Combination effect of melatonin and dexamethasone on liver ischemia/reperfusion injury

Abstract

OBJECTIVE: Liver failure following ischemia-reperfusion (I/R) injury is a major concern in liver surgery. The purpose of this study was to evaluate combination pretreatment with melatonin (MEL) and dexamethasone (DEX) on liver I/R model. Male Wistar rats (n = 60) were assigned to 5 groups of 12 animals each: (1) Sham: laparotomy without I/R; (2) I/R: hepatic I/R; (3) I/R+MEL: hepatic I/R+melatonin injected intraperitoneally (20 mg/kg); (4) I/ R+DEX: hepatic I/R+ dexamethasone injected intravenously (10 mg/kg); (5) I/R+MEL+DEX: hepatic I/R+ melatonin injected intraperitoneally+dexamethasone injected intravenously. The liver was subjected to ischemia by clamping the portal triad for 30 minutes and then reperfused for 6 hours after ischemia by removing the clamps. RESULTS: The levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) decreased after hepatic I/R in all groups. Levels of GPx and SOD were higher in I/R+MEL+DEX group compared to I/R, I/R+MEL and I/ R+DEX groups and they were signifi cantly higher in I/R+MEL group compared to I/R and I/R+DEX groups (p < 0.05). Levels of ALT, AST, TNF-α, hepatic tissue malondialdehyde (MDA), liver injury index, and apoptotic index increased after hepatic I/R. Levels of ALT, AST, tissue MDA, tissue injury index and apoptotic index were lower in I/R+MEL+DEX group compared to those in I/R, I/R+MEL and I/R+DEX groups, and in I/R+MEL they were signifi cantly lower than in I/R+DEX group (p < 0.05). TNF-α level was lower in I/R+MEL+DEX group compared to other groups and it was signifi cantly lower in I/R+DEX group than in I/R+MEL and I/R groups (p < 0.05). CONCLUSION: Combination therapy with melatonin and dexamethasone had better results in decreasing the liver injury compared to when each of them was administered alone (Tab.

Effect of dexamethasone on the endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) genes expression during hepatic warm ischemia/reperfusion in rat

“…Greenwald et al found that neutrophils destroyed the hyaluronic acid of synovial fluid by producing ROS (30). Taghizadieh et al also showed that dexamethasone reduced the production of MDA and maintained the level of the antioxidant enzyme in liver during I/R (31). Dexamethasone ameliorates MDA, so it indirectly exerts an antioxidative effect, which can be confirmed by our results.…”

“…Glucocorticoids can limit the inflammatory damage to the glycocalyx by suppressing the production of cytokines and chemokines and also through preventing the infiltration of inflammatory cells into tissues and mast cell degranulation. In a sample of isolated heart, hydrocortisone was able to significantly inhibit destruction of the endothelial surface layer after ischemia and during reperfusion and reduce TNF-α induction (31). In this study, we demonstrated that dexamethasone reduced parenchymal cell injury (reduction of ALT and AST) and also significantly ameliorated the glycocalyx damage in the group DEX + IR.…”

Extracellular vesicles from endothelial progenitor cells prevent steroid-induced osteoporosis by suppressing the ferroptotic pathway in mouse osteoblasts based on bioinformatics evidence

“…The difference in the doses of glucocorticoids may affect the expression of GPX1, GPX4, MnSOD, SOD1, SOD2 and other antioxidants in pregnant animals at different time points 45 . In addition, high-dose glucocorticoids can also reduce the expression of SOD and GPX in cells such as macrophages and skeletal muscle 46 . Clinical trials have confirmed that patients with long-term hormone therapy, postmenopausal therapy, and primary osteoporosis have low levels of GPX and SOD 47 .…”

Effects of Melatonin on Liver Injuries and Diseases

“…Liver failure subsequent ischemia-reperfusion (I/R) injury is recognized as a main difficulty in liver surgery [ 91 ]. Melatonin is a powerful endogenous antioxidant that possesses a protective role in liver I/R injury [ 92 , 93 ].…”