Ethanol-Induced Lipid Peroxidation and Oxidative Stress in Extrahepatic Tissues

Abstract

An ethanol-induced oxidative stress is not restricted to the liver, where ethanol is actively oxidized, but can affect various extrahepatic tissues as shown by experimental data obtained in the rat during acute or chronic ethanol intoxication. Most of these data concern the central nervous system, the heart and the testes. An acute ethanol load has been reported to enhance lipid peroxidation in the cerebellum. This is accompanied by an increase in the cytosolic concentration of low-molecular-weight iron derivatives which may contribute to the generation of aggressive free radicals. The ethanol-induced decrease in the main antioxidant systems (superoxide dismutase, alpha-tocopherol, ascorbate and selenium) is a likely contributor to the cerebellar oxidative stress. Most of these disturbances can be prevented by allopurinol administration. Some experimental data support also the occurrence of pro- and anti-oxidant disturbances in the cerebellum and in other regions of the central nervous system after chronic ethanol administration. Chronic ethanol administration enhances lipid peroxidation in the heart. The increased conversion of xanthine dehydrogenase into xanthine oxidase as well as the activation of peroxisomal acyl CoA-oxidase linked to ethanol administration could contribute to the oxidative stress. Chronic ethanol administration elicits in the testes an enhancement in mitochondrial lipid peroxidation and a decrease in the glutathione level, which appear to be correlated to the gross testicular atrophy observed. Vitamin A supplementation attenuates the changes in lipid peroxidation, glutathione and testicular morphology. Whether the reported disturbances are involved in the pathogenesis of the tissue disorders observed in alcoholic patients remains unanswered.(ABSTRACT TRUNCATED AT 250 WORDS)

Antioxidant Systems and Oxidative Stress in the Testes

“…Moreover the oxidative stress associated with the diabetic condition is associated with DNA damage in the In addition to smoking, excessive alcohol consumption also has a negative effect of testicular function through the induction of oxidative stress and the concomitant disruption of testicular antioxidant status. 108,109 Furthermore, the ability of antioxidants such as vitamin C or lecithin to ameliorate this pathology, confirms the importance of oxidative stress in this context. [110][111] In addition to inducing low sperm counts and poor sperm motility, it also appears that the oxidative stress created in the Leydig cells as a consequence of chronic alcohol exposure diminishes the steroidogenic capacity of the testes, lowering circulating testosterone levels.…”

Regional selectivity in ethanol-induced pro-oxidant events within the brain

“…Smaller but significant oxidative events have been described frequently in the central nervous system after ethanol treatment [1][2][3]. The difficulty of obtaining more definitive data in this case may be due to the considerable regional heterogeneity of the central nervous system.…”

Alcohol stress, membranes, and chaperones

“…Taken together, these studies suggest that an elevated level of free radical production and oxidative stress play central roles in the pathogenesis of alcoholic liver disease (Wu and Cederbaum 2003). Furthermore, ethanol can also induce oxidative stress and depress the activity of the protective antioxidant system in extrahepatic tissues such as the heart and brain (reviewed in Nordmann et al 1990). Short-term alcohol treatment led to decreased glutathione levels in heart, liver, and gastrocnemius muscle of mice and reduced plasma superoxide dismutase capacity (Islam et al 2013).…”