Assessment of the effectiveness of nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in the treatment of pulmonary hypertension

Pulmonary hypertension (PH) is a fatal disorder that is associated with oxidative stress, structural changes and inflammatory responses in the pulmonary vasculature. In this study, we aimed to investigate the potential protective effects of pyrrolidine dithiocarbamate (PDTC) as an antioxidant and anti-inflammatory agent on monocrotaline (MCT)-induced pulmonary hypertension.Adult male rats randomized into three groups: 1. Control group, 2. MCT-injected rats (60 mg/kg MCT i.p) 3. MCT-injected rats treated with NF-?B inhibitor PDTC (100 mg/kg once daily i.p on days 3 to 28 (the MCT/PDTC group) All rats were sacrificed after 28 days. The MCT-induced increase in right ventricle to left ventricle plus septum weight ratio (from 0,24 ? 0,01 to 0,33 ? 0,01, p<0.05, n=6) was reduced significantly in the MCT+PDTC-treated group (0,26 ? 0,02, p<0.05, n=6). MDA levels were elevated (from 0,022 ? 0,001 ? mol/mg protein to 0,031 ? 0,001 ? mol/mg protein, p<0.05, n=6) and total antioxidant status was not changed significantly (from 0,78 ? 0,06 ? mol/mg protein to 0,80 ? 0,03 ? mol/mg protein, p<0.05, n=6) by MCT. In contrast to the MCT-injected group, MDA levels were significantly decreased in the MCT+PDTC-treated group (0,026 ? 0,002, p<0.05, n=6). Total antioxidant status (0,91 ? 0,06 ? mol/mg protein, p<0.05, n=6) was significantly higher in MCT+PDTC-treated rats when compared to pulmonary hypertensive rats. Histopathological examination demonstrated that PDTC treatment reduced the development of inflammation, hemorrhages and congestion, attenuated collagen deposition in MCT-induced PH. In conclusion, our research suggest that NF-?B plays a primary role in the pathogenesis of PH and represent a new target for therapeutic intervention in PH.Keywords: NF-?B, PDTC, pulmonary hypertension