No abstract

:  Melatonin exhibits a wide variety of biological effects, including antioxidant and anti‐inflammatory functions. Its antioxidant role impedes the etiopathogenesis of pancreatitis, but little is known about the signaling pathway of melatonin in the induction of antioxidant enzymes in acute pancreatitis (AP). The aim of this study was to determine whether melatonin could prevent cerulein‐induced AP through nuclear factor erythroid 2‐related factor 2 (Nrf2) and curtail inflammation by inhibition of NF‐κB. AP was induced by two intraperitoneal (i.p.) injections of cerulein at 2 h intervals (50 μg/kg) in Sprague‐Dawley rats. Melatonin (10 or 50 mg/kg/daily, i.p.) was administered 24 h before each injection of cerulein. The rats were killed 12 h after the last injection. Acinar cell degeneration, pancreatic edema, and inflammatory infiltration were significantly different in cerulein‐ and melatonin‐treated rats. Melatonin significantly reduced amylase, lipase, MPO, and MDA levels, and increased antioxidant enzyme activities including SOD and GPx, which were decreased in AP (P < 0.05). Melatonin increased the expression of NQO1, HO‐1, and SOD2 when compared with the cerulein‐induced AP group (P < 0.05). In addition, melatonin increased Nrf2 expression, and reduced expressions of tumor necrosis factor‐alpha, IL‐1β, IL‐6, IL‐8, and iNOS. The elevated nuclear binding of NF‐κB in the cerulein‐induced pancreatitis group was inhibited by melatonin. These results show that melatonin increases antioxidant enzymes and Nrf2 expression, and limits inflammatory mediators in cerulein‐induced AP. It is proposed that melatonin may play an important role in oxidative stress via the Nrf2 pathway in parallel with reduction of inflammation by NF‐κB inhibition.

Melatonin has potent hepatoprotective effects as an antioxidant. However, the signaling pathway of melatonin in the induction of antioxidant enzymes against acute liver injury is not fully understood. The study aimed to determine whether melatonin could prevent dimethylnitrosamine (DMN)-induced liver injury through nuclear erythroid 2-related factor 2 (Nrf2) and inflammation. Liver injury was induced in rats by a single injection of DMN (30 mg/kg, i.p.). Melatonin treatment (50 mg/kg/daily, i.p.) was initiated 24 hr after DMN injection for 14 days, after which the rats were killed and samples were collected. Serum and antioxidant enzyme activities improved in melatonin-treated rats, compared with DMN-induced liver injury group (P < 0.01). Melatonin reduced the infiltration of inflammatory cells and necrosis in the liver, and increased the expression of NADPH: quinone oxidoreductase-1, heme oxygenase-1, and superoxide dismutase-2, which were decreased by DMN. Melatonin increased expression of novel transcription factor, Nrf2, and decreased expression of inflammatory mediators including tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and inducible nitric oxide synthase. The increased nuclear binding of nuclear factor-kappa B (NF-kappaB) in the DMN-induced liver injury group was inhibited by melatonin. Our results show that melatonin increases antioxidant enzymes and Nrf2 expression in parallel with the decrease of inflammatory mediators in DMN-induced liver injury, suggesting that melatonin may play a role of antioxidant defense via the Nrf2 pathway, by reducing inflammation by NF-kappaB inhibition.

No abstract

Oxidative stress in liver injury is a major pathogenetic factor in progress of liver fibrosis. Resveratrol, a representative antioxidant derived from grapes, has been reported to show widespread pharmacological properties. In this study, we investigated the protective effects of resveratrol on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Rats were treated with resveratrol daily by oral gavage for seven days after a single intraperitoneal injection of DMN (40 mg/kg). Resveratrol remarkably recovered body and liver weight loss due to DMN-induced liver fibrosis. Liver histology showed that resveratrol alleviated the infiltration of inflammatory cells and fibrosis of liver tissue. Resveratrol decreased the level of malondialdehyde and increased the levels of glutathione peroxidase and superoxide dismutase. Also, resveratrol significantly inhibited the mRNA expression of inflammatory mediators including inducible nitric oxide, tumor necrosis factor-alpha and interleukin-1beta. In addition, resveratrol showed not only reduced mRNA expression of fibrosis-related genes such as transforming growth factor beta 1, collagen type I, and alpha-smooth muscle actin, but also a significant decrease of hydroxyproline in rats with DMN-induced liver fibrosis. Our results suggest that resveratrol could be used to treat liver injury and fibrosis and be useful in preventing the development of liver fibrosis and cirrhosis.

No abstract

The 6-year cumulative HCC development rate was 6.5% in CHB patients treated with entecavir or tenofovir. Age ≥50 years and liver cirrhosis were found to predict HCC development in these patients.

The purpose of this study was to investigate possible beneficial effects of morin on CCl(4)-induced acute hepatotoxicity in rats. Rats received a single dose of CCl(4) (150 microL/100 g 1:1 in corn oil). Morin treatment (20 mg/kg) was given at 48, 24, and 2 h before CCl(4) administration. CCl(4) challenge elevated serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) levels, but these effects were prevented by the pretreatment of rats with morin. To identify the mechanism of protective activity of morin in CCl(4)-induced hepatotoxicity in rats, we investigated expressions of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and inducible nitric oxide (iNOS). The expressions of TNF-alpha, IL-1beta, IL-6, and iNOS were increased by CCl(4) treatment and increased expressions of those were decreased by morin. These findings suggest that morin prevents acute liver damage by inhibiting the production of TNF-alpha, IL-1beta, IL-6, and iNOS.