Effects of Gender on the Cardiac Toxicity Elicited by Chronic Ethanol Intake in Rats

Kennedy, Richard H.; Stewart, Charles L.; Light, Kim E.; Wyeth, Richard P.

doi:10.1006/taap.2002.9354

Cited by 10 publications

(8 citation statements)

References 52 publications

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“…Differences in the hormonal milieu between male and female rats have been posited to modulate sexual dimorphic responses in other organ systems (1,9,11,12,25,29,41). In this regard, we have previously reported that long-term alcohol feeding decreases the plasma and muscle content of the anabolic hormone IGF-I and that these changes are proportional to the amount of active eIF4E⅐eIF4G and the rate of protein synthesis in muscle of male rats (18).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, many of the adverse consequences of alcohol consumption, including alcoholic cardiac and skeletal muscle myopathy, develop more rapidly and require lower levels of alcohol exposure in females compared with males (9,12,27,29,38,39). These observations cannot be explained by differences in body weight, fat distribution, body water, differential rates of ethanol oxidation, or other potentially confounding variables.…”

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confidence: 99%

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Skeletal muscle protein synthesis and degradation exhibit sexual dimorphism after chronic alcohol consumption but not acute intoxication

Lang

Frost

Vary

2007

American Journal of Physiology-Endocrinology and Metabolism

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Epidemiological evidence suggests alcoholic myopathy is more severe in females than males, but comparable animal studies are lacking that make elucidating the biochemical locus for this defect problematic. The present study determined whether skeletal muscle protein synthesis and markers of degradation exhibit a sexual dimorphic response to either chronic alcohol consumption or acute intoxication. Male and female rats were fed an alcohol-containing diet, pair-fed for 26 wk (chronic), or received an intraperitoneal injection of alcohol (acute). In males, chronic alcohol decreased gastrocnemius protein synthesis by 20%. This reduction was associated with a twofold increase in the inactive eukaryotic initiation factor (eIF) 4E·4E-binding protein 1 (4E-BP1) complex and a 60% reduction in the active eIF4E·eIF4G complex. This redistribution of eIF4E was associated with decreased phosphorylation of both 4E-BP1 and eIF4G (50–55%). The phosphorylation of ribosomal protein S6 was also reduced 60% in alcohol-consuming male rats. In contrast, neither rates of protein synthesis nor indexes of translation initiation in muscle were altered in alcohol-fed female rats despite blood alcohol levels comparable to males. Chronic alcohol ingestion did not alter atrogin-1 or muscle RING finger-1 mRNA content (biomarkers of muscle proteolysis) in males but increased their expression in females 50–100%. Acute alcohol intoxication produced a comparable decrease in muscle protein synthesis and translation initiation in both male and female rats. Our data demonstrate a sexual dimorphism for muscle protein synthesis, translation initiation, and proteolysis in response to chronic, but not acute, alcohol intoxication; however, they do not support evidence indicating females are more sensitive toward the development of alcoholic skeletal muscle myopathy.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Skeletal muscle protein synthesis and degradation exhibit sexual dimorphism after chronic alcohol consumption but not acute intoxication

Lang

Frost

Vary

2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Studies evaluating contractile function in female rats following long-term ethanol consumption have found no effect of ethanol on contractile parameters [7,8]. We examined alcohol-related ventricular contractile function using a conductance-micromanometer system, which allows evaluation of in vivo left ventricular systolic and diastolic performance in a rat under loaddependent and load-independent hemodynamic conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Using an isolated atrial preparation, others have found no negative cardiovascular effects of long-term (6-month) ethanol consumption in female rats, whereas atrial developed tension was significantly decreased in male rats [7]. In a study using exclusively female rats and a Langendorff preparation to evaluate cardiac performance, Lochner et al [8] found no negative effects of long-term ethanol consumption (18 months).…”

Section: Introductionmentioning

confidence: 95%

Long-term Effects of Alcohol Consumption in Male and Female Rats

et al. 2007

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Discrepancies exist regarding potential sex differences in the effects of ethanol on the myocardium. Therefore, the aims of this study were to determine if long-term ethanol consumption was associated with the development of a dilated cardiomyopathy (CM) in female rats and, second, to determine if the absence of ovarian hormones modulated this effect. Adult male and female (n=6-8/group) sham-operated and ovariectomized (OVX) Sprague-Dawley rats received the Lieber DeCarli ethanol-containing (8% vol/vol) or control liquid diet for 8 months. All ethanol groups showed echocardiographic evidence of a cardiomyopathy; however, more significant ethanol-elicited differences were found in the male ethanol group than in either the female or female OVX groups. In addition, the male ethanol group had significant reductions in in vivo measures of contractility, such as the maximum derivative of change in systolic pressure and preload recruitable stroke work. Sex differences were also apparent in the pattern and degree of posterior and septal wall thickness changes, in that the male ethanol group had more posterior and septal wall thinning. In conclusion, similar to male rats long-term ethanol consumption in gonad-intact and OVX female rats is associated with the development of a dilated cardiomyopathy.

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“…Using an isolated atrial preparation, Kennedy et al found no negative CV effects of long-term (6-month) ethanol consumption in female rats, whereas tension was significantly decreased in male rats (85). In a study using exclusively female rats and a Langendorff preparation to evaluate cardiac performance, Lochner et al found no negative effects of long-term ethanol consumption (18 months) (86).…”

Section: The Pattern Of Drinking and Other Mediating Factorsmentioning

confidence: 99%

Alcoholic Cardiomyopathy: Pathophysiologic Insights

2014

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Alcoholic cardiomyopathy is a specific heart muscle disease found in individuals with a history of long-term heavy alcohol consumption. Alcoholic cardiomyopathy is associated with a number of adverse histological, cellular, and structural changes within the myocardium. Several mechanisms are implicated in mediating the adverse effects of ethanol, including the generation of oxidative stress, apoptotic cell death, impaired mitochondrial bioenergetics/stress, derangements in fatty acid metabolism and transport, and accelerated protein catabolism. In this review, we discuss the evidence for such mechanisms and present the potential importance of drinking patterns, genetic susceptibility, nutritional factors, race, and sex. The purpose of this review is to provide a mechanistic paradigm for future research in the area of alcoholic cardiomyopathy.

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Effects of Gender on the Cardiac Toxicity Elicited by Chronic Ethanol Intake in Rats

Cited by 10 publications

References 52 publications

Skeletal muscle protein synthesis and degradation exhibit sexual dimorphism after chronic alcohol consumption but not acute intoxication

Skeletal muscle protein synthesis and degradation exhibit sexual dimorphism after chronic alcohol consumption but not acute intoxication

Long-term Effects of Alcohol Consumption in Male and Female Rats

Alcoholic Cardiomyopathy: Pathophysiologic Insights

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