Histo-morphological, Biochemical and Neurobehavioural Evaluation of the Frontal Lobe Following Chronic Alcohol Administration in Wistar Rats
Chapter One
Aim and Objectives of the Study
Aim of the Study
This study was aimed at evaluating the effect of chronic alcohol consumption on the frontal lobe of the cerebrum of adult Wistar rats
Objectives of the Study
The objectives of the study were to evaluate the frontal lobe following chronic alcohol administration;
- hist-architecture of frontal
- on cognitive activities, aggression and anxiety using neuro-behavioural
- Activities of superoxide dismutase and catalase, glutathione and malondialdehyde
Chapter Two
LITERATURE REVIEW
Alcohol Absorption
The alcohol molecule is a small polar molecule with molecular weight of 46.068 g/mol and density of 0.7892g/ml having both lipophilic and hydrophilic characteristics (Ferreira and Willoughby, 2008). The amphipathic qualities of alcohol help to explain its pharmacokinetics within the body. The lipophilic qualities explain how alcohol is absorbed by passive diffusion across the cell membranes without the need for modification. The hydrophilic combined with the polar properties of the alcohol molecule explain how alcohol is completely soluble in water and thus has a similar volume of distribution to total body water (TBW).
Blood alcohol concentration (BAC) is determined by the various factors that affect the rate atwhich alcohol is absorbed (including the amount and concentration of alcohol ingested and the quantity and composition of food in the stomach),distributed, metabolized and excreted from the body (Mumenthaler et al., 1999). Following oral administration absorption and distribution determines the proportion and rate at which orally ingested alcohol reaches the blood and body tissues (bioavailability).
As alcohol is a small water soluble molecule that can cross cell membranes, it is absorbed from both the stomach (20 %) and the upper small intestine (80 %) (Paton, 2005 and Norberg et al., 2003). The rate of absorption varies significantly in both intra-individual and inter-individual comparisons even after standardised conditions (Fraser, 1997). This suggests that intra-individual variability is due to variation in gastrointestinal function (gastric emptying, intestinal transit time, and portal blood flow). The rate of gastric emptying has a significant impact on the speed at which alcohol is absorbed, because alcohol isabsorbed much faster from the small intestine, than it is from the stomach (Fraser, 1997). Factors that affect alcohol availability and gastric emptying will greatly influence the rate of absorption. For example, theconsumption of alcohol with food inhibits absorption because approximately 20% of the ingested alcohol isoxidised before it can be absorbed (Paton, 2005 and Norberg et al., 2003). The speed ofabsorption is also influence by variation in portal blood flow because alcohol crosses the biologicalmembrane by passive diffusion (Paton, 2005; Ferreira and Willoughby, 2008) thus good blood flow will maintain the concentration gradient andpromote absorption. Any stimulation of the sympathetic nervous system (e.g. emotional state orexercise) will reduce portal blood flow and gastric motility thus decreasing alcohol absorption. The typeof drink consumed also plays a role. Drinks with alcohol content between 20-30% are absorbed quickest (Paton, 2005). Whereas drinks with a higher alcohol content are absorbed more slowly, because an alcohol content over 30% irritates the gastric mucosa increasing mucus secretion and decreasing gastric emptying. Thus, drinks with an alcohol content above 30% can cause a faster rise in BAC if served diluted with a mixer, than if they are serve without dilution. This is especially true if the mixer is a carbonated drink as this can also increase the rate of absorption (Paton, 2005).
Alcohol Distribution
The bioavailability of alcohol is reduced by first pass metabolism (FPM). Oxidation of alcohol by gastric alcohol dehydrogenase (ADH) in the gastric mucosa accounts for a small proportion of FPM, but the majority occurs via oxidation by ADH in the liver hepatocytes (Ferreira and Willoughby, 2008; Vonghia, et al., 2008; Paton, 2005; Fraser, 1997). The proportion of alcohol that is absorbed, and escapes FPM enters the systemic circulation and is rapidly distributed throughout the body tissues via the blood plasma until an equilibrium between the BAC and tissue concentration is reached (Ferreira and Willoughby, 2008). The time until equilibrium is dependent upon the permeability (water content), rate of blood flow and mass of the tissue (Mumenthaler, et al., 1999), but is generally achieve within 1-2 hours (Ferreira and Willoughby, 2008). The same amount of alcohol absorbed can affect different people in different ways (Paton, 2005). Differences in TBW will influence alcohol pharmacokinetics because it determines the volume of distribution available for alcohol distribution within the body. Alcohol is preferentially distributed in tissues with higher water contents and a good blood supply (e.g. brain and skeletal muscle). Body composition is therefore an important consideration in pharmacokinetic studies (Jones, 2007) because both body size and composition will have a significant impact on the volume of distribution. Females generally have a proportionately smaller lean body mass and a smaller blood volume (Paton, 2005 and Mumenthaler, et al., 1999). The result is a lower volume of distribution and higher BAC when females ingest the same amount of alcohol as men (Mumenthaler, et al., 1999). It has also been suggested that higher BAC may be due to lower FPM by gastric ADH in the gastric mucosa of females (Vogel-Sprott, 1992). This would increase the bioavailability of alcohol resulting in increased BAC.
