Ethanol dosage regimes in studies of ethanol toxicity: influence of nutrition and surgical interventions

Abstract

In this review we consider some of the practical facets of acute and chronic drug regimes. In particular, we illustrate our arguments with specific reference to alcohol and draw attention to methodological constraints that might alter biochemical or physiological processes. These includes the imposition of nutritional abnormalities and surgical procedures. These two areas are highlighted because there is evidence to show that they have marked influences on metabolic parameters, exemplified by tissue protein synthesis. In general, there is no controversy as to methods for acute studies with alcohol, although some reports have failed to investigate whether intravenous, intragastric or intraperitoneal regimes more accurately mimic the clinical situation. With regard to chronic feeding regimes, evidence is provided to support the argument that, currently, the most appropriate feeding protocol ensures that both control and treated groups receive identical amounts of nutrients albeit with differences in the calories apportioned to ethanol, which is substituted by isocaloric glucose or other carbohydrates in controls. However, there are still other methods being employed: these are subject to misinterpretation as the principle of ensuring that control and ethanol-fed rats receive identical amounts of nutrients, is ignored. In this review we also draw attention to the fact that surgical procedures, which are often employed to facilitate the measurement of body parameters (for example, implantation of cannulae), themselves alter tissue metabolism. The importance of this relates to the concept of metabolic superimposition, which implicates interacting responses when two or more stresses (i.e. surgery and drug administration) are superimposed.

Acute and chronic effects of alcohol exposure on skeletal muscle c-myc, p53, and Bcl-2 mRNA expression

“…There was no restriction on the amount of alcohol consumed by these rats. Controls were pair-fed the same diet in which ethanol was replaced by isocaloric glucose (48). After 6-7 wk (specifically, 44 and 45 days for female rats and 46-48 days for males), mean body weights of female control and ethanol-fed animals were 0.184 and 0.175 kg, respectively, whereas corresponding male rats weighed 0.215 and 0.199 kg, respectively (17).…”

“…Rats were subjected to a Lieber-DeCarli alcohol-feeding regimen in which treated rats were fed a nutritionally complete liquid diet containing 35% of total calories as ethanol ad libitum (48). Details of the diets are given here, and see also Tables 1 and 2.…”

“…We used well-characterized protocols for investigating either the long-or short-term effects of alcohol (48). We compared the responses of male and female rats to chronic ethanol feeding and then investigated the acute effects of alcohol in the presence of cyanamide or starvation.…”

Oxidants antioxidants and alcohol implications for skeletal and cardiac muscle

“…Assessment of folate, pyridoxine, riboflavin, thiamine, vitamin B12, vitamin D and general food intakes indicates that, tentatively, the myopathy is not nutritional in origin (1)(2)(3)(4). However, compared to either non-misusing controls or non-myopathic alcoholics, serum selenium and alphatocopherol concentrations are lower in myopathic alcoholics (8).…”

Acute alcohol administration inhibits the refeeding response after starvation in rat skeletal muscle

“…We did not introduce a fed animal group, since we have described in detail the synthesis rates of muscle proteins in fed (ad libitum-fed controls), starved, and refed animals (either chow solid diet or enteral or parenteral feeds) (19,21). In addition, we employed a standard regimen of acute ethanol dosage, namely 75 mmol/kg body wt (22). With this regimen, pathophysiological plasma alcohol concentrations are achieved, for example, ϳ450 mg/dl at 20 min, which drops steadily to ϳ250 mg/dl after 2.5 h (27).…”