Anti‐inflammatory effects of melatonin in a rat model of caerulein‐induced acute pancreatitis

Abstract

The purpose of our study was to evaluate the protective effect of melatonin in a rat model of caerulein-induced acute pancreatitis. For the induction of experimental acute pancreatitis, four subcutaneous injections of caerulein (20 mgkg–1 body weight) were given to Wistar rats at 2-h intervals. Melatonin was injected intraperitoneally (25 mg kg–1 body weight) 30 min before each caerulein injection. After 12 h, rats were sacrificed by decapitation. Blood and pancreas samples were collected and processed for serological and histopathological studies,respectively. Lipase, a-amylase, corticosterone, total antioxidant power and cytokines interleukin (IL)-1b, IL-4 and tumour necrosis factor(TNF)-a were determined using commercial kits. ANOVA and Tukey tests (P<0.05) were performed for the statistical analysis of the results.Results showed that the administration of melatonin reduced histological damage induced by caerulein treatment as well as the hyperamylasemia and hyperlipidemia. Corticosterone and antioxidant total power were also reverted to basal activities. Furthermore, melatonin pre-treatment reduced pro-inflammatory cytokines IL-1b and TNF-a and increased the serum levels of anti-inflammatory cytokine IL-4. In conclusion,the findings suggest that the protective effect of melatonin in caerulein-induced acute pancreatitis is mediated by the anti-inflammatory ability of this indolamine. Thus, melatonin may have a protective effect against acute pancreatitis.

Neuropathic Pain: Delving into the Oxidative Origin and the Possible Implication of Transient Receptor Potential Channels

“…In general, scientific evidence reinforces the future use of antioxidant supplementation in several pathological conditions. Taking in account previous works of our research group (Carrasco et al, 2013 , 2014a , b ) and other authors, both preventive and therapeutic uses of antioxidants have been reported to reduce not only oxidative stress related parameters but also inflammatory response and pain in several diseases. As mentioned earlier, it has been demonstrated that current drugs used in the management of different kinds of NP are ineffective and usually not safe for the patient.…”

Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis

“…Previous experimental studies have shown that pretreatment with melatonin could prevent pancreatic inflammation and radically reduce pancreatic tissue damage in rats subjected to acute pancreatitis in different experimental models [13,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73]. This was evidenced by histological assessment of pancreatic tissue and prominent decline of the inflammatory markers, such as edema, neutrophil infiltration, and vacuolization of the acinar cells [60,61,62,63,73].…”

“…This was evidenced by histological assessment of pancreatic tissue and prominent decline of the inflammatory markers, such as edema, neutrophil infiltration, and vacuolization of the acinar cells [60,61,62,63,73]. In animals with acute pancreatitis pretreated with melatonin, there was a significant reduction in the plasma morphometric indicators of pancreatic inflammation severity, blood levels of the enzymes, amylase and lipase, and blood levels of pro-inflammatory cytokines (e.g., TNFα, IL-1β, and IL-6), whereas anti-inflammatory interleukins IL-10 and IL-4 were increased [10,59,62,63,64,65,66,67,68,69,70]. The antioxidant effect of melatonin was expressed as a reduction of lipid peroxidation products (MDA + 4-HNE) in the pancreas and was accompanied by increased activity of antioxidant enzymes SOD, CAT, GPx, and GSH [62,63,64,65,66,67,69,70].…”

“…In animals with acute pancreatitis pretreated with melatonin, there was a significant reduction in the plasma morphometric indicators of pancreatic inflammation severity, blood levels of the enzymes, amylase and lipase, and blood levels of pro-inflammatory cytokines (e.g., TNFα, IL-1β, and IL-6), whereas anti-inflammatory interleukins IL-10 and IL-4 were increased [10,59,62,63,64,65,66,67,68,69,70]. The antioxidant effect of melatonin was expressed as a reduction of lipid peroxidation products (MDA + 4-HNE) in the pancreas and was accompanied by increased activity of antioxidant enzymes SOD, CAT, GPx, and GSH [62,63,64,65,66,67,69,70]. Other mechanisms of the protective action of melatonin on acute pancreatitis involve the improvement of pancreatic blood flow, the reduction of prostaglandin generation, a decrease in myeloperoxidase (MPO), the moderation of apoptosis and necrosis processes in the pancreatic tissue, and synthesis of heat shock proteins [63,66,69,72,74].…”

Responses of Transgenic Melatonin-Enriched Goats on LPS Stimulation and the Proteogenomic Profiles of Their PBMCs

“…The rescue study by MT injection into the WT goats with LPS stimulation confirmed that the protective effects of transgenic goats on LPS were attributed to the high levels of endogenously produced MT. This is the first study to show that a high level of endogenous MT per se suppresses the toxic effects of LPS in large animals [59,60]. …”