Evaluation of protective efectiveness of pyrrolidine dithiocarbamate, inhibitor of nf?b on pyrrolizidine alcaloids induced hepatotoxicity

OBJECT: The aim of the present study was to examine the efficacy of the pyrrolidine dithiocarbamate (PDTC), an antioxidant and inhibitor of the NF-?B activation, in monocrotaline (MCT) induced liver injury.MATERIAL AND METHOD: In this study, rats randomized into four groups: 1.Control group, 2. MCT-injected rats (60 mg/kg MCT i.p) 3. MCT-injected rats treated with PDTC 100 mg/kg once daily i.p on days 3 to 28 (MCT+PDTC group) 4. PDTC injected group (100 mg/kg/day i.p on days 3 to 28). All rats were sacrificed after 28 days. Their livers are taken out four histologic and biochemical studies. It is detected MDA levels and TAS by commercially available ImAnOx kit on the removed tissue. For light microscobic analysis, the tissues are hold in formol %10 and after routine following intered in paraffin and examined by dying HE and Gomori triple dying method.FINDINGS: We observed that MDA levels were elevated (from 0.012±0.0008 nmol/mg protein to 0.017±0.0004 nmol/mg protein n=6) and TAS was not changed significantly (from 0.58±0.03 µmol/mg protein to 0.50±0.02 µmol/mg protein, n=6) by MCT. In contrast to the MCT-injected group, MDA levels were significantly decreased in the MCT+PDTC treated group (0.011±0.0004 nmol/mg protein, n=6). TAS was significantly higher in MCT+PDTC treated rats when compared to MCT injected rats (from 0.50±0.03 µmol/mg protein to 0.70±0.10 µmol/mg protein n=6). Histopathological examination demonstrated that PDTC decreased significantly hemorrhage-congestion, inflamation, collagen deposition, steatozis, karyomegaly and pyknosis in MCT treated rats. (We do not observed any significant differences between PDTC and control group)DISCUSION AND CONCLUSIONS: In conclusion, it has been shown that ROS participate in MCT-induced liver injury. The free radical-scavenging properties of PDTC an NF-?B inhibitor, are the basis of decreased inflammation and protected liver parenchyma in MCT treated liver. Therefore, we conclude that PDTC reduces the development of MCT induced liver damage.Keywords: Liver, MCT, NF?B, PDTC