Effect of chronic ethanol ingestion on zinc absorption in rat small intestine

The effect of chronic ethanol ingestion on the ability of the small intestine to absorb zinc was examined in male Sprague-Dawley rats. Six rats were fed the Lieber-Decarli liquid rat diet for 1 month during which 36% of their total calories were provided as ethanol, while their pair fed controls received these calories as carbohydrate. Zinc absorption was then examined simultaneously in duodenal and ileal segments byin vivo perfusion. Net absorption of zinc in the ileum was reduced by 16% following chronic ethanol feeding. Duodenal absorption of zinc was significantly less than in the ileum and was unaffected by chronic ethanol ingestion. These results demonstrate that chronic ethanol ingestion significantly impairs net zinc absorption in the ileum of the rat, the most active area of zinc uptake as measured byin vivo perfusion, and suggest that malabsorption of zinc may contribute to the zinc deficiency seen following chronic ethanol ingestion.     

Effect of chronic ethanol intake on lactase activity and active galactose absorption in rat small intestine.

The effects of feeding a nutritionally adequate liquid diet containing 5% ethanol to rats over a four week period on intestinal lactase activity and the kinetics of jejunal galactose absorption in vivo have been determined. Both lactase activity and the maximum capacity for active, saturable galactose absorption (Jmax) were increased significantly after chronic ethanol ingestion. In contrast, uptake of the sugar via the phlorhizin-insensitive (passive) route was unaffected by ethanol. Our results imply the presence of an increased maturity of the enterocyte population on the villus surface in response to ethanol. The relevance of this work to uptake studies in alcoholics is briefly discussed.     

Effect of chronic ethanol consumption on mucosal morphology and mitotic index in the rat small intestine

Rats were maintained 16 weeks on a well-balanced semisynthetic solid diet supplemented with ethanol which comprised 35% of total calories. A control group was pair-fed the same basic diet with sucrose replacing ethanol isocalorically. Striking changes in mucosal morphology and mitotic index were observed in the jejunum and ileum of ethanol-fed rats in comparison to pair-fed controls. Furthermore, it is significant that these changes were more pronounced in the ileum than in the jejunum. Since ethanol is almost completely absorbed in the stomach and upper intestine, under the conditions of this study, we propose that, apart from a possible topical toxic effect of ethanol, there appear to be other separate possible causes of the extensive small intestinal changes found in ethanol-fed rats. The first is that the changes are due to injurious effects of blood-borne ethanol; secondly, the changes could be a functional adaptation due to altered luminal nutrition as a consequence of the introduction of ethanol in the diet.     

Antecedent ethanol ingestion prevents postischemic P-selectin expression in murine small intestine

OBJECTIVE: Ethanol ingestion 24 h prior to ischemia and reperfusion (I/R) prevents postischemic leukocyte rolling and adhesion in postcapillary venules of the small bowel. Since I/R-induced leukocyte rolling is critically dependent on the expression of P-selectin by endothelial cells lining postcapillary venules, the authors hypothesized that antecedent ethanol consumption would attenuate postischemic expression of this adhesive ligand. METHODS: To address this postulate, P-selectin expression was evaluated using a dual radiolabeled monoclonal antibody technique in the jejunum of mice that received either distilled water vehicle or ethanol by gavage (dose) on day 1 and then were subjected to sham I/R (nonischemic controls) or I/R (20 min ischemia/60 min reperfusion) 24 h later. RESULTS: I/R was associated with a 2-fold increase in P-selectin expression relative to nonischemic controls, an effect that was largely abolished by antecedent ethanol ingestion. Exposing the bowel to adenosine deaminase or adenosine A2 receptor antagonists (DMPX or ZM241385), an NO synthase inhibitor (L-NIO) or an NO scavenger (PTIO), or an antioxidant (mercaptoproprionyl glycine) during the period of ethanol exposure on day 1 prevented the beneficial effect of ethanol to limit I/R-induced P-selectin expression, on day 2. CONCLUSIONS: The data indicate that antecedent ethanol exposure prevents postischemic P-selectin expression on day 2 by a mechanism that is triggered by adenosine A2 receptor activation and the formation of nitric oxide (NO) and reactive oxygen species (ROS) during the period of ethanol exposure on day 1.     

Effect of lithium ingestion on water and electrolyte transport in rat intestine

The effect of lithium ingestion on intestinal electrolyte and water transport was studied in adult Sprague-Dawley rats. We fed animals a lithium-supplemented diet for 1, 2, 4, or 16 wk before in vivo perfusion of the jejunum and colon. Lithium feeding did not alter jejunal transport of water, electrolytes, or glucose, However, at 4 and 16 wk (16-wk data given) the colon increased net water (168%), sodium (160%), and chloride (140%) absorptions, and the transmural potential difference (396%) as compared with control animals. In addition, the colon absorbed both bicarbonate and potassium against an unfavorable electrochemical gradient. The increased colonic sodium absorption was not associated with an increase in mucosal Na+, K+-ATPase activity. Furthermore, in lithium-fed animals deoxycorticosterone acetate stimulated mucosal Na+, K+-ATPase activity, but it did not further increase net sodium absorption. Neither jejunal nor colonic electrolyte transport was affected 24 h after being gavage-fed lithium. These results suggest that chronic lithium ingestion has a unique mechanism of action as other means of chronically increasing sodium absorption are associated with increased mucosal Na+, K+-ATPase activity.     

