Morphometric features of rat pinealocytes in conditions of chronic ethanol intoxication

Ethanol has chronobiological effects, which are associated with inhibition of melatonin synthesis and secretion and disruption of the sleep-wake cycle. Ethanol is known to cause sleep fragmentation due to frequent awakenings, prolong wakefulness, and reduce the duration of the slow sleep phase. At the same time, changes in the morphology of the pineal gland under chronic exposure to ethanol remain poorly studied. Of particular interest are changes in the basic morphometric parameters of pinealocytes, because they are a marker of the functional state of the pineal gland. The aim of the study was to morphometrically study the features of morphological changes in rat pinealocytes in the physiological norm and in chronic ethanol intoxication. To achieve this goal, we used 20 laboratory male rats: a control group and an experimental group. The control group was under standard vivarium conditions. For the experimental group, alcohol intoxication was modeled by injecting a 40% ethanol solution at the rate of 12 mg/kg of body weight intragastric 4 times a day. The morphometric parameters of pinealocytes were studied on day 30 from the start of the study. According to the results of morphometric measurements, a significant increase in the parameters of light pinealocytes and a decrease in the parameters of dark cells were established. It was determined that the average values of the cytoplasm area of light pinealocytes increase by 54.55% (p<0.05), the area of the nucleus increases by 61.32% (p<0.05), and the area of the nucleolus by 32.84% (p<0.05) compared with the control group. The area of the cytoplasm of dark pinealocytes decreases by 27.2% (p<0.05), and the area of the nucleus by 37.33% (p<0.05). Changes in the ratio of light and dark pinealocytes were also noted. An increase in the number of active light cells by 8.17% was found. The detected morphometric changes indicate high functional activity of cells, which has a compensatory nature in response to apoptosis of pinealocytes.

Interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication

A sufficient number of facts testifying the importance of liver arginase and nitrogen monoxide in the life processes in the normal and pathological conditions have been accumulated to date. The aim of the study was to determine the significance of the relationship and interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication. In rat experiments using the modern physiological, biochemical research methods and a pharmacological approach, it was found that chronic ethanol intoxication leads to a decrease in the liver arginase activity and the triiodothyronine concentration. At the same time, the increase in the level of “average molecules”, NO3 – /NO2 –, the content of lipid peroxidation products in the plasma, as well as the increase in the blood toxicity degree, the activity of alanine amino transferase, aspartate amino transferase and the narcotic sleep duration were observed. Hyperthyroid rats demonstrated the increased liver arginase activity, the processes of detoxification, lipid peroxidation and body temperature while rats with the experimental hypothyroidism showed the opposite results. The liver arginase depression caused by the injection of Nω-hydroxy-nor-L-arginine (Nor-NOHA), or L-valine into the body prevents the body temperature increase and the development of characteristic changes in the detoxification and lipid peroxidation processes acted upon by exogenous triiodothyronine. Under the conditions of the liver arginase inhibition by Nor-NOHA or L-valine, the ethanol action is accompanied by a more significant inhibition of the liver detoxification function and an increase of NO3 – /NO2 – levels in blood plasma. The preliminary injection of an NG-nitro-L-arginine methyl ester inhibitor of NO-synthase into the animal’s body weakensthe toxic ethanol effect on the liver, as well asthe development of characteristic changes in the liver arginase activity, in the processes of detoxification and lipid peroxidation in rats with chronic ethanol intoxication. Apparently, the activity of liver arginase and L-arginine-NO system determines the severity of detoxification, lipid peroxidation processes and the formation of the thyroid status in the conditions of chronic alcoholization, which is important in the ethanol intoxication pathogenesis.

