PMID- 22781706 OWN - NLM STAT- MEDLINE DCOM- 20121022 LR - 20181201 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 91 IP - 5-6 DP - 2012 Sep 4 TI - Hepatoprotective and anti-inflammatory effects of silibinin on experimental preeclampsia induced by L-NAME in rats. PG - 159-65 LID - 10.1016/j.lfs.2012.06.036 [doi] AB - AIMS: Inhibition of nitric oxide synthase with N-omega-nitro-l-arginine methyl ester (l-NAME) has been employed as an experimental model of human preeclampsia. This study determined the protective effect of silibinin, a flavonoid with anti-inflammatory and hepatoprotective properties on the deleterious effects observed in experimentally induced preeclampsia in rats. MAIN METHODS: Pregnant Wistar rats were treated during gestation (days 10-20) with l-NAME (70-80mg/kg/day) in drinking water or with l-NAME plus silibinin (100mg/kg/day, orally) starting at day 0, day 7 or day 14 of pregnancy. Systolic blood pressure was recorded from gestation days 0 to 21. A control group of pregnant non-treated rats was analyzed similarly. On day 21 the rats were euthanized and the following parameters were evaluated: proteinuria, platelet count, liver histopathology and reproductive outcome. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1beta), IL-6, IL-10 and interferon-gamma (IFN-gamma) were determined in liver homogenate by enzyme immunoassay. KEY FINDINGS: In comparison with the l-NAME group the silibinin treatment reduced the values of systolic blood pressure, proteinuria, TNF-alpha, IL-1beta and IFN-gamma in liver, normalized the platelet count and improved fetal outcomes. Histopathological lesions in liver of the l-NAME group showed intense mononuclear inflammatory infiltrate and thickening of muscle tunica of arterial vessel, mainly in the periportal area. Silibinin treatment induced attenuation of periportal inflammatory infiltrate, showing an association between inflammatory infiltrate and TNF-alpha, IL-1beta and IFN-gamma levels in liver homogenate. SIGNIFICANCE: Silibinin administration to l-NAME-treated rats displays anti-inflammatory and immunomodulatory actions that may contribute to its hepatoprotective effects and improve reproductive outcomes in experimental preeclampsia. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Souza, Camila Oliveira de AU - Souza CO AD - Department of Gynecology and Obstetrics, Botucatu Medical School, Sao Paulo State University, Botucatu, Sao Paulo, SP, Brazil. FAU - Peracoli, Maria Terezinha Serrao AU - Peracoli MT FAU - Weel, Ingrid Cristina AU - Weel IC FAU - Bannwart, Camila Ferreira AU - Bannwart CF FAU - Romao, Mariana AU - Romao M FAU - Nakaira-Takahagi, Erika AU - Nakaira-Takahagi E FAU - Medeiros, Leonardo Teixeira Lopes de AU - Medeiros LT FAU - Silva, Marcia Guimaraes da AU - Silva MG FAU - Peracoli, Jose Carlos AU - Peracoli JC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120707 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Immunologic Factors) RN - 0 (Protective Agents) RN - 0 (Silymarin) RN - 4RKY41TBTF (Silybin) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Blood Pressure/drug effects MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Immunologic Factors/pharmacology MH - Inflammation/*drug therapy/physiopathology MH - Liver/*drug effects/pathology MH - NG-Nitroarginine Methyl Ester MH - Pre-Eclampsia/*drug therapy MH - Pregnancy MH - Protective Agents/pharmacology MH - Rats MH - Rats, Wistar MH - Silybin MH - Silymarin/*pharmacology EDAT- 2012/07/12 06:00 MHDA- 2012/10/23 06:00 CRDT- 2012/07/12 06:00 PHST- 2011/09/01 00:00 [received] PHST- 2012/05/31 00:00 [revised] PHST- 2012/06/25 00:00 [accepted] PHST- 2012/07/12 06:00 [entrez] PHST- 2012/07/12 06:00 [pubmed] PHST- 2012/10/23 06:00 [medline] AID - S0024-3205(12)00344-X [pii] AID - 10.1016/j.lfs.2012.06.036 [doi] PST - ppublish SO - Life Sci. 2012 Sep 4;91(5-6):159-65. doi: 10.1016/j.lfs.2012.06.036. Epub 2012 Jul 7.