Beta-7 integrin controls enterocyte migration in the small intestine

AIM:To hypothesize that beta-7 integrin affects cellularmigration of both,lymphocytes and enterocytes.METHODS:The nucleoside analog Brd U was ip injected in beta-7-deficient mice(C57BL/6-Itgbtmlcgn/J)of male gender and age-matched male C57BL/J J mice(wild type)4,20,or 40 h before analysis.The total small intestine was isolated,dissected,and used for morphometrical studies.Brd U-positive epithelial cells were numbered in at least 15 hemi-crypts per duodenum,jejunum,and ileum of each animal.The outer most Brd U-positive cell(cellmax)was determined per hemi-crypt,numerically documented,and statistically analysed.RESULTS:Integrins containing the beta-7-chain were exclusively expressed on leukocytes.In the small intestinal mucosa of beta-7 integrin-deficient mice the number of intraepithelial lymphocytes was drastically decreased.Moreover,the Peyer’s patches of beta-7integrin-deficient mice appeared hypoplastic.In beta-7integrin-deficient mice the location of cellmax was found in a higher position than it was the case for the controls.The difference was already detected at 4 h after Brd U application,but significantly increased with time(40 h after Brd U injection)in all small intestinal segments investigated,i.e.,duodenum,jejunum,and ileum.Migration of small intestinal enterocytes was different between the experimental groups measured by cellmax locations.CONCLUSION:The E-cadherin beta-7 integrin pathway probably controls migration of enterocytes within the small intestinal surface lining epithelial layer.     

Acute and chronic exposure to ethanol and the electrophysiology of the brush border membrane of rat small intestine.

In this study we have investigated the effects of (a) chronic ethanol intake on glucose and galactose absorption across the rat jejunum in vivo and on the potential difference across the isolated brush border membrane (Vm) and (b) acute exposure to ethanol (4% or 8%) and acetaldehyde (0.25%) on changes in Vm associated with Na(+)-dependent galactose absorption across the jejunum and ileum. Chronic ethanol intake was associated with hyperpolarization of Vm and an enhanced galactose but not glucose transport. Acute ethanol and acetaldehyde were without effect on Vm whether or not galactose was present. We conclude that while a greater electrochemical gradient across the brush border membrane is a likely explanation for the stimulation of galactose absorption induced by ethanol feeding, factors other than changes in Vm are responsible for the inhibitory effects of acute ethanol.     

Effect of lithium ingestion on digestive and absorptive function of rat intestine

The long-term effect of lithium treatment on the digestive and absorptive function has been investigated in male albino rats. The uptake of D-glucose, amino acids and activities of cellular and brush border enzymes were evaluated after every 3 months. Significantly increased uptake was observed in 6-month lithium-treated rats. The absorptive capacity (Vmax) for D-glucose increased significantly without alteration in the Michaelis constant. Activities of cellular, brush border membrane disaccharidase, leucine aminopeptidase and Na+,K+-ATPase enzymes were significantly augmented in 6-month lithium-treated animals. The elevation in sucrase activity may be due to induction of enzyme since only Vmax was increased in lithium-treated animals. The present biochemical alterations suggest that long-term lithium ingestion stimulates the small bowel digestive and absorptive functions.     

Androgen-responsive functions of male rat liver. Effect of chronic alcohol ingestion

Many liver processes are sexually dimorphic, and in rats, testosterone is the major steroid hormone determinant of the differing patterns of hepatic function. The microsomal content of specific enzymes and the syntheses of specific proteins are dependent on serum testosterone to maintain this dimorphism. Because the liver of male rats is strikingly androgen responsive, and because chronic alcohol ingestion decreases serum testosterone, we sought to determine whether chronic alcohol feeding would alter the masculine pattern of hepatic liver function in male rats. We quantitated both the cytosolic and nuclear forms of the hepatic androgen receptor. Alcohol feeding of male rats results in a significant loss of both types of androgen receptor sites; the specific binding capacity of both cytosolic and nuclear receptor in alcohol-fed rats is reduced to about 30% of that in either isocalorically fed rats or rats fed ad libitum. This reduction in hepatic androgen receptor activity is concomitant with a 50% reduction in serum testosterone content in the alcohol-fed animals. In addition, the activities of two hepatic androgen-responsive proteins, namely a cytosolic estrogen binder and a microsomal enzyme, estrogen 2-hydroxylase, demonstrate a decrease in activity that parallels the decreases in both forms of the androgen receptor. Administration of testosterone to the alcohol-fed animals normalized both the hepatic androgen receptor and the androgen-responsive protein activities. From these results, we conclude that chronic alcohol feeding results in a decreased androgen responsiveness of the liver, a condition that most likely results from the decreased serum testosterone levels in the alcohol-fed animals.     

