Melatonin attenuates lipopolysaccharide (LPS)-induced apoptotic liver damage in d-galactosamine-sensitized mice

Wang, Hua; D, Xu; Lv, Jin-Wei; Ning, Huan; Wei, Wei

doi:10.1016/j.tox.2007.04.021

Cited by 79 publications

(68 citation statements)

References 52 publications

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“…It was reported that melatonin can reduce free radical damage by elevating GPx activation [11,39] . Montilla et al [25] reported that acute ligation of the bile duct is accompanied with decreased GSH levels both in plasma and in liver, as well as significantly reduced antioxidant enzyme activities.…”

Section: Discussionmentioning

confidence: 99%

Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats

Ren¹,

Xu²,

Qiao³

2009

WJG

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AIM:To investigate the protective effects of melatonin on carbon tetrachloride (CCl 4 )-induced hepatic fibrosis in experimental rats. METHODS:All rats were randomly divided into normal control group, model control group treated with CCl 4 for 12 wk, CCl 4 + NAC group treated with CCl 4 + NAC (100 mg/kg, i.p.) for 12 wk, CCl 4 + MEL-1 group treated with CCl 4 + melatonin (2.5 mg/kg) for 12 wk, CCl 4 + MEL-2 group treated with CCl 4 + melatonin (5.0 mg/kg) for 12 wk, and CCl 4 + MEL-3 group treated with CCl 4 + melatonin (10 mg/kg). Rats in the treatment groups were injected subcutaneously with sterile CCl 4 (3 mL/kg, body weight) in a ratio of 2:3 with olive oil twice a week. Rats in normal control group received hypodermic injection of olive oil at the same dose and frequency as those in treatment groups. At the end of experiment, rats in each group were anesthetized and sacrificed. Hematoxylin and eosin (HE) staining and Van Gieson staining were used to examine changes in liver pathology. Serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and protein concentration were measured with routine laboratory methods using an autoanalyzer. Hydroxyproline (HYP) content in liver and malondialdehyde (MDA) and glutathione peroxidase (GPx) levels in liver homogenates were assayed by spectrophotometry. Serum hyaluronic acid (HA), laminin (LN), and procollagen Ⅲ N-terminal peptide (PⅢNP) were determined by radioimmunoassay. RESULTS:Pathologic grading showed that the fibrogenesis was much less severe in CCl 4 + MEL3 group than in model control group (u = 2.172, Moreover, treatment with melatonin (5, 10 mg/kg) significantly reduced the MDA content and increased the GPx activity in liver homogenates compared with model control group (MDA: 7.89 ± 1.49 noml/mg prot vs 6.29 ± 1.42 noml/mg prot and 6.25 ± 2.27 noml/mg prot, respectively, P = 0.015, P = 0.015; GPx: 49.13 ± 8.72 U/mg prot vs 57.38 ± 7.65 U/mg prot and 61.39 ± 13.15 U/mg prot, respectively, P = 0.035, P = 0.003). CONCLUSION:Melatonin can ameliorate CCl 4 -induced hepatic fibrosis in rats. The protective effect of melatonin on hepatic fibrosis may be related to its antioxidant activities.

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Section: Discussionmentioning

confidence: 99%

Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats

Ren¹,

Xu²,

Qiao³

2009

WJG

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“…Lipopoplysaccharide/D-galactosamine-induced liver injury in mice was used as a positive control. 34 Liver was excised and immediately fixed in 10% neutral buffered formalin overnight. Tissue samples were processed to obtain paraffin-embedded sections, and then tissue sections were prepared and stained with hematoxylin and eosin.…”

