Zinc Supplementation Prevents Alcoholic Liver Injury in Mice through Attenuation of Oxidative Stress

Zhou, Zhanxiang; Wang, Lipeng; Song, Zhenyuan; Saari, Jack T.; McClain, Craig J.; Kang, Y. James

doi:10.1016/s0002-9440(10)62478-9

Cited by 174 publications

(140 citation statements)

References 49 publications

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“…Although there are not any studies on the effectiveness of zinc in spinal cord I/R injuries, it is stated that zinc supplementation causes an increase in the levels of antioxidants such as GSH and GPx. 29 When the XO activities in the spinal tissue were investigated, it was found that these parameters considerably increased especially in the I/R group. However, there was a remarkable decrease in these parameters in groups in which zinc, melatonin and melatonin þ zinc applications were implemented.…”

Section: Discussionmentioning

confidence: 99%

The effects of prophylactic zinc and melatonin application on experimental spinal cord ischemia–reperfusion injury in rabbits: experimental study

et al. 2007

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Study design: Experimental study. Objectives: To determine the neuroprotective effects of zinc and melatonin on spinal cord ischemia-reperfusion (I/R) injuries of rabbits. Setting: The Experimental Research Centre of Selc¸uk University, Konya, Turkey. Methods: Twenty-four male rabbits underwent spinal cord ischemia by clamping the thoracoabdominal aorta for 20 min. Twenty minutes before the aortic clamping, animals received zinc, melatonin or a combination of both. Neurological examination of the animals was performed three times during reperfusion period. The animals were killed 24 h after reperfusion. Spinal cord samples were taken for biochemical and histopathological evaluation. Results: Pre-treated animals with zinc, melatonin or combination displayed better neurological outcomes than the I/R group (Po0.05). Zinc, melatonin and combined treatment prevented spinal cord injury by reducing apoptosis rate (Po0.05) and preserving intact ganglion cell numbers (Po0.05). Zinc pre-treatment protected spinal cord by preventing malondialdehyde (MDA) formation (P ¼ 0.002), increasing glutathione peroxidase (GPx) activity (P ¼ 0.002) and decreasing xanthine oxidase enzyme activity (P ¼ 0.026) at molecular level. Melatonin treatment also resulted with MDA formation (P ¼ 0.002), increased GPx activity (P ¼ 0.002) and decreased xanthine oxidase activity (P ¼ 0.026). Conclusion:The results of the study showed that prophylactic zinc and melatonin use in spinal cord I/R not only suppressed lipid peroxidation by activating antioxidant systems but also had significant neuroprotective effects by specifically improving the neurological and histopathological situation.

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Section: Discussionmentioning

confidence: 99%

The effects of prophylactic zinc and melatonin application on experimental spinal cord ischemia–reperfusion injury in rabbits: experimental study

et al. 2007

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“…Zn has catalytic and structural roles in more than 300 metalloenzymes, as well as regulatory roles in diverse cellular processes such as signaling transduction and gene expression (McCall et al, 2000). Many studies have demonstrated that Zn per se functions as antioxidant and also plays an important role in regulation of cellular glutathione (GSH) (Parat et al, 1997;Powell, 2000;Zhou et al, 2005). Although GSH is the most important molecule involved in cellular antioxidant defense, radical scavenging activity of GSH is 300-times lower than that of MT (Thornalley and Vasak, 1985).…”

Section: Effect Of Zn and CD Against Acute Ccl 4 Toxicitymentioning

confidence: 99%

Carbon tetrachloride-induced lethality in mouse is prevented by multiple pretreatment with zinc sulfate

et al. 2016

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-Carbon tetrachloride (CCl 4 ) is commonly used as a chemical inducer of experimental liver injury. Several compounds have been demonstrated to attenuate the hepatic damage caused by sublethal doses of CCl 4 . However, rescue from lethal toxicity of CCl 4 has not been reported. In the present study, we evaluated the protective effect of metallothionein (MT), an endogenous scavenger of free radicals, on CCl 4 -induced lethal toxicity of mice. To induce MT production in male ddY mice, we administered Zn (as ZnSO 4 ) at 50 mg/kg as a once-daily subcutaneous injection for 3 days prior to a single intraperitoneal administration of 4 g/kg CCl 4 . Animals were observed for mortality every 3 hr for 24 hr after CCl 4 injection. Liver damage was assessed by determining (in a subset of these mice) blood levels of alanine aminotransferase (ALT; a marker of liver injury) and liver histopathology at 6 hr after CCl 4 injection. Our results showed that three times pretreatment with Zn yielded > 40-fold induction of hepatic MT protein levels compared to control group. Zn pretreatment completely abolished the CCl 4 -induced mortality of mice. We also found that pretreatment of mice with Zn significantly decreased the ALT levels and reduced the histological liver damage as assessed at 6 hr post-CCl 4 . These findings suggest that prophylaxis with Zn protects mice from CCl 4 -induced acute hepatic toxicity and mortality, presumably by induction of radical-scavenging MT.

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“…Numerous other antioxidants show efficacy in treating fatty liver diseases and include Nacetylcysteine [166], zinc [167,168], silymarin [169], and ursodeoxycholic acid [170], just to name a few. Please refer to the following excellent review articles for additional information on antioxidant therapy for treatment of fatty liver diseases from multiple causes [144,[171][172][173][174].…”

Section: Are Antioxidants Feasible Treatments For Fatty Liver Disease?mentioning

confidence: 99%

Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

Mantena

King

Andringa

et al. 2008

Free Radical Biology and Medicine

388

302

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Fatty liver disease associated with chronic alcohol consumption or obesity/type 2 diabetes has emerged as a serious public health problem. Steatosis, accumulation of triglyceride in hepatocytes, is now recognized as a critical "first-hit" in the pathogenesis of liver disease. It is proposed that steatosis "primes" the liver to progress to more severe liver pathologies when individuals are exposed to subsequent metabolic and/or environmental stressors or "second-hits". Genetic risk factors can also influence the susceptibility and severity of fatty liver disease. Furthermore, oxidative stress, disrupted nitric oxide (NO) signaling, and mitochondrial dysfunctional are proposed to be key molecular events that accelerate or worsen steatosis and initiate progression to steatohepatitis and fibrosis. This review article will discuss the following topics regarding the pathobiology and molecular mechanisms responsible for fatty liver disease: 1) the "two-hit" or "multi-hit" hypothesis; 2) the role of mitochondrial bioenergetic defects and oxidant stress; 3) interplay between NO and mitochondria in fatty liver disease; 4) genetic risk factors and oxidative stress responsive genes; and 5) the feasibility of antioxidants for treatment.

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Zinc Supplementation Prevents Alcoholic Liver Injury in Mice through Attenuation of Oxidative Stress

Cited by 174 publications

References 49 publications

The effects of prophylactic zinc and melatonin application on experimental spinal cord ischemia–reperfusion injury in rabbits: experimental study

The effects of prophylactic zinc and melatonin application on experimental spinal cord ischemia–reperfusion injury in rabbits: experimental study

Carbon tetrachloride-induced lethality in mouse is prevented by multiple pretreatment with zinc sulfate

Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

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