However, the ability of gastric ADH to metabolizesignificant amounts of alcohol has been questionedbecause its activity is 100 times lower than hepatic ADH (Fraser, 1997) and more recent studies have failed tosupport this finding (Yin, et al., 1997).
Chapter Three
MATERIALS AND METHOD
Experimental Animals
For the purpose of this study, thirty-two (32)apparently healthy Wistar rats of both sexes were obtained from the Department of Human Anatomy Bello University, Zaria. The animals were housed in the animals House of the Department and were acclimatized for one weeks before the commencement of the experiment.
All animals were maintained on standard animal diet feeds and water. The animals were categorized into control and treatment groups. The animals were weighed before the commencement of the experiment and animals weighed between 80 and 120g.
Animal Feed
Pelletized growers feed manufactured by The Grand Cereals and Oil Mills Limited (GCOML) was obtained and used to feed the animals for the experiment.
Composition of feed include Crude protein (13%), Crude fibre (8%), Fat (15%), Calcium (0.80%),and phosphorus (0.40%).Other constituents include: cereals, essential amino acids/proteins, vegetables, animal protein, minerals, antibiotics, salt, antioxidant and Vitamins.
Chapter Four
RESULTS
Physical observation
During the course of the administration, we observed that there is stimulation of appetite up to the third week of administration follow by reduction in the intake of food until the end of the administration in all the groups administered with alcohol.
DISCUSSION
In the present study, we evaluate the effect of chronic oral consumption of low dose of alcohol on the cerebrum (frontal lobe) by using neurobehavioral, biochemical, histological and morphological method.
Physical observation
During the course of the administration, it was observed that there is stimulation of appetite up to the third week of administration follow by reduction in the intake of fooduntil the end of the administration in all the groups administered with alcohol. Alcohol is the second highest source of energy, on a per gram basis, of all the macronutrients, providing 29 kJ/g (7 kcal/g) (Foster and Marriott, 2006).
Unlike other macronutrients, there is minimal evidence for any reduction in food intake to compensate for the potential energy in alcohol. In contrast, moderate alcohol consumption prior to a test meal leads to a short-term increase in food intake. This stimulatory effect of alcohol is not apparent beyond acute administration, but the inability to reduce voluntary energy intake in response to energy from alcohol metabolism is evident over extended periods. Alcohol suppresses fatty acid oxidation, increases short-term thermogenesis and stimulates a number of neurochemical and peripheral systems implicated in appetite control, including inhibitory effects on leptin, glucagon-like peptide-1, and serotonin, and enhancement of gamma-aminobutyric acid, endogenous opioids and neuropeptide Y. All of these effects could lead to overeating, and mechanisms underlying appetite stimulation through alcohol require further substantiation (Yeomans et. al., 2003).
Forsander, (1998) reported an experiments made in vitro in isolated tissue preparations and in perfused organs suggest that ethanol should be an excellent nutrient. The ethanol molecule contains much energy in which the body can utilize for its energy supply at least as efficiently as it uses the calories of ordinary food. Ethanol is a neutral water-soluble substance that requires no digestion before it is absorbed in to the blood by simple diffusion.
Chapter Six
CONCLUSION
In the present study, Histo-morphological, Biochemical and Neurobehavioral Evaluation of the frontal lobe following chronic alcohol consumption in Wistar rats. The results that chronic consumption of low dose of alcohol in Wistar rats can cause reduction in food intake, have no significant changes on body weight, improve cognitive activities in both male and female in dose dependent manner, has no effects on anxiety related behavior and violence and causes no significant changes in the production of reactive oxygen species.With respect to the findings of present result, chronic daily oral administration of lose dose of alcohol:
- improve learningand memory in male and female Wistar rats
- does not significantly increase the production of reactive oxygen species which can cause oxidative damage in male and female Wistar
- does not have a significant effect on anxiety and aggression in male and female Wistar
Recommendation
- Further studies are need to evaluate the effect of chronic administration of low dose ofalcohol on the number of Neurons and Volume of the cerebrum using stereological
- In addition, further studies are required to investigate the effects of chronic consumptionof alcohol on the mitochondrial gene expression, which is responsible for the mitohormetics effect of low dose of
Contribution to knowledge
- Chronic oral administration of alcohol at dose of 0.16g/kg and 0.24g/kg weight per daysignificantly (p <05) improvement in memory over time in male Wistar rats and at a dose of 0.12g/kg body weight per day also causes a significant improvement in memory in female Wistar rats.
- Chronic oral administration of alcohol at dose of 0.12g/kg, 0.16g/kg and 0.24g/kg bodyweight per day have no significant (p> 0.05) effect the production of reactive oxygen species in both male and female Wistar
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