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Journal of the American College of Nutrition, Vol. 27, No. 2, 299-305 (2008)
Published by the American College of Nutrition

Prevention and Reversion of Nonalcoholic Steatohepatitis in OB/OB Mice by S-Nitroso-N-Acetylcysteine Treatment

Claudia P. M. S. de Oliveira, MD, Vicência M. R. de Lima, Fernanda I. Simplicio, Francisco G. Soriano, MD, Evandro S. de Mello, MD, Heraldo P. de Souza, MD, Venâncio A. F. Alves, MD, Francisco R. M. Laurindo, MD, Flair J. Carrilho, MD and Marcelo G. de Oliveira

Departments of Gastroenterology (C.P.M.S.d.O., V.M.R.d.L., F.J.C.)
Emergency (F.G.S., H.P.d.S.)
Pathology (E.S.d.M., V.A.F.A.)
Heart Institute (H.P.d.S., F.R.M.L.), University of São Paulo School of Medicine (USP), São Paulo, SP, Br
Institute of Chemistry (F.I.S., M.G.d.O.), State University of Campinas (UNICAMP), Campinas, SP, BRAZIL

Address reprint requests to: C P M S Oliveira, M.D., Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de São Paulo, 9° andar, sala 9159, Av. Dr Enéas de Carvalho Aguiar n° 255, Instituto Central, 05403000 São Paulo, BRASIL. E-mail: cpm{at}usp.br

Objective: To evaluate the role oral administration of S-nitroso-N-acetylcysteine (SNAC), a NO donor drug, in the prevention and reversion of NASH in two different animal models.

Methods: NASH was induced in male ob/ob mice by methionine-choline deficient (MCD) and high-fat (H) diets. Two animal groups received or not SNAC orally for four weeks since the beginning of the treatment. Two other groups were submitted to MCD and H diets for 60 days receiving SNAC only from the 31st to the 60th day.

Results: SNAC administration inhibited the development of NASH in all groups, leading to a marked decrease in macro and microvacuolar steatosis and in hepatic lipid peroxidation in the MCD group. SNAC treatment reversed the development of NASH in animals treated for 60 days with MCD or H diets, which received SNAC only from the 31st to the 60th day.

Conclusions: Oral administration of SNAC markedly inhibited and reversed NASH induced by MCD and H diets in ob/ob mice.

Key words: NASH, oxidative stress, S-nitroso-N-acetylcysteine, nitric oxide






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