Microwave (MW) radiation poses the risk of potential hazards on human health. The present study investigated the effects of MW 10 GHz exposure for 3 h/day for 30 days at power densities of 5.23 ± 0.25 and 10.01 ± 0.15 mW/cm2 in the skin of rats. The animals exposed to 10 mW/cm2 (corresponded to twice the ICNIRP-2020 occupational reference level of MW exposure for humans) exhibited significant biophysical, biochemical, molecular and histological alterations compared to sham-irradiated animals. Infrared thermography revealed an increase in average skin surface temperature by 1.8°C and standard deviation of 0.3°C after 30 days of 10 mW/cm2 MW exposure compared to the sham-irradiated animals. MW exposure also led to oxidative stress (ROS, 4-HNE, LPO, AOPP), inflammatory responses (NFkB, iNOS/NOS2, COX-2) and metabolic alterations [hexokinase (HK), lactate dehydrogenase (LDH), citrate synthase (CS) and glucose-6-phospahte dehydrogenase (G6PD)] in 10 mW/cm2 irradiated rat skin. A significant alteration in expression of markers associated with cell survival (Akt/PKB) and HSP27/p38MAPK-related stress-response signaling cascade was observed in 10 mW/cm2 irradiated rat skin compared to sham-irradiated rat skin. However, MW-irradiated groups did not show apoptosis, evident by unchanged caspase-3 levels. Histopathological analysis revealed a mild cytoarchitectural alteration in epidermal layer and slight aggregation of leukocytes in 10 mW/cm2 irradiated rat skin. Altogether, the present findings demonstrated that 10 GHz exposure in continuous-wave mode at 10 mW/cm2 (3 h/day, 30 days) led to significant alterations in molecular markers associated with adaptive stress-response in rat skin. Furthermore, systematic scientific studies on more prevalent pulsed-mode of MW-radiation exposure for prolonged duration are warranted.

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