Section: Histological Examination Of Livermentioning

confidence: 99%

Enhanced growth inhibition of metastatic lung tumors by intravenous injection of ATRA-cationic liposome/IL-12 pDNA complexes in mice

et al. 2010

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Interleukin 12 (IL-12) is a proinflammatory cytokine with antitumor activity. All-trans-retinoic acid (ATRA) exerts antitumor effects by regulating a variety of gene expressions, including tumor necrosis factor receptor 1 (TNFR1), increases the number of TNFR1 and potentiates TNF-a-induced apoptosis in cancer cells. In this study, ATRA-incorporated cationic liposome (ATRA-cationic liposome)/ IL-12 plasmid DNA (pDNA) complexes were prepared to improve therapeutic efficacy of cationic liposome/IL-12 pDNA complexes in a mouse model of metastatic lung tumor after intravenous injection. IL-12 production in lungs by ATRA-cationic liposome/IL-12 pDNA complexes was comparable with that by cationic liposome/IL-12 pDNA complexes. The number of metastatic tumor cells (colon26/Luc) was quantitatively evaluated by measuring luciferase activity. ATRA-cationic liposome/IL-12 pDNA complexes reduced the number of colon26/Luc cells and tumor nodules in lungs. ATRA-cationic liposome/IL-12 pDNA complexes significantly prolonged the survival time of mice, whereas cationic liposome/IL-12 pDNA only slightly prolonged it. ATRA-cationic liposome/IL-12 pDNA complexes increased the TNFR1 mRNA upregulation and the number of apoptotic cells in the lung. Moreover, reduced serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were observed in mice treated with ATRA-cationic liposome/IL-12 pDNA complexes. These results suggest that intravenous injection of ATRA-cationic liposome/IL-12 pDNA complexes is an effective method for the treatment of lung metastasis in mice.

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“…32 Backed up by many studies, our mice became sluggish, innert and prostated after intraperitoneal injection of LPS/Endotoxin with highly deranged ALT and AST values and marked inflammation on liver cross sections. 21,23,33,34 An ideal antioxidant should be versatile and comprehensive with throughout body distribution. It should also readily cross biological barrier and available in adequate concentration when required.…”

Section: Discussionmentioning

confidence: 99%

“…Melatonin successfully restored LPS evoked alterations in serum ALT levels and hepatic morphology, de-escalated LPS induced hepatic caspase-3 and TNF-α activity along with intensifying hepatic anti-oxidants concentration. 34 Melatonin pretreatment is also stated to preserve hepatic function, microcirculation and redox state in animal model of hemorrhagic shock.…”

Section: Discussionmentioning

confidence: 99%

Comparative efficacy of melatonin in attenuation of endotoxin/LPS induced hepatotoxicity in BALB/c mice

Khan¹,

Afzal²,

Rauf³

et al. 2018

Int J Basic Clin Pharmacol

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Background: Sepsis is characterized by overwhelming surge of cytokines and oxidative stress to one of many factors, gram negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damage including hepatotoxicity. The present study was aimed to ascertain the adequacy of melatonin (10mg/kg i.p), and its comparability with dexamethasone (3mg/kg i.p), delivered separately and collectively in endotoxin induced hepatotoxicity.Methods: The number of animals in each group was six. Endotoxin/LPS induced hepatotoxicity was reproduced in mice by giving LPS of serotype E. coli intraperitoneally. Preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas therapeutic potential of the experimental agent was searched out via post LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with histopathological examination of liver tissue.Results: Melatonin was prosperous in aversion (Group 3) and curation (Group 4) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes on liver sections (p≤0.05). Dexamethasone given before (Group5) and after LPS (Group 6) significantly (p≤0.05) attenuated LPS generated liver injury. Combination therapy with dexamethasone in conjunction with melatonin (Group 7) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably, however the result was comparable to single agent therapy.Conclusions: Melatonin set up promising results in endotoxin induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis induced liver failure. Combination therapies however generated no synergistic results.

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Melatonin attenuates lipopolysaccharide (LPS)-induced apoptotic liver damage in d-galactosamine-sensitized mice

Cited by 79 publications

References 52 publications

Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats

Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats

Enhanced growth inhibition of metastatic lung tumors by intravenous injection of ATRA-cationic liposome/IL-12 pDNA complexes in mice

Comparative efficacy of melatonin in attenuation of endotoxin/LPS induced hepatotoxicity in BALB/c mice

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