Protective effect of melatonin and ascorbic acid combination on sepsis‐induced lung injury: An Experimental study

• Published in: Clinical and experimental pharmacology & physiology Vol. 50; no. 8; pp. 634 - 646
• Main Authors: Üstündağ, Hilal, Demir, Özlem, Çiçek, Betül, Huyut, Mehmet Tahir, Yüce, Neslihan, Tavacı, Taha
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01-08-2023
• Subjects: Animal tissues; Animals; antioxidant; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Arylesterase; Ascorbic acid; Ascorbic Acid - pharmacology; Ascorbic Acid - therapeutic use; Caspase-3; Catalase; Cecum; Edema; Glutathione; Glutathione - metabolism; Glutathione peroxidase; Histopathology; Inflammation; Inflammation - pathology; Injury prevention; Interleukins; Lung; lung injury; Lung Injury - drug therapy; Lung Injury - etiology; Lung Injury - prevention & control; Lungs; Lymphocytes; Melatonin; Melatonin - pharmacology; Melatonin - therapeutic use; Metastases; Oxidants; Oxidation; Oxidative Stress; Oxidizing agents; Paraoxonase; Peroxidase; Rats; Sepsis; Sepsis - complications; Sepsis - drug therapy; Superoxide dismutase; Tumor necrosis factor; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-TNF; antioxidant; ascorbic acid; lung injury; inflammation; caspase 3; melatonin; oxidative stress; sepsis
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.13780

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.