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

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

Radiation-induced oxidative stress at out-of-field lung tissues after pelvis irradiation in rats

Objective: the out-of-field/non-target effect is one of the most important phenomena of ionizing radiation that leads to molecular and cellular damage to distant non-irradiated tissues. The most important concern about this phenomenon is carcinogenesis many years after radiation treatment. In vivo mechanisms and consequences of this phenomenon are not known completely. Therefore, this study aimed to evaluate the oxidative damages to out-of-field lung tissues 24 and 72 hours after pelvic irradiation in rats

Materials and Methods: in this experimental- interventional study, Sprague-Dawleymale rats [n=49] were divided into seven groups [n=7/each group], including two groups of pelvis-exposed rats [out-of-field groups], two groups of whole body- exposed rats [scatter groups], two groups of lung-exposed rats [direct irradiation groups], and one control sham group. Out-of-field groups were irradiated at a 2×2 cm area in the pelvis region with 3 Gy using 1.25 MeV cobalt-60 gamma-ray source, and subsequently, malondialdehyde [MDA] and glutathione [GSH] levels as well as superoxide dismutase [SOD] activity in out-of-field lung tissues were measured. Results were compared to direct irradiation, control and scatter groups at 24 and 72 hours after exposure. Data were analyzed using Mann-Whitney U test

Results: SOD activity decreased in out-of-field lung tissue 24 and 72 hours after irradiation as compared with the controls and scatter groups. GSH level decreased 24 hours after exposure and increased 72 hours after exposure in the out-of-field groups as compared with the scatter groups. MDA level in out-of-field groups only increased 24 hours after irradiation

Conclusion: pelvis irradiation induced oxidative damage in distant lung tissue that led to a dramatic decrease in SOD activity. This oxidative stress was remarkable, but it was less durable as compared to direct irradiation