Hepatoprotective and anti-inflammatory effects of silibinin on experimental preeclampsia induced by L-NAME in rats.
OBJECTIVE
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.


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.


RESULTS
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.


CONCLUSIONS
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.
Department of Gynecology and Obstetrics, Botucatu Medical School, São Paulo State University, Botucatu, São Paulo, SP, Brazil.
Camila Oliveira de
CO
Souza
Maria Terezinha Serrão
MT
Peraçoli
Ingrid Cristina
IC
Weel
Camila Ferreira
CF
Bannwart
Mariana
M
Romão
Erika
E
Nakaira-Takahagi
Leonardo Teixeira Lopes de
LT
Medeiros
Márcia Guimarães da
MG
Silva
José Carlos
JC
Peraçoli
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester; D011225:Pre-Eclampsia / Q000188:drug therapy*; D011247:Pregnancy; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D020011:Protective Agents; D012838:Silymarin; D000077385:Silybin; D019331:NG-Nitroarginine Methyl Ester