Histo-morphological, Biochemical and Neurobehavioural Evaluation of the Frontal Lobe Following Chronic Alcohol Administration in Wistar Rats
Chapter One
ย Aimย andย Objectivesย ofย the Study
ย Aimย ofย the Study
ย This study was aimed at evaluating the effect of chronic alcohol consumption on the frontal lobe of the cerebrum of adult Wistar rats
Objectivesย of theย Study
ย The objectives of the study were to evaluate the frontal lobe followingย 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
LITERATUREย REVIEW
ย Alcohol Absorption
The alcohol molecule is a small polar molecule with molecular weight of 46.068 g/mol andย densityย ofย 0.7892g/mlย havingย bothย lipophilicย andย hydrophilicย characteristicsย (Ferreiraย andย Willoughby, 2008). The amphipathic qualities of alcohol help to explain its pharmacokineticsย within the body. The lipophilic qualities explain how alcohol is absorbed by passive diffusionย across the cell membranes without the need for modification. The hydrophilic combined with theย polar properties of the alcohol molecule explain how alcohol is completely soluble in water andย thusย has aย similarย volume ofย distributionย toย totalย bodyย waterย (TBW).
Blood alcohol concentration (BAC) is determined by the various factors that affect the rateย atwhich alcohol is absorbed (including the amount and concentration of alcohol ingested and theย quantity and composition of food in the stomach),distributed, metabolized and excreted from theย body (Mumenthalerย etย al.,ย 1999). Followingย oral administration absorption andย distributionย determines the proportion and rate at which orally ingested alcohol reaches the blood and bodyย tissuesย (bioavailability).
As alcohol is a small water soluble molecule that can cross cell membranes, it is absorbed fromย both the stomach (20 %) and the upper small intestine (80 %) (Paton, 2005 and Norberg et al.,ย 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 foodย inhibits absorption because approximately 20% of theย ingested alcohol isoxidisedย beforeย itย canย be absorbed (Paton, 2005 and Norberg et al., 2003). The speed ofabsorption is also influence byย variationย inย portalย bloodย flowย becauseย alcoholย crossesย theย biologicalmembraneย byย passiveย diffusion (Paton, 2005; Ferreira and Willoughby, 2008) thus good blood flow will maintain theย concentrationย gradientย andpromoteย absorption.ย Anyย stimulationย of theย sympatheticย nervousย system (e.g. emotional state orexercise) will reduce portal blood flow and gastric motility thusย decreasing alcohol absorption. The typeof drink consumed also plays a role. Drinks with alcoholย content between 20-30% are absorbed quickest (Paton, 2005). Whereas drinks with a higherย alcohol content are absorbed more slowly, because an alcohol content over 30% irritates theย gastric mucosa increasing mucus secretion and decreasing gastric emptying. Thus, drinks with anย alcohol content above 30% can cause a faster rise in BAC if served diluted with a mixer, than ifย they are serve without dilution. This is especially true if the mixer is a carbonated drink as thisย canย alsoย increaseย the rateย ofย absorptionย (Paton,ย 2005).
Alcoholย Distribution
ย Theย bioavailability of alcohol is reducedย by firstย passย metabolism (FPM). Oxidation of alcoholย by gastric alcohol dehydrogenase (ADH) in the gastric mucosa accounts for a small proportion ofย FPM, but the majority occurs via oxidation by ADH in the liverย hepatocytes (Ferreira andย 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 tissueย (Mumenthaler, et al., 1999), but is generally achieve within 1-2 hours (Ferreira and Willoughby,ย 2008). The same amount of alcohol absorbed can affect different people in different ways (Paton,ย 2005). Differences in TBW will influence alcohol pharmacokinetics because it determines theย volumeย ofย distributionย availableย forย alcoholย distributionย withinย theย body.ย Alcoholย isย preferentially distributed in tissues with higherย waterย contents and a good blood supply (e.g.ย brainย andย skeletalย muscle).ย Bodyย compositionย isย thereforeย anย importantย considerationย inย pharmacokinetic studies (Jones, 2007) because both body size and composition will have aย significantย impactย on theย volumeย of distribution.ย Females generallyย haveย aย proportionatelyย smaller lean body mass and a smaller blood volume (Paton, 2005 and Mumenthaler, et al., 1999).ย The result is a lower volume of distribution and higher BAC when females ingest the sameย amount of alcohol as men (Mumenthaler, et al., 1999). It has also been suggested that higherย BAC may be due to lower FPM by gastric ADH in the gastric mucosa of females (Vogel-Sprott,ย 1992).ย Thisย wouldย increase theย bioavailabilityย ofย alcoholย resultingย in increasedย 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, etย al.,ย 1997).