REMODELING OF THE DUCT SYSTEM OF THE RAT SUBMANDIBULAR SALIVARY GLANDS IN CHRONIC ETHANOL INTOXICATION

The aim: To determine the dynamics of changes in metric parameters of the duct system of rat submandibular glands in normal conditions and chronic ethanol intoxication. Materials and methods: 50 albino outbred rats were involved in the experiment. 10 animals were assigned in the control group, 40 animals – in the experimental group. Animals were sacrificed on 5, 9, 12 and 30 days by overdose of thiopental anesthesia. Pieces of the submandibular glands were embedded into epon-812 according to the conventional technique. Results: On day 5 of the experiment the lumen diameter of intercalated duct reduced by 9,15 % (р <0,05). The lumen diameter of the striated ducts was by 5,29 % significantly greater than the values in controls (р <0,05). The lumen diameter of the granular ducts reduced by 2,45 % (р <0,05). On day 30 of the experiment the height of the epithelial cells of the intercalated ducts was by 8,47 % significantly less (р <0,05), the height of the epithelial cells of the striated ducts was by 12,27 % less (р <0,05) and the height of the epithelial cells of the granular ducts was by 11,96 % less (р <0,05) than the values in controls. Conclusions: No recovery of parameters occurs by day 30 of the experiment, indicating the depletion of the secretory epithelium of the duct system, due to dystrophic changes caused by vascular disorder in the microvasculature.

PATHOMORPHOLOGICAL CHANGES IN THE LIVER IN CASE OF POISONING WITH ETHANOL

The article analyzes the data of autopsy and pathohistological examination of persons who died from ethanol poisoning against the background of various forms of alcoholic liver damage – adaptive hepatopathy (AGP), steatosis (AS), hepatitis (AG), cirrhosis (AC); assesses the morphological changes of the liver. New data on localization, character, degree of steatosis and fibrosis in liver acinuses were obtained. The results of the study can be used as additional criteria for the diagnosis of acute and chronic ethanol intoxication, which allows to objectify the expert conclusions in the production of forensic medical examination (research) of the corpse.

MORPHOMETRIC DESCRIPTION OF THE EXCHANGE SEGMENT OF MICROVASCULATURE OF RATS’ SALIVARY GLANDS IN NORMAL CONDITIONS AND CHRONIC ETHANOL INTOXICATION

Introduction: The state of the segments of the microvasculature, especially exchange one, has a significant effect on the organs’ functions. The results of it’s research can be objectified by morphometric method. The aim: to determine the dynamics of changes in metric indices of the exchange segment of microvasculature of rats’ submandibular glands in normal conditions and in chronic ethanol intoxication. Materials and methods: 45 albino rats were involved into study. Intact group (n=5) animals were administered with NaCl isotonic solution 4 times a day directly into the stomach. Experimental group (n=40) animals were administered with 40° ethanol 4 times a day directly into the stomach. Animals were sacrificed on 5, 9, 12 and 30 days by overdose of thiopental anesthesia. Lobules of submandibular glands were embedded into epon-812 according to standard procedure. Results: On day 5 of the experiment the outer diameter of the capillary wall significantly reduced (4,91±0,02 μm), that is 19,5 % less than the values in controls (р<0,05). On day 9 of the experiment it was 15,2 % lower than the value of control group (р>0,05). On day 30 of the experiment the outer capillary diameter was 8 % lower compared to controls (р<0,05). Conclusions: The early observation showed vasodilatation, confirmed by the constriction of the outer diameter and lumen diameter, accompanied by the thickening of the vascular wall under the influence of chronic ethanol intoxication. The indices did not come to normal values by the 30-th day of the experiment.

Structural and Functional Fundamentals of Alcoholic Disease

Aim. To suggest a new perspective on chronic alcohol intoxication by means of investigating the associated severe multiple organ pathology, which frequently becomes the cause of lethal outcome in patients suffering from drunkenness and alcoholism.Key points. The empirical basis of the study consisted in the analysis of autopsy results obtained from 1,115 corpses of persons having abused alcohol during their lifetime. In addition, 800 experiments on rats were carried out. As a result, a concept of alcoholic disease (AD) is proposed. AD is defined as a condition, in which chronic ethanol intoxication leads to the development of morphological changes in organs and systems: from minimal injuries of the microcirculatory pathway to a multiple organ pathology showing signs of alcoholism. AD pathogenesis is demonstrated to undergo 3 major stages, from (1) episodic alcohol intoxication, through (2) drunkenness and to (3) alcoholism. It is noted that, while the morphological changes are considered to be reversible during the first two stages, they become irreversible at the stage of alcoholism.Conclusion. It is concluded that the forms of the disease that involve the described morphological changes in organs and systems should be primarily treated by physicians, not by psychiatrists and narcology practitioners who are only capable of dealing with the psychological aspect of the problem.