The protective role of melatonin on L-arginine-induced acute pancreatitis in adult male albino rats

Sadek, Ahmed Fathy; Khattab, Rehab

doi:10.5603/fm.a2016.0029

Cited by 9 publications

(9 citation statements)

References 35 publications

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“…2017). Melatonin protects against Arg-induced AP in adult male Albino rats (Sadek and Khattab 2017). Inhibition of arginase activity ameliorated Arg-induced AP in Wistar rats (Biczó et al.…”

Section: Discussionmentioning

confidence: 99%

Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling

Zhang

Zang

et al. 2019

Pharmaceutical Biology

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Context: Oxymatrine (OMT) has various pharmacological effects, including immune reaction regulation, anti-inflammation and anti-hypersensitive reaction.Objective: This is the first report to investigate the molecular mechanism of OMT function in l-arginine (Arg)-induced acute pancreatitis (AP) involving intestinal injury.Materials and methods: Rat pancreatic AR42J and small intestinal IEC-6 cells were treated with Arg (200–800 µM) for 48 h plus OMT (4 mg/mL) treatment. Thirty adult Wistar rats were randomly assigned to control (saline), AP (i.p. of 250 mg/100 g body weight Arg) and OMT (i.p. injection of 50 mg/kg b.w. OMT every 6 h following Arg). Both cells and rats were harvested at 48 h.Results: Arg-induced cell proliferation in both rats AR42J (EC50 633.9 ± 31.4 µM) and IEC-6 cells (EC50 571.3 ± 40.4 µM) in a dose-dependent manner, which was significantly inhibited by OMT (4 mg/mL). Meanwhile, Arg (600 µM) induced expression of proinflammatory cytokines (TNF-α, IL-6, IL-1β, NF-κB, IL-17A/IL-17F and IFN-γ) and activation of p-p38/p-ERK in vitro, which was reversed by OMT. In vivo, OMT (50 mg/kg) inhibited 250 mg/100 g of Arg-induced AP involving intestinal injury, including inhibiting Arg-induced inflammatory in pancreas and intestine, inhibiting Arg-induced increase of TNF-α, IL-6, IL-1β, NF-κB and p-p38/p-ERK-MAPK signalling, and inhibiting Arg-induced increase of IL-17A/IL-17F, IFN-γ, ROR-γt and T-bet. Meanwhile, OMT inhibited Arg-induced expression of CD44 and CD55 in intestinal injury.Discussion and conclusions: OMT protects against Arg-induced AP involving intestinal injury via regulating Th1/Th17 cytokines and MAPK/NF-κB signalling, which is a promising therapeutic agent in clinics.

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Section: Discussionmentioning

confidence: 99%

Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling

Zhang

Zang

et al. 2019

Pharmaceutical Biology

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“…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].…”

Section: Melatonin System and Acute Pancreatitismentioning

confidence: 99%

“…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].…”

Section: Melatonin System and Acute Pancreatitismentioning

confidence: 99%

“…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].…”

Section: Melatonin System and Acute Pancreatitismentioning

confidence: 99%

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

Jaworek

Leja-Szpak

Nawrot-Porąbka

et al. 2017

IJMS

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Melatonin is an indoleamine produced from the amino acid l-tryptophan, whereas metabolites of melatonin are known as kynuramines. One of the best-known kynuramines is N1-acetyl-N1-formyl-5-methoxykynuramine (AFMK). Melatonin has attracted scientific attention as a potent antioxidant and protector of tissue against oxidative stress. l-Tryptophan and kynuramines share common beneficial features with melatonin. Melatonin was originally discovered as a pineal product, has been detected in the gastrointestinal tract, and its receptors have been identified in the pancreas. The role of melatonin in the pancreatic gland is not explained, however several arguments support the opinion that melatonin is probably implicated in the physiology and pathophysiology of the pancreas. (1) Melatonin stimulates pancreatic enzyme secretion through the activation of entero-pancreatic reflex and cholecystokinin (CCK) release. l-Tryptophan and AFMK are less effective than melatonin in the stimulation of pancreatic exocrine function; (2) Melatonin is a successful pancreatic protector, which prevents the pancreas from developing of acute pancreatitis and reduces pancreatic damage. This effect is related to its direct and indirect antioxidant action, to the strengthening of immune defense, and to the modulation of apoptosis. Like melatonin, its precursor and AFMK are able to mimic its protective effect, and it is commonly accepted that all these substances create an antioxidant cascade to intensify the pancreatic protection and acinar cells viability; (3) In pancreatic cancer cells, melatonin and AFMK activated a signal transduction pathway for apoptosis and stimulated heat shock proteins. The role of melatonin and AFMK in pancreatic tumorigenesis remains to be elucidated.

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“…They were after arrival from the supplier left for two weeks for acclimatization. Rats were fed a standard diet of commercial rat chow and tap water ad libitum through the time of the study (Sadek and Khattab 2017). The animal care and experiments protocol described in this study were complied with "Research Ethics Committee" Faculty of Medicine, Minia University, Egypt, which are in accordance with the NIH Guide for Care and Use of Laboratory Animals (U.S. Department of Health and Human Services, NIH 1992).…”

Section: Methodsmentioning

confidence: 99%

Comparing the preventive effect of sodium hydrosulfide, leptin, and curcumin against L-arginine induced acute pancreatitis in rats: role of corticosterone and inducible nitric oxide synthase

Ragy

Ali

Toni

2019

Endocrine Regulations

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Objectives. Acute pancreatitis (AP) is a life-threatening condition. Using antioxidants in AP is insufficient and conflicting. Therefore, this study compared the effect of hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS), leptin or curcumin pretreatment on AP induced by L-arginine.Methods. Forty adult male rats were used and classified into: 1) control; 2) AP group [each rat was intraperitoneally (i.p.) injected with 2 doses of L-arginine of 250 mg/100 g body weight (b.w.) with an interval of 1 h]; 3) NaHS+AP group (each rat was i.p. injected with 10 mg/kg b.w. of NaHS 1 h before induction of AP); 4) leptin+AP group (each rat was pretreated with 10 μg/kg b.w. of leptin 30 min before induction of AP; and 5) curcumin+AP group (in which rats were i.p. injected with 150 mg/kg b.w. of curcumin 30 min before induction of AP). Serum amylase, lipase, nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and corticosterone (CORT) levels were assayed. In addition, pancreatic tissues were obtained for histopathological examination and malondialde-hyde (MDA), total antioxidant capacity (TAC), and inducible nitric oxide synthase (iNOS) levels were measured.Results. All AP treated groups showed significant decrease in serum levels of pancreatic enzymes, NO, and TNF-α, and pancreatic MDA and iNOS levels, while TAC levels were significantly increased. NaHS caused more limitation of inflammation than leptin and curcumin by affecting iNOS. Leptin was more potent than curcumin due to the stimulatory effect of leptin on glucocorticoid release to counteract inflammation.Conclusions. NaHS was more effective in AP amelioration than the leptin and curcumin.

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The protective role of melatonin on L-arginine-induced acute pancreatitis in adult male albino rats

Cited by 9 publications

References 35 publications

Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling

Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling

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

Comparing the preventive effect of sodium hydrosulfide, leptin, and curcumin against L-arginine induced acute pancreatitis in rats: role of corticosterone and inducible nitric oxide synthase

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