title: ACTION OF VITAMIN E ON EXPERIMENTAL SEVERE ACUTE LIVER FAILURE.
abstract: BACKGROUND
  Severe Acute Liver Failure (ALF) is a life-threatening clinical syndrome characterized by hepatocyte necrosis, loss of hepatic architecture, and impairment of liver functions. One of the main causes of ALF is hepatotoxicity from chemical agents, which damage hepatocytes and result in increase of reactive oxygen species. The vitamin E isoform is the one with the strongest biological antioxidant activity.
  
  
  OBJECTIVE
  To evaluate the antioxidant effect of vitamin E in this ALF model.
  
  
  METHODS
  We used 56 rats (mean weight of 300 g) divided into eight groups, four groups assessed at 24 hours and 4 assessed at 48 hours after induction: control group (CO); Vitamin E (Vit. E); Thioacetamide (TAA) and Thioacetamide + Vitamina E (TAA+Vit.E). Rats were submitted to injections of thioacetamide (400 mg/kg i.p.) at baseline and 8 hours later. Vitamin E (100 mg/kg ip) was administered 30 minutes after the second dose of thioacetamide. The 48-hour group rats received two additional doses of vitamin E (24h and 36h). At 24h or 48 hours after the administration of the first dose of TAA, rats were weighed and anesthetized and their blood sampled for evaluation of liver integrity through enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Liver tissue was sampled for assessment of lipid peroxidation (LPO) by the technique TBARS, antioxidant enzymes SOD, CAT, GPx and GST activity, levels of the NO 2 /NO 3 and histology by H&E in two times. The results were expressed as mean ± standard deviation and statistically analyzed by ANOVA followed by Student-Newman-Keuls, with P <0.05 considered as significant.
  
  
  RESULTS
  After treatment with vitamin E, we observed a reduction in liver enzymes AST (U/L) (101.32±19.45 in 24 hours and 97.85±29.65 in 48 hours) related to the TAA group (469.56± 0.69 in 24 hours and 598.23±55.45 in 48 hours) and ALT (U/L) (76.59±8.56 in 24 hours and 68.47±6.49 in 48 hours) compared to the TAA group (312.21±10.23 in 24 hours and 359.15±17.58 in 48 hours). There was a reduction of LPO (nmol/mg Prot) in the TAA+Vit.E group (0.77±0.07 in 24 hours and 0.95±0.08 in 48 hours) compared to the TAA group (1.50±0.07 in 24 hours e 1.65±0.16 in 48 hours). SOD decreased in the TAA+Vit.E group (49.48±9.47 in 24 hours and 62.45±18, 47 in 48 hours), related to the TAA group (98.46±15.48 in 24 hours and 154.13±21.46 in 48 hours), as well as GST (nmol/min/mg Prot) in the TAA+Vit.E group (350.57±36.93 in 24 hours and 453.29±13.84 in 48 hours) compared to the TAA group (561.57±64.56 in 24 hours and 673.43±38.13 in 48 hours). There was an increase in CAT (pmol/min/mg Prot) in the TAA+Vit.E group (3.40±0.44 in 24 hours and 3.0±0.35 in 48 hours) compared to the TAA group (1.65±0.21 in 24 hours and 1.86±0.42 in 48 hours). The GPx (nmol/min/mg Prot) increased in 24 hours in the TAA+Vit.E group (1.01±0.16) compared to the TAA group (0.41±0.04) and decreased in 48 hours (1.19±0.17) compared to the TAA group (1.76±0.21). There was a reduction in NO2/NO3 (mmol/L) levels in the TAA+Vit.E group (31.47±4.26 in 24 hours and 38.93±5.20 in 48 hours) compared to the TAA group (49.37±5.12 in 24 hours and 53.53±5.97 in 48 hours). The histopathological evaluation showed a decrease in liver injury (necrosis and inflammation) in both studied times.
  
  
  CONCLUSIONS
  These results suggest that vitamin E was able to protect the liver from lesions caused by thioacetamide.
authors.affiliation: Programa de Pós-Graduação BioSaúde, Universidade Luterana do Brasil, Canoas, RS, Brazil.|Laboratório de Estresse Oxidativo e Antioxidantes, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Fabiano Moraes
authors.initials: FM
authors.lastname: Miguel
authors.affiliation: Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Laboratório de Estresse Oxidativo e Antioxidantes, Universidade Luterana do Brasil, Canoas, RS, Brazil.|Laboratório de Hepatologia e Gastroenterologia Experimental, Hospital de Clínicas de Porto Alegre, RS, Brazil.
authors.forename: Elizângela Gonçalves
authors.initials: EG
authors.lastname: Schemitt
authors.affiliation: Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Laboratório de Estresse Oxidativo e Antioxidantes, Universidade Luterana do Brasil, Canoas, RS, Brazil.|Laboratório de Hepatologia e Gastroenterologia Experimental, Hospital de Clínicas de Porto Alegre, RS, Brazil.
authors.forename: Josieli Raskopf
authors.initials: JR
authors.lastname: Colares
authors.affiliation: Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Laboratório de Estresse Oxidativo e Antioxidantes, Universidade Luterana do Brasil, Canoas, RS, Brazil.|Laboratório de Hepatologia e Gastroenterologia Experimental, Hospital de Clínicas de Porto Alegre, RS, Brazil.
authors.forename: Renata Minuzzo
authors.initials: RM
authors.lastname: Hartmann
authors.affiliation: Programa de Pós-Graduação Pró-Saúde, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Morgan-Martins
authors.affiliation: Programa de Pós-Graduação BioSaúde, Universidade Luterana do Brasil, Canoas, RS, Brazil.|Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Programa de Pós-Graduação em Ciências Biológicas: Fisiologia Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Laboratório de Estresse Oxidativo e Antioxidantes, Universidade Luterana do Brasil, Canoas, RS, Brazil.|Laboratório de Hepatologia e Gastroenterologia Experimental, Hospital de Clínicas de Porto Alegre, RS, Brazil.
authors.forename: Norma Possa
authors.initials: NP
authors.lastname: Marroni
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D004195:Disease Models, Animal; D017114:Liver Failure, Acute / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012720:Severity of Illness Index; D014810:Vitamin E / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014810:Vitamin E; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase