Liver antioxidant defenses in mice fed ethanol and the AIN-76A diet

Chen, L.H.; Xi, S.; Cohen, Donald A.

doi:10.1016/0741-8329(95)00030-u

Cited by 52 publications

(22 citation statements)

References 21 publications

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“…Interestingly, overexpression of mitochondrial Mn-SOD had no effect on the increase in catalase due to ethanol. Importantly, these findings are consistent with other reports (41).…”

Section: Body and Liversupporting

confidence: 83%

“…These data suggest that H 2 O 2 readily diffuses into the cytosol, most likely down a concentration gradient to catalase, which is extremely abundant and highly active in hepatocytes. Moreover, others have shown (40,41), and it is also demonstrated here, that catalase activity is increased because of chronic ethanol (Table II), supporting the conclusion that catalase levels are sufficient to metabolize H 2 O 2 in liver.…”

Section: Fig 8 Effect Of Adsod2 On Neutrophils In the Liversupporting

confidence: 68%

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Overexpression of Manganese Superoxide Dismutase Prevents Alcohol-induced Liver Injury in the Rat

Wheeler

Nakagami

Bradford

et al. 2001

Journal of Biological Chemistry

188

110

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Mitochondria are thought to play a major role in hepatic oxidative stress associated with alcohol-induced liver injury. Thus, the hypothesis that delivery of the mitochondrial isoform of superoxide dismutase (Mn-SOD) via recombinant adenovirus would reduce alcohol-induced liver injury was tested. Rats were given recombinant adenovirus containing Mn-SOD (Ad.SOD2) or ␤-galactosidase (Ad.lacZ) and then fed alcohol enterally for 4 weeks. Mn-SOD expression and activity of Ad.SOD2 in liver mitochondria of infected animals was increased nearly 3-fold compared with Ad.lacZ-infected controls. Mitochondrial glutathione levels in Ad.lacZinfected animals were decreased after 4 weeks of chronic ethanol, as expected, but were unchanged in Ad.SOD2-infected animals. Alanine aminotransferase was elevated significantly by ethanol, an effect that was prevented by Ad.SOD2. Moreover, pathology (e.g. the sum of steatosis, inflammation, and necrosis) was elevated dramatically by ethanol in Ad.lacZ-treated rats. This effect was also blunted in animals infected with Ad.SOD2. Neutrophil infiltration was increased about 3-fold in livers from both Ad.lacZ-and Ad.SOD2-infected rats by ethanol treatment. Moreover, ESR-detectable free radical adducts in bile were increased about 8-fold by ethanol. Using 13 C-labeled ethanol, it was determined that nearly 60% of total adducts were due to the ␣-hydroxyethyl radical adduct. This increase in radical formation was blocked completely by Ad.SOD2 infection. Furthermore, apoptosis of hepatocytes was increased about 5-fold by ethanol, an effect also blocked by Ad.SOD2. Interestingly, tumor necrosis factor-␣ mRNA was elevated to the same extent in both Ad.lacZ-and Ad.SOD2-infected animals follows ethanol exposure. These data suggest that hepatocyte mitochondrial oxidative stress is involved in alcohol-induced liver damage and likely follows Kupffer cell activation, cytokine production, and neutrophil infiltration. These results also support the hypothesis that mitochondrial oxidant production is a critical factor in parenchymal cell death caused by alcohol.Alcoholic liver disease results from dose-and time-dependent exposure to alcohol (1), but precise mechanisms of pathology are still largely unknown. Endotoxin and Kupffer cells have been implicated in the mechanism of early alcoholinduced liver injury using the enteral feeding model of Tsukamoto-French (2). For example, endotoxin derived from the gut activates Kupffer cells in the liver (3). In support of this idea, gut sterilization with nonabsorbable antibiotics or inactivation of Kupffer cells by gadolinium chloride (GdCl 3 ) prevents alcohol-induced liver injury in this model (4, 5). Furthermore, Kupffer cells, which release effectors and cytokines, are a major source of TNF␣ 1 in the liver (6). Indeed, TNF␣ messenger RNA in liver increased after 4 weeks of treatment with ethanol (7). Moreover, early alcohol-induced liver injury was attenuated by anti-TNF␣ antibodies and largely prevented in TNF receptor 1 knockout mice (8, 9). Thus, it is clear t...

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“…Interestingly, overexpression of mitochondrial Mn-SOD had no effect on the increase in catalase due to ethanol. Importantly, these findings are consistent with other reports (41).…”

Section: Body and Liversupporting

confidence: 83%

Section: Fig 8 Effect Of Adsod2 On Neutrophils In the Liversupporting

confidence: 68%

Overexpression of Manganese Superoxide Dismutase Prevents Alcohol-induced Liver Injury in the Rat

Wheeler

Nakagami

Bradford

et al. 2001

Journal of Biological Chemistry

188

110

View full text Add to dashboard Cite

show abstract

“…GSH-Px activity depends on the balance between the levels of GSH and glutathione disulfide [32], and GSH-Px works in tandem with CAT to scavenge excess hydrogen peroxide and lipid peroxides in response to oxidative stress [33]. In the present study, we found the significantly reduced of GSHPx and CAT activities, and GSH contents in the NiCl 2 -treated groups in comparison with those in the control group, which was agree with previous studies [13] [14].…”

Section: Discussionsupporting

confidence: 82%

Effects of Nickel Chloride on Histopathological Lesions and Oxidative Damage in the Thymus

Tang¹,

Li²,

Yin³

et al. 2014

Health

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The purpose of this study was to observe the histopathological lesions and oxidative damage induced by dietary nickel chloride (NiCl 2 ) in the thymus. A total of 280 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as the control diet or the same basal diet supplemented with 300, 600, and 900 mg/kg of NiCl 2 for 42 days. In the NiCl 2 -treated groups, the broiler weight and thymic relative weight were significantly (P < 0.05 or P < 0.01) decreased. Histopathologically, thymic corpuscles were increased and enlarged; the reticular cells were degenerate and necrotic, and lymphocytes were slightly decreased and loosely arranged in the medulla of thymus in the 600 mg/kg and 900 mg/kg groups. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and the ability to inhibit hydroxy radical and glutathione (GSH) content were significantly (P < 0.05 or P < 0.01) lower in the NiCl2-treated groups than those in the control group, while MDA content was higher. The abovementioned results demonstrated that dietary NiCl 2 in excess of 300 mg/kg could reduce the broiler weight and thymic relative weight, and cause histopathological lesions and oxidative damage in the thymus, which finally impaired the thymic function.

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“…GPx works non-specifically to scavenge and decompose excess hydroperoxides including H 2 O 2 , which may be prevalent under oxidative stress [40,41] . Glutathione-Stransferase (GST) mainly detoxifies electrophilic compounds and has a well-established role in protecting cells from mutagens and carcinogens as a free radical scavenger along with glutathione [42] .…”

Section: Discussionmentioning

confidence: 99%