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

被引:12
作者
Ustundag, Hilal [1 ]
Demir, Ozlem [2 ]
Cicek, Betul [1 ]
Huyut, Mehmet Tahir [3 ]
Yuce, Neslihan [4 ]
Tavaci, Taha [5 ]
机构
[1] Erzincan Binali Yildirim Univ, Fac Med, Dept Physiol, Erzincan, Turkiye
[2] Erzincan Binali Yildirim Univ, Fac Med, Dept Histol, Erzincan, Turkiye
[3] Erzincan Binali Yildirim Univ, Fac Med, Dept Biostat, Erzincan, Turkiye
[4] Ataturk Univ, Fac Med, Dept Biochem, Erzurum, Turkiye
[5] Ataturk Univ, Fac Med, Dept Pharmacol, Erzurum, Turkiye
关键词
antioxidant; ascorbic acid; caspase; 3; inflammation; lung injury; melatonin; oxidative stress; sepsis; OXIDATIVE STRESS; RAT MODEL; VITAMIN-C; INFLAMMATION; EXPRESSION; DAMAGE; DYSFUNCTION;
D O I
10.1111/1440-1681.13780
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) 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-alpha and IL-1 beta 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.
引用
收藏
页码:634 / 646
页数:13
相关论文
共 54 条
[1]   Oxidant stress in kidneys of spontaneously hypertensive rats involves both oxidase overexpression and loss of extracellular superoxide dismutase [J].
Adler, S ;
Huang, H .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2004, 287 (05) :F907-F913
[2]   Age dependent expression of melatonin membrane receptor (MT1, MT2) and its role in regulation of nitrosative stress in tropical rodent Funambulus pennanti [J].
Ahmad, Raise ;
Gupta, Sameer ;
Haldar, Chandana .
FREE RADICAL RESEARCH, 2012, 46 (02) :194-203
[3]   (1 → 3)-β-d-glucan enhances the toxicity induced by Bortezomib in rat testis [J].
Akaras, Nurhan ;
Abuc, Ozlem Ozgul ;
Koc, Kubra ;
Bal, Tugba ;
Geyikoglu, Fatime ;
Atilay, Hilal ;
Erol, Huseyin Serkan ;
Yigit, Serdar ;
Gul, Murat .
JOURNAL OF FOOD BIOCHEMISTRY, 2020, 44 (03)
[4]   Melatonin suppresses markers of inflammation and oxidative damage in a human daytime endotoxemia model [J].
Alamili, Mahdi ;
Bendtzen, Klaus ;
Lykkesfeldt, Jens ;
Rosenberg, Jacob ;
Gogenur, Ismail .
JOURNAL OF CRITICAL CARE, 2014, 29 (01) :184.e9-184.e13
[5]   Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat [J].
Armour, J ;
Tyml, K ;
Lidington, D ;
Wilson, JX .
JOURNAL OF APPLIED PHYSIOLOGY, 2001, 90 (03) :795-803
[6]   Melatonin pretreatment modulates anti-inflammatory, antioxidant, YKL-40, and matrix metalloproteinases in endotoxemic rat lung tissue [J].
Ates, Gulten ;
Tamer, Sule ;
Yorulmaz, Hatice ;
Mutlu, Sevcihan ;
Olgac, Vakur ;
Aksu, Abdullah ;
Caglar, Nuray Balkis ;
Ozkok, Elif .
EXPERIMENTAL BIOLOGY AND MEDICINE, 2022, 247 (12) :1080-1089
[7]   Melatonin for the treatment of sepsis: the scientific rationale [J].
Biancatelli, Ruben Manuel Luciano Colunga ;
Berrill, Max ;
Mohammed, Yassen H. ;
Marik, Paul E. .
JOURNAL OF THORACIC DISEASE, 2020, 12 :S54-S65
[8]   MEASUREMENT OF CUTANEOUS INFLAMMATION - ESTIMATION OF NEUTROPHIL CONTENT WITH AN ENZYME MARKER [J].
BRADLEY, PP ;
PRIEBAT, DA ;
CHRISTENSEN, RD ;
ROTHSTEIN, G .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1982, 78 (03) :206-209
[9]   Hyaluronic acid and chondroitin-4-sulphate treatment reduces damage in carbon tetrachloride-induced acute rat liver injury [J].
Campo, GM ;
Avenoso, A ;
Campo, S ;
Ferlazzo, AM ;
Micali, C ;
Zanghì, L ;
Calatroni, A .
LIFE SCIENCES, 2004, 74 (10) :1289-1305
[10]   Sepsis and septic shock [J].
Cecconi, Maurizio ;
Evans, Laura ;
Levy, Mitchell ;
Rhodes, Andrew .
LANCET, 2018, 392 (10141) :75-87