Prolactin and the small intestine. Effect of hyperprolactinaemia on mucosal structure in the rat.

To study the mechanism for the adaptive mucosal hyperplasia which occurs independent of luminal nutrition and pancreatico-biliary secretions in isolated Thiry-Vella segments of intestine from lactating rats, and to examine the effects of prolactin on small bowel mucosal structure in the rat, we used two models of experimental hyperprolactinaemia and compared quantitative histology and several markers of mucosal mass in jejunum and ileum from control rats and from test and lactating animals. Hyperprolactinaemia, induced by perphenazine injections (5 mg/kg/day for two or seven weeks) or transplantation of four pituitary glands from donor animals to beneath the renal capsule in the recipient, was confirmed by radioimmunoassay. Proof of its biological activity was obtained by weighing the mammary pads and by demonstrating true breast hyperplasia on histological section. Median serum prolactin levels increased from 50 ng/ml in the controls to 570 ng/ml in the perphenazine treated animals and to 600 ng/ml in the pituitary transplanted rats-levels comparable with those seen in lactation (870 ng/ml). In the lactating rats, there was striking mucosal hyperplasia of both jejunum and ileum but, despite the hyperprolactinaemia, there were no such changes in villus height, crypt depth, or in mucosal wet weight, protein, or DNA/unit length intestine in the perphenazine-injected or pituitary-transplanted animals. We conclude that prolactin is not atrophic to the intestine in rats and that hyperprolactinaemia cannot explain the intestinal adaptive changes of lactation.     

Acute exposure of small intestine to ethanol

Digestive Diseases and Sciences -     

Effect of chronic ethanol administration on iron metabolism in the rat

This study shows that the ingestion of ethanol provokes alterations in iron metabolism which may lead to iron overload. Impaired release of reticuloendothelial iron was shown by a decrease of the maximum red blood cell utilization when radioactive iron was supplied as colloidal iron. An impairment in the erythropoietic activity of ethanol-treated animals was also observed, as can be seen from the reduced plasma iron turnover and red blood cell utilization within 24 h of iron administration. A rise in marrow transit time was also observed. In ethanol-treated rats there was an increase in the amount of iron retained both in the liver and the spleen. This was observed in both sexes and also in the offspring from ethanol-treated mothers.     

Effect of acute and chronic alcohol feeding on prostaglandin E2 biosynthesis in the small intestine of the rat

The effect of acute and chronic alcohol ingestion on the PGE2 synthesis and PGE2 content in the duodenum and ileum was studied in rats. Following a single oral load of 20% alcohol (v/v; 4 g/kg body weight) the synthesis of PGE2 in isolated microsomes from both parts of the small intestine did not differ from that in control rats during the first 8 hours, but was increased significantly after 24 hours. Feeding a liquid diet containing alcohol (37% of total calories) for 1 week led to enhanced PGE2 synthesis in the duodenum. After feeding the diet for 6 and 12 weeks the rate of PGE2 synthesis was significantly reduced in the duodenum (-73% and -55%) and ileum (-34% and -45%) as compared with the control group. The PGE2 content of the tissue was not significantly changed 24 hours after the single alcohol load and after 1 week of feeding the alcohol-containing diet. However, after 6 and 12 weeks' feeding, the PGE2 content was reduced in both parts of the small intestine. The results suggest a biphasic response to alcohol of PGE2 synthesis in the small intestine. The increased rate of PGE2 synthesis in the initial phase might reflect an adaptive response to the injurious effect of alcohol which cannot be maintained after long-term ingestion of alcohol.     

