Olalekan E. Odeleye

Vitamin E reduction of lipid peroxidation products in rats fed cod liver oil and ethanol

The purpose of this study was to investigate the effects of vitamin E supplementation on ethanol- and cod liver oil-induced lipid peroxidation. Adult male rats received diets containing ethanol, cod liver oil and supplemented with vitamin E for 28 days. Following treatment, hepatic conjugated dienes, lipid fluorescence, and exhalation of ethane were measured as indices of lipid peroxidation. Ethane expiration over a 3-hour period was reduced by 96% in rats fed ethanol supplemented with vitamin E. Exhalation of ethane was increased by CLO feeding but was reduced 89% in the CLO-fed rats supplemented with vitamin E. In addition, ethane production was elevated in rats fed ethanol plus CLO compared to rats fed diets containing CLO supplemented with vitamin E. Supplementation of the CLO diet with vitamin E also significantly decreased hepatic conjugated fatty acid dienes levels. Levels of hepatic conjugated fatty acid dienes from rats fed ethanol plus vitamin E were reduced 91% compared to rats fed ethanol diets. Additionally, hepatic lipid fluorescence expressed as per mg of hepatic phospholipid basis was also significantly increased in rat groups fed vitamin E, ethanol, and cod liver oil diets. Where vitamin E was added to these same diets a significant decrease of hepatic lipid peroxidation products occurred. The observed reduction in lipid peroxidation by vitamin E may be useful to retard lipid peroxides derived materials involved in the development of alcoholic liver diseases.

Enhancement of cocaine-induced hepatotoxicity by ethanol

The contribution of moderate ethanol consumption on cocaine induced hepatotoxicity and the role lipid peroxidation plays as a possible mechanism of such increased hepatotoxicity were evaluated. Male C57BL/6 mice were injected interperitoneally (i.p.) with increasing doses of cocaine, from 10 to 50 mg/kg body weight daily and simultaneously fed a liquid diet containing 28% of the calories as ethanol for 5 or 9 weeks. Control mice received saline (i.p.) and an isocaloric carbohydrate diet. Lipid fluorescence and conjugated dienes of extracted lipids and amounts of malondialdehyde (MDA) were evaluated as indices of lipoperoxidation. In addition, serum alanine aminotransferase and aspartate transaminase were measured as indicators of liver injury and cellular death. After 9 weeks, ethanol consumption during cocaine treatment increased hepatic lipid fluorescence, conjugated dienes and MDA about twofold over mice-treated with cocaine alone. Similarly, serum transaminases were 2.8-6-fold greater in mice consuming alcohol and treated with cocaine than in mice treated with cocaine only. Histological examination of livers from mice fed ethanol during treatment with cocaine exhibited increased hepatic injuries and necrosis. The data suggest that ethanol exacerbates cocaine-induced hepatotoxicity via increases in free radical activity and hepatic lipid peroxidation.

Alcohol stimulation of lipid peroxidation and esophageal tumor growth in mice immunocompromised by retrovirus infection

Tumor appearance can be accelerated in the immunodeficient and immunosuppressed animal. The role of lipid peroxidation and immune dysfunction induced by retrovirus and ethanol treatments on cancer promotion were investigated. Following the initiation of esophageal cancer by methylbenzylnitrosamine, ethanol consumption and retrovirus infection individually and concomitantly increased growth of esophageal tumors. Dietary supplementation with vitamin E reduced the size and frequency of the developed tumors. Tumor growth modifications in the vitamin E supplemented animals may be due to changes in T-cell numbers and functions stimulated by vitamin E. In addition, increased production of free radicals following ethanol treatment and retrovirus infection, and the suppression of these formations lipid peroxide by vitamin E is accompanied by lower incidence and size of tumors. Thus, the mechanisms of tumor enhancement observed in immunocompromised animals may include a combination of immunomodulation and modification of oxidant production by ethanol consumption and retrovirus infection.

Dietary polyunsaturated fatty acid promote peroxidation and its possible role in the promotion of cancer.

It is known that an interplay between dietary, hereditary and environmental factors initiate and/or promote cancer. Several factors associated with high risk of the development of diseases including cancer have been identified. Included in these is the amount and type of dietary fat. Circumstantial evidence provided by epidemiological studies is further supported by laboratory models that provide strong correlation between dietary fat and cancer. These studies have consistently shown that high dietary fat level of 20 percent (w/w) or 40 percent by calories promote spontaneous or induced mammary tumor growth in rats and mice (Tinsley et al., 1981, Carrol et al., 1970). Polyunsaturated fatty acid containing several double bonds are unstable molecules and are readily oxidized by non-specific and specific lipoxygenases and cyclo-oxygenase enzymes systems to yield free radicals and peroxides, which are toxic to cells. Although the peroxidation of lipids have been involved in certain forms of tissue pathology and tumor growth, the mechanism and role of these fatty acids in the development of tumors has not been completely defined. Therefore, the effect of dietary cod liver oil, a polyunsaturated fatty acid, in vivo -1-lipid peroxidation as measured by ethane exhalation was investigated.

