Deneysel karaciğer fibrozisinde peginterferon alfa2b ve taurin tedavilerinin spontan gerilemeye katkısının in-vivo ve in-vitro değerlendirilmesi
Özet
S3 SUMMARY Evaiution of In vitro and In vivo Effects of Pegyiated interferon Alfa 2b and Taurine Treatments on Spontaneous Recovery in Experimental Liver Fibrosis Fibrosis, a frequent complication of chronic liver diseases is characterized by overproduction (fibrogenesis) and diminished degradation of matrix proteins (fibronolysis) in the sinusoids. It ultimately progresses to cirrhosis which is a common cause of mortality worldwide. Main cells that produce excess matrix are hepatic stellate cells (HSC). Antifibrotic treatment strategies have been being directed not only to direct interference with intracellular events of these cells but also on correction of altered signaling between HSCs and hepatocytes, other non parenchymal cells and collagen matrix. We studied the effects of peginterferonct2b, a newly modified lnterferona molecule with higher sustained antiviral response rates, and a potent antioxidant taurins on experimental liver fibrosis. Sixty male Sprague-Dawley rats were injected SC with CCI4 for 12 weeks to induce liver fibrosis. Then, hepatotoxin induction was stopped and the rats were divided into four groups. Group I (n=15) was left for spontaneous recovery. Group II was treated with peginterferona2b 1.5ug/kg/week, Group III with taurin 1200 mg/kg/day, and Group IV with the combination of these two regimens. After four weeks of treatment ail the rats were killed and histopathological fibrosis scores, a SMA (+) HSH counts, oxidative stress parameters, apoptotic hepatocytes and HSCs were determined. Individual effects of the two agents on in vitro HSC proliferation were analyzed on isolated celis.84 Peginterferon,. and taurin equally improved fibrosis. Fibrosis scores were reduced significantly in Group I, II and III when compared to Group I (p<0,001). Scores were lower in Group IV than Group II and III but the difference was not significant (p>0,05). As the indication of activation, a SMA (+) cell counts were reduced Group II, III and İV when compared to Group I (p<0,001). Group IV a SMA (+) ceil counts were lower than Group III (p<0,03). a SMA (+) ceil counts were significantly low in Group III than Group I (p<0,001). Number of a SMA (+) ceils in Group II and three were similar. Peginterferon,, did not effect hepatocyte apoptosis. Taurin alone and its combination induced hepatocyte apoptosis significantly (p<0,03, p<0,001, respectively). Effects of peginterferon,, and taurin on hepatocyte apoptosis were similar. HSC apoptosis increased significantly in Group II, III and IV when compared to Group I (p<0,03, p<0,002, p<0,001, respectively). Combination regimen (Group IV) significantly increased HSC apoptosis in comparison with individual peginterferona and taurin treatments (p<0,02, p<0,001, respectively). There was no difference between apopiotic ceii counts in Group II and Mi (p>0.05). Tissue SOD, MDA and GSHPx levels improved significantly in taurine treated Group III. Peginterferon,, inhibited isolated HSC proliferation at 10, 50 and 100 ng/mi concentrations at 24, 48 ve 72nd hour time points. The maximal effect occurred at 72nd hour. Taurine also inhibited HSC proliferation at concentration of 1. 5, 10, 20, 50 and 100 mmoi/L at 24, 48 and 72nd hour directly proportional with the time. In conclusion, peginterferon a and taurine both has improving effects on experimental liver fibrosis. Although seems favorable, combination of these two has no significant benefit. Key Words:Liver fibrosis, Peg IFNcuh, Taurin