Department of Physiology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey.
Department of Histology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey.
Clin Exp Pharmacol Physiol. 2023 Aug;50(8):634-646. doi: 10.1111/1440-1681.13780. Epub 2023 May 18.
This study investigated the synergistic protective effects of melatonin (MEL) and ascorbic acid (vitamin C, ASA) in treating sepsis-induced lung injury in rats. Rats were divided into five groups: control, cecal ligation and puncture (CLP), CLP + MEL, CLP + ASA and CLP + MEL + ASA. The effects of MEL (10 mg/kg), ASA (100 mg/kg) and their combination on oxidative stress, inflammation and histopathology were evaluated in septic rats' lung tissues. Sepsis-induced oxidative stress and inflammation were evident through increased levels of malondialdehyde (MDA), myeloperoxidase (MPO), total oxidant status (TOS) and oxidative stress index (OSI); decreased levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx); and elevated levels of tumour necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) in the lung tissue. Treatment with MEL, ASA and their combination significantly improved antioxidant capacity and reduced oxidative stress, with the combination treatment being more effective. The combination treatment also significantly reduced TNF-α and IL-1β levels and improved peroxisome proliferator-activated receptor (PPAR), arylesterase (ARE) and paraoxonase (PON) levels in the lung tissue. Histopathological examination showed reduced oedema and lymphocyte infiltration with a lung tissue appearance similar to the control group. Immunohistochemical staining for caspase 3 demonstrated reduced immune positivity in the treatment groups. In conclusion, this study supports the potential synergistic protective effects of MEL and ASA in treating sepsis-induced lung injury. The combination therapy could effectively reduce oxidative stress, inflammation and improve antioxidant capacity in septic rats, suggesting a promising strategy for treating sepsis-induced lung injury.
本研究探讨了褪黑素(MEL)和抗坏血酸(维生素 C,ASA)联合治疗大鼠脓毒症性肺损伤的协同保护作用。大鼠分为五组:对照组、盲肠结扎穿孔(CLP)组、CLP+MEL 组、CLP+ASA 组和 CLP+MEL+ASA 组。评估 MEL(10mg/kg)、ASA(100mg/kg)及其联合用药对脓毒症大鼠肺组织氧化应激、炎症和组织病理学的影响。脓毒症诱导的氧化应激和炎症通过增加丙二醛(MDA)、髓过氧化物酶(MPO)、总氧化剂状态(TOS)和氧化应激指数(OSI)水平;降低超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)水平;以及肺组织中肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平来证实。MEL、ASA 及其联合治疗可显著改善抗氧化能力,降低氧化应激,联合治疗效果更为显著。联合治疗还可显著降低 TNF-α和 IL-1β水平,提高肺组织过氧化物酶体增殖物激活受体(PPAR)、芳基酯酶(ARE)和对氧磷酶(PON)水平。组织病理学检查显示水肿和淋巴细胞浸润减少,肺组织外观与对照组相似。免疫组织化学染色 Caspase 3 显示治疗组免疫阳性减少。综上所述,本研究支持 MEL 和 ASA 联合治疗脓毒症性肺损伤的潜在协同保护作用。联合治疗可有效降低脓毒症大鼠的氧化应激、炎症和提高抗氧化能力,为脓毒症性肺损伤的治疗提供了一种有前途的策略。