Effect of ethanol consumption and vitamin E supplementation on in vivo lipid peroxidation in rats

Abstract This study investigated the effects of short and long term vitamin E supplementation on ethanol induced lipid peroxidation in rats. Groups of rats were fed liquid diets in which ethanol provided 36% of the total calories (v/v) for 28 days or 18 months. The 28-day fed rats received supplemental alpha tocopherol 142 IU/kg of diet while those fed ethanol for 18 months were injected i.p. with 528 IU alpha tocopherol/kg body weight/day for 2 days prior to termination. At the end of the feeding period, ethane exhalation, conjugated dienes and lipid fluorescence were estimated as indices of free radical mediated products. Rats fed the ethanol diets for 28 days and 18 months exhaled more ethane than pair-fed controls. Increases in conjugated dienes and lipid fluorescence were observed in both the 28 day and 18 month groups of alcohol fed rats (p

Vitamin E attenuation of the effects of chronic ethanol and cod liver oil consumption on rat liver lipid composition

Abstract We investigated the effects of dietary vitamin E supplementation on the modulatory actions of chronic ethanol and cod liver oil (CLO) feeding by measuring the fatty acid composition of hepatic lipids. Rats were fed diets that provided 35% of total calories as lipids and 36% of the calories as ethanol for 28 days. In these diets, cod liver oil replaced safflower, corn and olive oils low in omega-3-unsaturated fatty acids but high in the omega 6 unsaturated fatty acids. Some diets were also supplemented with 142 IU of vitamin E per kg of diet. Hepatic cholesterol, phospholipids and triglyceride levels were 30–100% greater in rats fed alcohol with or without vitamin E supplementation. Addition of dietary CLO reduced liver cholesterol and the cholesterol: phospholipid ratio but increased the phospholipid and triglyceride levels. Supplemental vitamin E in the CLO fed rats elevated the levels of hepatic phospholipids and cholesterol. The vitamin E-related alterations in hepatic lipids were also reflected by changes in hepatic fatty acid (FA) composition in rats fed ethanol and CLO. The alterations in the fatty acid profile indicated that both ethanol and CLO consumption altered hepatic FA profile. Ethanol metabolism by rats fed the Lieber-DeCarli (LD) diets increased hepatic levels of myristic, palmitoleic and oleic acid levels and decreased the level of linoleic acid despite diet type. Ethanol metabolism slightly decreased hepatic palmitate levels in rats fed the LD-diet but did not alter hepatic palmitate levels in rats fed the CLO-diets, and had no effect on hepatic stearate levels in rats fed the LD diet but significantly increased hepatic stearate levels in rats fed the CLO-diet. Hepatic oleic acid levels were not altered in rats fed ethanol in the CLO-diets.

Effects of Alcohol and Cocaine Abuse on the Antioxidant Systems, Nutritional Status, and Liver Damage

It has been known for several years that the abuse of drugs such as alcohol (ethanol) and cocaine disrupt hepatic structure and functions. The mechanisms of these drug-induced hepatotoxicities are nowthoughtto be intricately related to changes in the functional activitiesof inherent enzyme antioxidant systems (e.g., superoxide dismutase, catalase, glutathione peroxidases, and the selenoenzymes). These systems and the dietary antioxidant status1, 4of tocopherols, ascorbate, and beta-carotene protect the biological system against oxidative damage.5, 8 The ability of the hepatic cells to maintain their viability and integrity against insults from xenobiotics, including commonly used drugs of abuse, is in part dependent on these antioxidant defense mechanisms. The role of xenobiotics generating free radicals and their conversion to reactive electrophiles generating species during their intracellular metabolic and detoxification process and their role in cellular damage is fully elucidated.9, 10 The generation and role of free radicals in liver damage is reviewed in another chapter of this volume.

Composition of Hepatic Lipids after Ethanol, Cod Liver Oil and Vitamin E Feeding in Rats

One of the numerous metabolic effects of alcohol consumption is its altering the metabolism of fatty acids in tissues. This alterations lead to an increase in the ratio of linoleic to arachidonic acid in the phospholipid fraction of the tissues (Ailing et al., 1984, Reitz 1979). The additional associated depletion of the alpha-tocopherol (Vitamin E) content of cell membranes following prolonged ethanol administration (Bjorneboe et al., 1987) suggests that increased lipid peroxidation may play a role in the pathogenesis of alcoholic fatty liver. If increased peroxidation of membrane lipids can lead to the disruption of the structural and functional properties of the membranes, then it might be expected that the fluidity and composition of the liver would be altered. Such an observation has been confirmed (Chin et al., 1977). It would, therefore, follow that such alterations may be prevented by a dietary antioxidant such as alpha tocophetol. In this study, the development of liver membrane proxidation and alcoholic fatty liver was promoted through chronic ethanol and cod liver oil. Supplementation of the diets with vitamin E was used to study the role of vitamin E in preventing hepatic fatty acid changes.