Comparative analysis of melatonin's protective role against flattening filter and flattening filter-free X-ray induced nephropathy: focus on apoptosis and SIRT1 modulation.

BACKGROUND: Radiation-induced nephropathy is a major concern, particularly for patients undergoing radiotherapy. This study investigates melatonin's (MEL) protective effects against kidney damage induced by Flattening Filter (low dose rate-LDR) and Flattening Filter Free (high dose rate-HDR) X-ray by focusing on apoptosis and SIRT1 modulation in rats. METHODS: Forty rats were divided into five groups (n = 8): Group 1 (control), Group 2 (FF-LDR, 400MU/min), Group 3 (MEL + FF-LDR), Group 4 (FFF-HDR, 1400MU/min), and Group 5 (MEL + FFF-HDR). Groups 3 and 5 received 10 mg/kg MEL intraperitoneally 15 min before an 8 Gy abdominal irradiation. Rats were sacrificed 48 h post-radiotherapy for histopathological and immunohistochemical analyses of the kidney. RESULTS: The FFF-HDR group showed fewer atypical glomeruli and lost brush borders, and epithelial connections compared to the FF-LDR group. The MEL + FFF-HDR group had significantly fewer atypical glomeruli and brush border losses than the MEL + FF-LDR group. Additionally, while SIRT1 expression increased in both the FF and FFF groups following MEL treatment, this increase was significant only in the MEL + FFF-HDR group compared to the control group. MEL pretreatment effectively decreased cellular apoptosis in both MEL + FFF-HDR and MEL + FF-LDR groups. CONCLUSIONS: Melatonin has been proven to be an effective radioprotective agent against renal nephropathy and cellular apoptosis induced by FF and FFF beams. Additionally, pre-treatment with MEL has been shown to enhance SIRT1 expression, thereby protecting the kidneys from acute radiation damage, particularly from high-dose rate radiation.