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Pentoxifylline attenuates steatohepatitis induced by the methionine choline deficient diet.
J Hepatol. 2004 Oct; 41(4):592-8.JH

Abstract

BACKGROUND/AIMS

Feeding mice a methionine choline deficient (MCD) diet serves as a nutritional model of non-alcoholic steatohepatitis (NASH). NASH and alcohol-induced steatohepatitis are histologically similar, suggesting a similar pathogenesis. Pentoxifylline (PTX) attenuates TNF-alpha production, acts as an antioxidant and decreases mortality in alcoholic steatohepatitis. The aim of our study is to determine if PTX attenuates MCD diet induced steatohepatitis and determine the mechanism of this effect.

METHODS

Mice were placed on an MCD or control diet for 2 weeks and were treated with or without PTX. Serum ALT, liver histology, and inflammatory mechanisms were evaluated.

RESULTS

PTX attenuates MCD diet induced steatohepatitis, decreasing both serum ALT levels and hepatic inflammation. Serum ALT levels were reduced approximately 50% in the MCD+PTX group compared to the MCD group. Hepatic glutathione levels were significantly higher in the MCD+PTX group compared to the MCD group. There was also a reduction in TNF-alpha mRNA in female mice treated with PTX. MCD+PTX mice had increased hepatic triglyceride content compared to the MCD mice, but less histologic evidence of inflammation despite the increased steatosis. Serum lipid and bile salt levels also were similar in PTX and vehicle control treated mice.

CONCLUSIONS

PTX decreases serum ALT levels and hepatic inflammation in the MCD model of steatohepatitis, likely via increasing glutathione levels or reducing TNF-alpha expression.

Authors+Show Affiliations

Department of Medicine, Division of Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15464239

Citation

Koppe, Sean W P., et al. "Pentoxifylline Attenuates Steatohepatitis Induced By the Methionine Choline Deficient Diet." Journal of Hepatology, vol. 41, no. 4, 2004, pp. 592-8.
Koppe SW, Sahai A, Malladi P, et al. Pentoxifylline attenuates steatohepatitis induced by the methionine choline deficient diet. J Hepatol. 2004;41(4):592-8.
Koppe, S. W., Sahai, A., Malladi, P., Whitington, P. F., & Green, R. M. (2004). Pentoxifylline attenuates steatohepatitis induced by the methionine choline deficient diet. Journal of Hepatology, 41(4), 592-8.
Koppe SW, et al. Pentoxifylline Attenuates Steatohepatitis Induced By the Methionine Choline Deficient Diet. J Hepatol. 2004;41(4):592-8. PubMed PMID: 15464239.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pentoxifylline attenuates steatohepatitis induced by the methionine choline deficient diet. AU - Koppe,Sean W P, AU - Sahai,Atul, AU - Malladi,Padmini, AU - Whitington,Peter F, AU - Green,Richard M, PY - 2004/02/24/received PY - 2004/06/10/revised PY - 2004/06/25/accepted PY - 2004/10/7/pubmed PY - 2005/3/4/medline PY - 2004/10/7/entrez SP - 592 EP - 8 JF - Journal of hepatology JO - J. Hepatol. VL - 41 IS - 4 N2 - BACKGROUND/AIMS: Feeding mice a methionine choline deficient (MCD) diet serves as a nutritional model of non-alcoholic steatohepatitis (NASH). NASH and alcohol-induced steatohepatitis are histologically similar, suggesting a similar pathogenesis. Pentoxifylline (PTX) attenuates TNF-alpha production, acts as an antioxidant and decreases mortality in alcoholic steatohepatitis. The aim of our study is to determine if PTX attenuates MCD diet induced steatohepatitis and determine the mechanism of this effect. METHODS: Mice were placed on an MCD or control diet for 2 weeks and were treated with or without PTX. Serum ALT, liver histology, and inflammatory mechanisms were evaluated. RESULTS: PTX attenuates MCD diet induced steatohepatitis, decreasing both serum ALT levels and hepatic inflammation. Serum ALT levels were reduced approximately 50% in the MCD+PTX group compared to the MCD group. Hepatic glutathione levels were significantly higher in the MCD+PTX group compared to the MCD group. There was also a reduction in TNF-alpha mRNA in female mice treated with PTX. MCD+PTX mice had increased hepatic triglyceride content compared to the MCD mice, but less histologic evidence of inflammation despite the increased steatosis. Serum lipid and bile salt levels also were similar in PTX and vehicle control treated mice. CONCLUSIONS: PTX decreases serum ALT levels and hepatic inflammation in the MCD model of steatohepatitis, likely via increasing glutathione levels or reducing TNF-alpha expression. SN - 0168-8278 UR - https://www.unboundmedicine.com/medline/citation/15464239/Pentoxifylline_attenuates_steatohepatitis_induced_by_the_methionine_choline_deficient_diet_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(04)00283-1 DB - PRIME DP - Unbound Medicine ER -