PMID- 22320165 OWN - NLM STAT- MEDLINE DCOM- 20130903 LR - 20181202 IS - 1439-0396 (Electronic) IS - 0931-2439 (Linking) VI - 97 IP - 2 DP - 2013 Apr TI - Hepatoprotective effects of S-adenosylmethionine and silybin on canine hepatocytes in vitro. PG - 331-41 LID - 10.1111/j.1439-0396.2012.01275.x [doi] AB - Inflammation and oxidative stress are associated with liver injury and development of liver disease. The transcription factors nuclear factor-kappa beta (NF-kappaB) and nuclear factor erythroid 2-related factor 2 (Nrf2) play critical roles in modulating liver injury and damage. Activation of NF-kappaB induces production of pro-inflammatory molecules including prostaglandin E2 (PGE2 ), interleukin-8 (IL-8) and macrophage chemotactic protein-1 (MCP-1). Nrf2 regulates genes controlling antioxidants. Our laboratory previously showed that hepatocytes, the primary functional cell type comprising liver tissue, respond to the cytokine interleukin-1 beta (IL-1beta) by increased production of PGE2 , IL-8 and MCP-1. This increase is associated with nuclear translocation of NF-kappaB. In this study, we evaluated whether primary canine hepatocytes pre-treated with the combination of S-adenosylmethionine (SAMe; 30 and 2000 ng/ml) and silybin (SB; 298 ng/ml), agents with known anti-inflammatory and antioxidant properties, could attenuate IL-1beta-induced inflammation and oxidative stress. The SAMe and SB combination reduced cytokine-induced PGE2 , IL-8 and MCP-1 production while also inhibiting NF-kappaB nuclear translocation. These changes were accompanied by increased antioxidant enzyme-reduced glutathione (GSH) comparable to control levels. The study shows for the first time that the SAMe and SB combination inhibits both inflammation and oxidative stress through two separate signalling pathways. CI - (c) 2012 Blackwell Verlag GmbH. FAU - Au, A Y AU - Au AY AD - Research and Development, Nutramax Laboratories, Inc., 2208 Lakeside Blvd., Edgewood, MD 21040, USA. FAU - Hasenwinkel, J M AU - Hasenwinkel JM FAU - Frondoza, C G AU - Frondoza CG LA - eng PT - Journal Article DEP - 20120209 PL - Germany TA - J Anim Physiol Anim Nutr (Berl) JT - Journal of animal physiology and animal nutrition JID - 101126979 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Biomarkers) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-8) RN - 0 (Silymarin) RN - 4RKY41TBTF (Silybin) RN - 7LP2MPO46S (S-Adenosylmethionine) RN - GAN16C9B8O (Glutathione) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Antioxidants/*pharmacology MH - Biomarkers MH - Cell Survival/drug effects MH - Cells, Cultured MH - Chemokine CCL2/genetics/metabolism MH - Dinoprostone/genetics/metabolism MH - Dogs MH - Gene Expression Regulation/drug effects MH - Glutathione/metabolism MH - Hepatocytes/cytology/*drug effects MH - Interleukin-1beta/pharmacology MH - Interleukin-8/genetics/metabolism MH - Oxidative Stress MH - S-Adenosylmethionine/*pharmacology MH - Silybin MH - Silymarin/*pharmacology EDAT- 2012/02/11 06:00 MHDA- 2013/09/04 06:00 CRDT- 2012/02/11 06:00 PHST- 2012/02/11 06:00 [entrez] PHST- 2012/02/11 06:00 [pubmed] PHST- 2013/09/04 06:00 [medline] AID - 10.1111/j.1439-0396.2012.01275.x [doi] PST - ppublish SO - J Anim Physiol Anim Nutr (Berl). 2013 Apr;97(2):331-41. doi: 10.1111/j.1439-0396.2012.01275.x. Epub 2012 Feb 9.