Depertment of Physiology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, Türkiye.
Department of Physiology, Faculty of Medicine, Sakarya University, Sakarya 54100, Türkiye.
Life Sci. 2023 Sep 15;329:121875. doi: 10.1016/j.lfs.2023.121875. Epub 2023 Jun 22.
To investigate the combined therapeutic potential of melatonin and ascorbic acid in mitigating sepsis-induced heart and kidney injury in male rats and assess the combination therapy's effects on inflammation, cellular damage, oxidative stress, and vascular function-related markers.
Cecal ligation and puncture (CLP) induced sepsis in male rats, which were divided into five groups: Sham, CLP, MEL (melatonin), ASA (ascorbic acid), and MEL+ASA (melatonin and ascorbic acid). Rats were treated, and heart and kidney tissues were collected for biochemical and histopathological analyses. Inflammatory markers (presepsin, procalcitonin, NF-κB, IL-1β, IL-6, TNF-α), cellular damage marker (8-OHDG), oxidative status, nitric oxide (NO), vascular endothelial growth factor (VEGF), and sirtuin 1 (SIRT1) levels were assessed.
Melatonin and ascorbic acid treatment reduced inflammatory and cellular damage markers compared to the CLP group. Combined treatment improved NO, VEGF levels, and increased SIRT1 expression, suggesting a synergistic effect in mitigating sepsis-induced inflammation, cellular damage, and oxidative stress. Histopathological analyses supported these findings, revealing reduced heart and kidney injury in the MEL+ASA group.
Our study highlights potential benefits of combining melatonin and ascorbic acid as a therapeutic strategy for alleviating sepsis-induced heart and kidney injury. The synergistic effects of these agents may provide stronger protection against inflammation, oxidative stress, and tissue damage, opening new avenues for future research and clinical applications in sepsis management.
研究褪黑素和抗坏血酸联合治疗对雄性大鼠脓毒症诱导的心肾损伤的潜在治疗作用,并评估联合治疗对炎症、细胞损伤、氧化应激和血管功能相关标志物的影响。
采用盲肠结扎穿孔(CLP)法诱导雄性大鼠脓毒症,将其分为五组:假手术(Sham)组、CLP 组、MEL(褪黑素)组、ASA(抗坏血酸)组和 MEL+ASA(褪黑素和抗坏血酸)组。对大鼠进行治疗,并收集心脏和肾脏组织进行生化和组织病理学分析。评估炎症标志物(降钙素原前肽、降钙素原、核因子-κB、白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α)、细胞损伤标志物(8-羟基脱氧鸟苷)、氧化状态、一氧化氮(NO)、血管内皮生长因子(VEGF)和沉默信息调节因子 1(SIRT1)水平。
与 CLP 组相比,褪黑素和抗坏血酸治疗降低了炎症和细胞损伤标志物。联合治疗可改善 NO、VEGF 水平,增加 SIRT1 表达,提示在减轻脓毒症诱导的炎症、细胞损伤和氧化应激方面具有协同作用。组织病理学分析支持了这些发现,表明 MEL+ASA 组的心肾损伤减轻。
本研究强调了褪黑素和抗坏血酸联合治疗作为减轻脓毒症诱导的心肾损伤的潜在治疗策略的重要性。这些药物的协同作用可能为炎症、氧化应激和组织损伤提供更强的保护,为脓毒症管理的未来研究和临床应用开辟了新的途径。