Nrf2 and NF‐қB interplay in tamoxifen‐induced hepatic toxicity: A promising therapeutic approach of sildenafil and low‐dose γ radiation

Tamoxifen-induced hepatotoxicity is an inevitable side effect during breast cancer treatment. Low-dose gamma irradiation (IRR) shows many beneficial effects by stimulating various biological processes. This study evaluates the possible effect of sildenafil and low-dose gamma radiation on liver damages as new treatment strategies. Group I (control), group II: (tamoxifen), group III: (tamoxifen + Sildenafil), group IV: (tamoxifen+ irradiation) and group V: (tamoxifen +Sildenafil + irradiation). Rats were sacrificed after 5 h from tamoxifen injection. Results showed that tamoxifen caused elevation in serum AST, ALT and ALP as well hepatic ROS, iNOS, MDA, Keap-1 and NF-Kb, in addition to diminution in hepatic Nrf2 and HO-1. Exposure to low-dose gamma radiation and sildenafil amended the alterations in the measured parameters in serum and tissue. Moreover, all results were confirmed by histopathological examination. In conclusion, sildenafil and low-dose gamma radiation can mitigate the toxicity induced by tamoxifen in liver tissues. Hence, this treatment could be further evaluated as a new approach for alleviating various liver disorders.