Djelovanje miozmina na antioksidativne sustave u jetri štakora

Myosmine [3-(1-pyrrolin-2-yl) pyridine] is an alkaloid structurally similar to nicotine, which is known to induce oxidative stress. In this study we investigated the effects of myosmine on enzymatic and nonenzymatic antioxidative defence in rat liver. Wistar rats received a single i.p. injection of 19 mg kg-1 of myosmine and an oral dose of 190 mg kg-1 by gavage. Nicotine was used as a positive control. Through either route of administration, myosmine altered the hepatic function by decreasing the levels of reduced glutathione, superoxide dismutase, and glutathione peroxidase activities on one hand and by increasing malondialdehyde, catalase, and glutathione reductase activity on the other. Compared to control, both routes caused significant lipid peroxidation in the liver and altered hepatic enzymatic and non-enzymatic antioxidative defences. The pro-oxidant effects of myosmine were comparable with those of nicotine.Miozmin (3-(1-pirolin-2-il)piridin) alkaloid je strukturno sličan nikotinu, za koji se zna da potiče oksidativni stres. Istražili smo djelovanje miozmina na enzimske i neenzimske antioksidativne sustave u jetri štakora. Wistar štakori primili su jednokratno pokusni spoj intraperitonealno u dozi od 19 mg kg-1, odnosno na usta u dozi od 190 mg kg-1. Za pozitivnu kontrolu rabili smo nikotin. Nakon primjene, bez obzira na put, zamijećena je promjena u jetrenoj funkciji u obliku pada razina glutationa, aktivnosti superoksid dismutaze i glutation peroksidaze te rasta razina malondialdehida, aktivnosti katalaze i glutation reduktaze. Ovi nalazi upućuju na to da intraperitonealna i oralna primjena miozmina dovode do značajne lipidne peroksidacije u jetrenome tkivu te promjena u enzimskoj i neenzimskoj zaštiti jetre. Prooksidativno djelovanje miozmina pokazalo se sličnim onomu nikotina

Classical transient receptor potential 6 (TRPC6) channels support myofibroblast differentiation and development of experimental pulmonary fibrosis.

Pulmonary fibrosis (PF) is a chronic progressive lung disease without effective medical treatment options leading to respiratory failure and death within 3–5 years of diagnosis. The pathological process of PF is driven by aberrant wound-healing involving fibroblasts and myofibroblasts differentiated by secreted profibrotic transforming growth factor β (TGF-β1). Classical transient receptor potential 6 (TRPC6), a Na+- and Ca2 +-permeable cation channel, is able to promote myofibroblast conversion of primary rat cardiac and human dermal fibroblasts and TRPC6-deficiency impaired wound healing after injury. To study a potential role of TRPC6 in the development of PF we analyzed lung function, gene and protein expression in wild-type (WT) and TRPC6-deficient (TRPC6 −/−) lungs utilizing a bleomycin-induced PF-model. Fibrotic WT-mice showed a significant higher death rate while bleomycin-treated TRPC6-deficient mice were partly protected from fibrosis as a consequence of a lower production of collagen and an almost normal function of the respiratory system (reduced resistance and elastance compared to fibrotic WT-mice). On a molecular level TGF-β1 induced TRPC6 up-regulation, increased Ca2 + influx and nuclear NFAT localization in WT primary murine lung fibroblasts (PMLFs) resulting in higher stress fiber formation and accelerated contraction rates as compared to treated TRPC6-deficient fibroblasts. Therefore, we conclude that TRPC6 is an important determinant for TGF-β1-induced myofibroblast differentiation during fibrosis and specific channel inhibitors might be beneficial in a future treatment of PF