Melatonin ameliorates the production of COX-2, iNOS, and the formation of 8-ohdg in non-targeted lung tissue after pelvic irradiation

ABSTRACT

2 [COX-2], inducible nitric oxide synthase [iNOS], and 8-hydroxydeoxyguanosine [8-OHdG] in lung tissues of Sprague-Dawley rats with and without pre-administration of melatonin. A 2x2 cm[2] area of the pelvis of male Sprague-Dawley rats with and without pre-administration of melatonin [100 mg/kg] by oral and intraperitoneal injection was irradiated with a 3 Gy dose of 1.25 MeV gamma-rays. Alterations in the levels of COX-2, iNOS, and 8-OHdG in the out-of-field lung areas of the animals were detected by enzyme immunoassay. The bystander effect significantly increased COX-2, iNOS, and 8-OHdG levels in non-targeted lung tissues [P<0.05]. Melatonin ameliorated the bystander effect of radiation and significantly reduced the level of all examined biomarkers [P<0.05]. The results indicated that the ameliorating effect of a pre-intraperitoneal [IP] injection of melatonin was noticeably greater compared to oral pre-administration. Our findings revealed that the bystander effect of radiation could induce oxidative DNA damage and increase the levels of imperative COX-2 and iNOS in non-targeted lung tissues. Interestingly, melatonin could modulate the indirect destructive effect of radiation and reduce DNA damage in non-targeted cells