Effect of chyme on mucosal enzyme levels in small intestine of the rat

Partial jejunectomies, gastrojejunostomies (with closed pylorus), and jejunal Thiry-Vella loops were made in order to elucidate the role of chyme in the control of mucosal mass and the activities of alkaline phosphatase, ATPase, and maltase in the small intestine of the rat. After partial jejunectomy, a partially reversible mucosal hyperplasia was seen in the small intestine with the exception of distal ileum. After gastrojejunostomy a similar hyperplasia took place in the jejunum and proximal ileum. In the jejunal Thiry-Vella loops a mucosal atrophy was found in 4 wk. After partial jejunectomy the activity of alkaline phosphatase decreased slowly in 4 wk in the remaining small intestine with the duodenum as an exception. ATPase activity decreased in the duodenum. Maltase activity remained unchanged during 8 postoperative wk. In gastrojejunostomized rats the activity of alkaline phosphatase and ATPase increased slowly during 12 wk in the jejunum aborally from the gastroenterostomy. A slight depression of maltase activity was observed in the operation area and a slight increase of enzyme activity was found in the middle of the small intestine. In jejunal Thiry-Vella loops the activity of alkaline phosphatase decreased, but no change of maltase activity could be observed during 4 wk. Perfusion of a loop with maltose solution did not cause any changes in the activity of alkaline phosphatase or maltase. The results indicate that after a change in chyme passage the adaptation takes place in the small intestine primarily by the change of mucosal mass, and at least some enzyme levels in the mucosal cells are remarkably stable.     

Effects of chronic ethanol ingestion and folate deficiency on the activity of 10-formyltetrahydrofolate dehydrogenase in rat liver

BACKGROUND: We recently observed that ethanol feeding impairs 10-formyltetrahydrofolate (10-FTHF) dehydrogenase (EC 1.5.1.6.) and 10-FTHF hydrolase activity in rats. In the present study, we explored the effects of folate deficiency or sufficiency combined with alcoholic intake on 10-FTHF and possible mechanisms by which chronic ethanol ingestion produces folate deficiency. METHODS: Sprague-Dawley rats were fed either folate-sufficient (FS) or folate-deficient (FD) diets; with or without ethanol (E) for four weeks. Hepatic 10-FTHF dehydrogenase and hydrolase activity, plasma folate and homocysteine were measured at baseline and after feeding experimental diets. RESULTS: Liver weight increased slightly with either folate deficiency or ethanol consumption. In rats fed the folate-sufficient diet with ethanol (FSE), plasma folate was decreased slightly (p<0.05) and plasma homocysteine elevated compared to rats fed the FS diet without ethanol. Ethanol did not affect plasma folate and plasma homocysteine in FD rats. Red-blood cell (RBC) folate was increased similarly in rats by ethanol feeding (FSE and FDE>FS and FD). Feeding folate deficient or ethanol (FSE, FD and FDE) diets depressed hepatic activities of 10-FTHF dehydrogenase, which catalyzes the oxidative deformylation of 10-FTHF to tetrahydrofolate (THF) and carbon dioxide. Rats consuming the FDE diet had the lowest enzyme activities of the experimental groups, implying that folate deficiency and ethanol consumption each affect enzyme activity. CONCLUSIONS: We confirm that ethanol decreases hepatic 10-FTHF dehydrogenase activity and show that this decrease occurs irrespective of folate status. This shows that modulation of 10-FTHF is one possible mechanism by which ethanol intake decreases folate status and affects one-carbon metabolism.     

Acute ethanol dosage reduces the synthesis of smooth muscle contractile proteins in the small intestine of the rat.

The effects of an acute dose of ethanol (75 mmol/kg body weight; ip) on protein synthesis were investigated in the small intestine of the rat (n = 6). Control rats (n = 6) were injected with isovolumetric 0.15 mol/l NaCl, ip. After 2.5 h, fractional rates of protein synthesis (defined as the percentage of tissue protein renewed each day by synthesis and RNA efficiencies (defined as the amount of protein synthesised per unit RNA) were measured with a large flooding dose (0.3 Ci/mol; 150 mmol/l; 150 mumol/100 g body weight; iv) of [4(3)H]-phenylalanine. Rats were killed 10 minutes after injection of the isotope and portions of the small intestine were rapidly dissected and frozen. Tissues and plasma were processed for phenylalanine specific radioactivities to obtain fractional rates of protein synthesis or protein synthesis rates relative to RNA. Rates of protein synthesis in mixed tissue proteins fell approximately 15-25% (p ranged from less than 0.005 to greater than 0.05), in response to acute ethanol dosage. The decrease in the synthesis rates of the cytoplasmic protein fraction was similar (p less than 0.025). Proteins extracted from the smooth muscle contractile apparatus, however, showed a greater response to ethanol--that is, 40-50% inhibition in protein synthesis (p less than 0.001). It is therefore possible that the functional disturbances in the ethanol-exposed gut may be because of changes in smooth muscle protein turnover with decreased amounts of contractile apparatus.     

Alcohol and absorption from the small intestine. 2. Effect of ethanol on ATP and ATPase activities in guinea-pig jejunum.

After the exposure of isolated segments of guinea-pig jejunum to 2% ethanol for one hour, a significant reduction (P less than 0-001) in the adenosine triphosphate content (ATP) was observed when compared with levels found in segments perfused with Krebs' solution. However, no alteration was noted in the activity of adenosine triphosphatase (ATPase). The chronic administration of 50% ethanol in a dose of 2-5 g/kg for two weeks did not affect either the ATP content or ATPase activity in jejunal mucosa.