Chapter Three
ย MATERIALSย ANDย METHOD
Experimentalย Animals
ย For the purpose of this study, thirty-two (32)apparently healthy Wistar rats of both sexes wereย obtained from the Department of Human Anatomy Bello University, Zaria. The animals wereย housed in the animals House of the Department and were acclimatized for one weeks before theย commencementย ofย theย experiment.
Allย animalsย wereย maintainedย onย standardย animalย dietย feedsย andย water.ย Theย animalsย wereย categorizedย intoย controlย andย treatmentย groups.ย Theย animalsย wereย weighedย beforeย theย commencementย ofย the experimentย andย animalsย weighedย betweenย 80ย andย 120g.
Animalย 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.
Compositionย ofย feedย includeย Crudeย proteinย (13%),ย Crudeย fibreย (8%),ย Fatย (15%),ย Calciumย (0.80%),andย phosphorusย (0.40%).Otherย constituentsย include:ย cereals,ย essentialย aminoย acids/proteins,ย vegetables,ย animalย protein,ย minerals,ย antibiotics,ย salt,ย antioxidant andย Vitamins.
Chapter Four
RESULTS
Physicalย observation
During the course of the administration, weย observed thatย there is stimulation of appetite up toย the third week of administration follow by reduction in the intake of food until the end of theย administrationย inย allย theย groups administeredย withย alcohol.
DISCUSSION
Inย the presentย study,ย weย evaluateย the effectย ofย chronicย oralย consumptionย ofย low doseย ofย alcoholย on the cerebrum (frontal lobe) by using neurobehavioral, biochemical, histological andย morphologicalย method.
Physicalย observation
During the course of the administration, it was observed that there is stimulation of appetite up toย the third week of administration follow by reduction in the intake of fooduntil the end of theย administration in all the groups administered with alcohol.ย Alcohol is the second highest sourceย of energy, on a per gram basis, of all the macronutrients, providing 29 kJ/g (7 kcal/g) (Foster andย Marriott,ย 2006).
Unlike other macronutrients, there is minimal evidence for any reduction in food intake toย compensate for the potential energy in alcohol. In contrast, moderate alcohol consumption priorย to a test meal leads to a short-term increase in food intake. This stimulatory effect of alcohol isย not apparent beyond acute administration, but the inability to reduce voluntary energy intake inย responseย toย energyย fromย alcoholย metabolismย isย evidentย overย extendedย periods.ย Alcoholย suppresses fatty acid oxidation, increases short-term thermogenesis and stimulates a number ofย neurochemical and peripheral systems implicated in appetite control, including inhibitory effectsย on leptin, glucagon-like peptide-1, andย serotonin, and enhancementย of gamma-aminobutyricย acid, endogenous opioids and neuropeptide Y. All of these effects could lead to overeating, andย mechanismsย underlyingย appetiteย stimulationย throughย alcoholย requireย furtherย substantiationย (Yeomans et.ย 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 theย frontal lobe followingย chronic alcohol consumption inย Wistar rats. The results thatย chronicย consumption of low dose of alcohol in Wistar rats can cause reduction in food intake, have noย significant changes on body weight, improve cognitive activities in both male and female in doseย dependentย manner,ย hasย noย effects on anxiety relatedย behaviorย andย violence andย causesย noย significant changes in the production of reactive oxygen species.With respect to the findings ofย presentย result,ย chronic dailyย oralย administrationย ofย loseย doseย ofย 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 theย numberย of Neurons and Volume of the cerebrum usingย stereological
- In addition, further studies are required to investigate the effects of chronic consumptionofย alcoholย onย theย mitochondrialย geneย expression,ย whichย isย responsibleย forย theย mitohormeticsย effectย ofย low doseย of
Contributionย toย 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 aย dose of 0.12g/kg body weight per day also causes a significantย improvementย in memoryย inย femaleย Wistarย 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 oxygenย speciesย inย bothย male andย femaleย Wistar
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