Neurotropin demonstrates cytoprotective effects in lung cells t

Neurotropin, a non-protein extract from inflamed rabbit skin inoculated with vaccinia virus, is well-known as an analgesic drug, but its cytoprotective effects have not been explored. Since infection by viruses such as human T-cell leukemia virus type-I and Epstein Barr induces expression of the redox-regulating molecule thioredoxin (TRX), we hypothesized that Neurotropin would also be capable of regulating the redox balance and could be applied for the therapeutics of lung diseases caused by oxidative stress such as chronic obstructive pulmonary disease (COPD). Neurotropin enhanced mRNA expression of the redox-regulating molecules glutathione peroxidase (GPX) and catalase (CAT), and particularly TRX, in human lung adenocarcinoma A549 cells. Neurotropin also increased the cellular TRX content and regulated TRX release from cells. The cytoprotective effects of Neurotropin against hydrogen peroxide and cigarette smoke extracts was demonstrated by an attenuation of lactate dehydrogenase (LDH) release from oxidant-exposed A549 cells and the inhibition of apoptosis. This cytoprotection was linked with reduced activity of intracellular oxidants. Furthermore, Neurotropin enhanced TRX expression in mouse lungs and ameliorated cigarette smoke-induced lung injury in mice, suggesting its cytoprotective effects in lung epithelial cells are mediated through the induction of redox-regulating molecules that reduce intracellular oxidative activity.