Bee honey and Nigella sativa inhibit nitric oxide mediated cytochrome C release and down regulation of connexin 43 induced by methylnitrosourea in hepatic tissues of Sprague Dawley rats

ABSTRACT

We investigated the protective effect of bee honey and Nigella sativa against methylnitrosourea [MNU] induced oxidative stress, apoptosis and down-regulation of the gap junction protein connexin 43 [Cx43] in hepatic tissues. Our results showed that MNU induced hepatic dysplasia and oxidative stress through decreasing reduced glutathione [GSH] level, decreasing the activities of glutathione reductase [GRase] and superoxide dismutase [SOD], enhancing glutathione peroxidase [GPx] activity and elevating nitric oxide [NO] level in liver tissues as compared to control. Apoptosis, as indicated by significant release of cytochrome c [cyto c] from mitochondria into the cytosol, was observed in MNU injected rats and was positively correlated with the elevation of N0 level. Bee honey and Nigella protected against the previous deleterious changes by significant elevation of GSH level, increasing the activities of GRase and SOD, decreasing the activity of GPx, decreasing NO level and stopping release of cyto c from mitochondria as compared to MNU injected rats. Moreover, down-regulation of Cx43 by MNU was prevented in 50% and 75% of animals that received Nigella alone or both Nigella and bee honey, respectively. These data illustrated the consequences of MNU induced hepatocellular dysplastic changes and oxidative stress and shed the light about the possible sites targeted by bee honey and Nigella in their protective effect against the earlier stages of liver carcinogenesis