCM toxicity significantly increased ALT, AST and ALP (321.00 +/- 87.93, 273.17 +/- 45.68, 257.50 +/- 17.64 IU/l vs normal control, 33.33 +/- 0.61, 89.33 +/- 9.50, 152.17 +/- 11.40 IU/l respectively, P<0.05), prolonged phenobarbitone induced sleeping time (from 277.50 +/- 8.04 min to 335.83 +/- 7.00 min, P<0.05). When PCM higher dose (1g/kg p.o. single dose) was used, the liver tissue, in macroscopic appearance, showed extensive necrosis associated with haemorrhages. Low dose (500 mg/kg p.o. single dose) showed punctate haemorrhagic necrosis of liver tissue. In the microscopic studies, PCM induced toxicity showed haemorrhages, fatty changes and necrosis. The pretreatment in low doses (2.6 ml/kg/day) with liquid formulations of Liv 52 and Livergen reversed the PCM induced liver toxicity. At higher doses (5.2 ml/ kg/day), all the six herbal formulations conclusively showed marked beneficial effects in the studied pharmacological, biochemical and histological parameters.
  
  
  CONCLUSIONS
  The present findings demonstrated the efficacy of polyherbal liquid formulations at two dose levels in PCM induced hepatotoxicity in mice. However, it suggests that a dose adjustment may be necessary to optimize the effects in clinical settings.
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India.
authors.forename: C
authors.initials: C
authors.lastname: Girish
authors.forename: B C
authors.initials: BC
authors.lastname: Koner
authors.forename: S
authors.initials: S
authors.lastname: Jayanthi
authors.forename: K R
authors.initials: KR
authors.lastname: Rao
authors.forename: B
authors.initials: B
authors.lastname: Rajesh
authors.forename: S C
authors.initials: SC
authors.lastname: Pradhan
mesh_terms: D000082:Acetaminophen / Q000633:toxicity; D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D008099:Liver / Q000187:drug effects*; D008419:Materia Medica / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D004338:Drug Combinations; D008419:Materia Medica; D010936:Plant Extracts; C081215:stimuliv; D000082:Acetaminophen; C002614:Liv 52; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase