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-α), interleukin-1 (IL-1β), IL-6, IL-10 and interferon-gamma (IFN-γ) 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-α, IL-1β and IFN-γ 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-α, IL-1β and IFN-γ 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.
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-α), interleukin-1 (IL-1β), IL-6, IL-10 and interferon-gamma (IFN-γ) 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-α, IL-1β and IFN-γ 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-α, IL-1β and IFN-γ 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.
Authors: Mustafa Derda Kaya; Eralp Başer; Sibel Kaya; Mustafa Kemal Takal; Feride Sahin; Esra Kuşçu; Filiz Yanık Journal: J Turk Ger Gynecol Assoc Date: 2014-03-01
Authors: Stefan Markovic; Anne Fages; Tangi Roussel; Ron Hadas; Alexander Brandis; Michal Neeman; Lucio Frydman Journal: Proc Natl Acad Sci U S A Date: 2018-02-14 Impact factor: 11.205
Authors: Jose Sergio Possomato-Vieira; Victor Hugo Gonçalves-Rizzi; Tamiris Uracs Sales Graça; Regina Aparecida Nascimento; Carlos A Dias-Junior Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2016-09-12 Impact factor: 3.000