Lipid Peroxidation: A Mechanism for Ethanol-Associated Testicular Injury in Rats*

Rosenblum, Elaine; Gavaler, Judith S.; Thiel, David H. Van

doi:10.1210/endo-116-1-311

Cited by 49 publications

(32 citation statements)

References 22 publications

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“…It is known that ethanol induces apoptotic cell death in testicular germ cells and suppresses spermatogenesis [14]. Previous our study demonstrated that ethanol significantly increased the number of apoptotic cells in both spermatogonia and spermatocytes [11].…”

Section: Discussionsupporting

confidence: 50%

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Ethanol Exposure Suppresses Survival Kinases Activation in Adult Rat Testes

Koh

2007

The Journal of Veterinary Medical Science

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ABSTRACT. The present study was designed to evaluate whether ethanol suppresses survival-signaling pathways in rat testes. Ethanol (1.5 g/kg or 3 g/kg i.p., 15% v/v in saline) was administrated to adult male rats for 10 days. Ethanol treatment significantly increased the number of TUNEL-positive cells in rat testes. Potential activation was measured by phosphorylation of Akt and Erk1/2 using Western blot analysis. Ethanol decreased the levels of activated survival kinases, pAkt and pErk1/2. The phosphorylation of Bad at Ser112 and Ser136 was decreased in ethanol-treated animals in comparison to saline-treated animals. Moreover, the interaction of pBad with 14-3-3 was decreased by ethanol exposure. In conclusion, our findings suggest that ethanol induces apoptotic cell death by suppressing the activation of survival kinases and the phosphorylation of their downstream targets in rat testes.

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Section: Discussionsupporting

confidence: 50%

“…It is known to cause serious reproductive disorders, including testicular atrophy, accessory reproductive organ dysfunction, and infertility [1,5,6]. In particular, ethanol produces an oxidative stress within the testis and enhances apoptotic cell death [11,14,18].…”

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confidence: 99%

Ethanol Exposure Suppresses Survival Kinases Activation in Adult Rat Testes

Koh

2007

The Journal of Veterinary Medical Science

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“…The mechanisms of this injury were previously studied. One is that ethanol metabolism produces an oxidative stress within the testes [15]; another is that ethanol exposure changes either testosterone [16] or esterone levels [17]. In addition, Zhu et al showed that ethanol exposure adversely affected the secretory function of Sertoli cells [18] and their recent research revealed enhanced apoptosis within the testes after chronic ethanol exposure [19].…”

Section: Introductionmentioning

confidence: 99%

Enhancement of germ cell apoptosis induced by ethanol in transgenic mice overexpressing Fas Ligand

Jiang

Hua

et al. 2003

Cell Res

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It was suggested that chronic ethanol exposure could result in testicular germ cell apoptosis, but the mechanism is still unclear. In the present study, we use a model of transgenic mice ubiquitously overexpressing human FasL to investigate whether Fas ligand plays a role in ethanol-induced testicular germ cell apoptosis. Both wild-type (WT) mice and transgenic (TG) mice were treated with acute ethanol (20% v/v) by introperitoneal injection for five times. After ethanol injection, WT mice displayed up-regulation of Fas ligand in the testes, which was shown by FITCconjugated flow cytometry and western blotting. Moreover, TG mice exhibited significantly more apoptotic germ cells than WT mice did after ethanol injection, which was demonstrated by DNA fragmentation, PI staining flow cytometry and TUNEL staining. In addition, histopathological examination revealed that degenerative changes of epithelial component of the tubules occurred in FasL overexpressing transgenic mice while testicular morphology was normal in wild-type mice after acute ethanol exposure, suggesting FasL expression determines the sensitivity of testes to ethanol in mice. In summary, we provide the direct evidences that Fas ligand mediates the apoptosis of testicular germ cells induced by acute ethanol using FasL transgenic mice.

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“…These various findings have been interpreted as evidence that lipid peroxidation has occurred in the liver as a result of ethanol metabolism. Lipid peroxidation has also been proposed as a mechanism of ethanol-induced toxicity in the heart (10), gastric mucosa (11), and testes (12). However, the role of peroxidative events in the development of human alcoholrelated disease is highly controversial.…”

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confidence: 99%

Reactive free radical generation in vivo in heart and liver of ethanol-fed rats: correlation with radical formation in vitro.

Reinke

Lai

Dubose

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

204

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Rats fed a high-fat ethanol-containing diet for 2 weeks were found to generate free radicals in liver and heart in vivo. The radicals are believed to be carbon-centered radicals, were detected by administering spin-trapping agents to the rats, and were characterized by electron paramagnetic resonance spectroscopy. The radicals in the liver were demonstrated to be localized in the endoplasmic reticulum. Rats fed ethanol in a low-fat diet showed significantly less free radical generation. Control animals given isocaloric diets without ethanol showed no evidence of free radicals in liver and heart. When liver microsomes prepared from rats fed the high-fat ethanol diet were incubated in a system containing ethanol, NADPH, and a spin-trapping agent, the generation of 1-hydroxyethyl radicals was observed. The latter was verified by using "3C-substituted ethanol. Microsomes from animals fed the high-fat ethanol-containing diet had higher levels of cytochrome P-450 than microsomes from rats fed the low-fat ethanol-containing diet. The results suggest that the consumption of ethanol results in the production of free radicals in rat liver and heart in vivo that appear to initiate lipid peroxidation.Chronic excessive use of alcohol by humans results in liver disease (1, 2) characterized by fatty infiltration, which can lead to fibrotic degeneration and necrosis (1,3,4). However, the mechanisms leading to the development of alcoholic liver disease remain unclear. Lipid peroxidation was linked to ethanol consumption by Di Luzio and coworkers (5, 6), who reported that antioxidants prevented the development of fatty liver after a large acute dose of ethanol. Investigations by others have subsequently indicated that lipid peroxidation appears to occur in the livers of animals soon after the administration of an acute dose of alcohol. Much of the evidence for these claims has been based on the thiobarbituric acid assay for malondialdehyde in livers of animals treated with ethanol (7, 8), but increases in conjugated dienes and chemiluminescence as well as decreases in hepatic glutathione have also been reported (8). In addition, Muller and Sies (9) have reported an enhanced production of ethane and n-pentane, which are believed to be products of the peroxidative degradation of membrane lipids, during the metabolism of ethanol by perfused livers. These various findings have been interpreted as evidence that lipid peroxidation has occurred in the liver as a result of ethanol metabolism. Lipid peroxidation has also been proposed as a mechanism of ethanol-induced toxicity in the heart (10), gastric mucosa (11), and testes (12). However, the role of peroxidative events in the development of human alcoholrelated disease is highly controversial.Mechanisms that may initiate lipid peroxidation after ethanol exposure are also uncertain. Several laboratories have presented evidence that chronic ethanol feeding stimulates the production of hydroxyl radicals by liver microsomes (13,14). If this type of radical production occurs in the...

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Lipid Peroxidation: A Mechanism for Ethanol-Associated Testicular Injury in Rats*

Cited by 49 publications

References 22 publications

Ethanol Exposure Suppresses Survival Kinases Activation in Adult Rat Testes

Ethanol Exposure Suppresses Survival Kinases Activation in Adult Rat Testes

Enhancement of germ cell apoptosis induced by ethanol in transgenic mice overexpressing Fas Ligand

Reactive free radical generation in vivo in heart and liver of ethanol-fed rats: correlation with radical formation in vitro.

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