Naslov
Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice

Autori
Domitrović, Robert ; Škoda, Marko ; Vasiljev Marchesi, Vanja ; Cvijanović, Olga ; Pernjak Pugel, Ester ; Bival Štefan, Maja

Izvornik
Food and chemical toxicology (0278-6915) 51 (2013); 370-378

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
rosmarinic acid; hepatotoxicity; oxidative/nitrosative stress; inflammation; apoptosis; liver fibrosis

Sažetak
The aim of this study was to investigate the therapeutic potential of rosmarinic acid (RA), a natural phenolic compound, in the treatment of acute liver toxicity. RA at doses of 10, 25 and 50 mg/kg was administered orally once daily for 2 consecutive days, 6 h after CCl4 intoxication. CCl4 intoxication caused a severe hepatic necrosis and increased serum ALT activity. In the livers, oxidative/nitrosative stress was evidenced by increased 3-nitrotyrosine (3-NT) formation and a significant decrease in Cu/Zn superoxide dismutase (SOD) activity. CCl4 administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). RA improved histological and serum markers of liver damage and significantly ameliorated oxidative/nitrosative stress and inflammatory response in liver tissue. Additionally, RA prevented tumor growth factor-beta1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) expression, suggesting suppression of profibrotic response. Furthermore, RA significantly inhibited the CCl4-induced apoptosis, which was evident from decreased cleavage of caspase-3. The hepatoprotective activity of RA coincided with the amelioration of NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. The results of this study indicates that RA possesses antioxidant, anti-inflammatory, antiapoptotic and antifibrotic activity against acute liver toxicity.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA