拟除虫菊酯对大鼠脑组织及肝脏生物转化酶的影响

目的 实验研究溴氰菊酯（ＤＭ）和氯菊酯（ＰＭ）对大鼠脑组织及肝脏某些生物转化酶的影响。方法 应用荧光分光光度法、二硝基苯肼比色法和Ｈａｂｉｇ法检测７－乙氧基试卤灵－Ｏ－脱乙基酶９ＥＲＯＤ０、Ｂ型单胺氧化酶９ＭＡＯＢ）和谷胱甘肽Ｓ－转移酶（ＧＳＴ）活力。结果 整体实验中，ＤＭ染毒动物肝脏ＥＲＯＤ、ＭＡＯＢ活力分别下降了４７．９４％和２２．７６％；脑组织和肝脏ＧＳＴ活力分别增加了２２．２０％和３９．５     

Contrasting effects of acute and chronic ethanol administration on rat liver tyrosine aminotransferase

We compared the effects of acute and chronic ethanol administration on the activity and synthesis of tyrosine aminotransferase (TAT) in rat liver. In acute experiments, chow-fed rats received a single dose of either ethanol (6 g/kg body wt.) or saline. In chronic studies, rats were pair-fed liquid diets containing either ethanol (36% of calories) or isocaloric maltose-dextrin for 6–8 weeks. In rats acutely fed ethanol, the relative rate of TAT synthesis was more than twofold higher than in saline-treated controls. In rats subjected to chronic ethanol administration, both the TAT activity and synthesis rate were the same as in pair-fed controls, but both these parameters in the two groups were equal to those in animals given acute ethanol acutely. These findings indicate that whereas acute ethanol administration was associated with a stimulation of TAT synthesis, long-term ethanol administration was not. The data suggest that ethanol itself does not directly induce TAT. Rather, enzyme synthesis is regulated by one or more endogenous secondary effector(s) whose production is influenced differently by acute or chronic ethanol feeding.     

Effects of ethylene glycol on drug metabolizing enzymes in rat liver

We investigated the effects of ethylene glycol (EG) on the hepatic drug metabolizing enzymes. The exposed group was given 1% EG solution and the control group was provided with distilled water for 2 weeks ad libitum. The body weight of the exposed group was the same as that of the control group. The liver and kidney weight per body weight did not change. The daily drinking volume for the exposed group on the average showed an increase of 13.5% over that of the control group. Hematologically and biochemically, anemia, liver and renal dysfunction were not seen. The content of the hepatic microsomal cytochrome P-450 in the exposed group showed an increase of 17% over that of the control group, but the contents of cytochrome b5, protoheme and the activities of NADPH-cytochrome c reductase, NADH-ferricyanide reductase did not change. The activities of the hepatic cytosolic alcohol dehydrogenase and glutathione reductase, glutathione peroxidase, glutathione-S-transferase also did not change. These results indicate that the hepatic microsomal cytochrome P-450 takes part in the metabolism of EG.     

Effects of acute ethanol administration and chronic ethanol feeding on mixed function oxidation in deermice lacking ADH

Hepatic microsomes catalyze the oxidation of ethanol and other drugs. The mechanisms through which ethanol alters mixed function oxidation are still debated. There is evidence that ethanol and drugs interact at a microsomal level, but there are also claims that ethanol may interfere with drug metabolism indirectly by affecting the supply of NADPH through NADH production in the ADH pathway. To investigate the role of chronic ethanol consumption, deermice with normal liver ADH (ADH+) or genetically lacking ADH (ADH-) were pair-fed liquid diets containing ethanol or isocaloric carbohydrate for 23 days. The acute effects of ethanol were studied in deermice fed standard laboratory chow and tap water ad lib. In vivo and in vitro, the effects of an acute dose of ethanol and chronic ethanol feeding on mixed function oxidation as measured by the demethylation of aminopyrine were similar in both animal strains. Statistical analysis showed no significant differences between ADH+ and ADH- animals under all experimental conditions studied. We conclude that induction and inhibition of mixed function oxidation by ethanol may be related to the interaction of ethanol with hepatic microsomes rather than to redox changes produced by ADH mediated ethanol metabolism.     

Effects of chronic ethanol exposure on fatty acids of rat brain glycerophospholipids

The lipid composition was analysed in forebrain subcellular fractions from rats treated with ethanol for three weeks and control rats. Increased proportions of oleic acid and a decrease in palmitic acid were consistently found in total glycerophospholipid fractions after ethanol exposure. The fatty acid compositions of individual phospholipids were also significantly changed. The proportion of docosahexaenoic acid was decreased in brain phosphatidylserine. In contrast to the decrease in the degree of unsaturation in phosphatidylserine, there was an opposite change in phosphatidylcholine wherein the degree of unsaturation was increased. No changes were produced in total cholesterol or phospholipid concentrations. These results point to a high degree of complexity of the mechanisms behind ethanol-induced changes in membrane lipid composition. The decrease in unsaturation in phosphatidylserine is probably an adaptive effect in order to counteract the fluidizing effect of ethanol. There are two possible explanations for the increase in unsaturation in brain phosphatidylcholine. The change may be due to adaptation to other biophysical effects, e.g., expansion of the membrane surface or be secondary to a change in liver lipid metabolism.     

Effect of chronic ethanol administration on thiamin metabolism in the rat

The effect of chronic alcohol administration on the absorption, excretion and metabolism of thiamin in the rat has been examined. In ethanol-fed rats receiving a marginal daily intake of thiamin (10 microgram/day) by stomach tube or by intraperitoneal injection, less of the vitamin and its metabolites were excreted in the urine as compared to controls administered the same diet except that sucrose replaced the energy represented by ethanol. More of the oral dose of thiamin was excreted in the feces of the ethanol-fed as compared to control rats. These data support previous reports of decreased adsorption of thiamin from the gut in animals exposed to ethanol. The studies in which the thiamin was administered by intraperitoneal injection also indicate an effect of ethanol on thiamin excretion in the urine which appears not to be related to absorption of the vitamin from the gut. An examination reveals no difference in the level of thiamin and its metabolites in the tissues of ethanol-fed as compared to control rats receiving thiamin by stomach tube. Thus, the decreased absorption of thiamin from the gut in the ethanol-fed rats seems to be balanced by a decreased excretion in the urine leading to a comparable accumulation of the vitamin in the tissues as controls.     

Ganglioside long-chain base composition of rat brain subcellular fractions after chronic ethanol administration

Rats of two different ages (2 and 7 months) were treated with an ethanol-containing liquid diet for 24 days and changes of the ceramide composition of gangliosides were studied in the brain synaptosomal, microsomal and myelin fractions. Greater differences were observed in the younger age, where ethanol treatment caused a significant increase of C20: 1 LCB in GM1 ganglioside of synaptosomes and microsomes and in GDla of myelin.     

Effects of capsaicin and ethanol on hepatic drug-metabolizing enzymes in rat

Capsaicin (CAP; 50 mg/kg body wt., p.o.) and/or ethanol (EtOH; 10% (v/v) in the drinking water) were given for a period of 30 days to male rats, and changes in hepatic drug-metabolizing enzymes were investigated. The EtOH alone tended to increase the microsomal parameters such as cytochrome P-450 content and enzyme activities of aniline hydroxylase, aminopyrine demethylase and UDP-glucuronyl transferase, while it did not affect the cytosolic enzyme activities of sulfotransferase and glutathione S-transferase. The administration of CAP without EtOH tended to decrease all of the parameters studied. In contrast, the ingestion of CAP with EtOH tended to increase even the elevated microsomal enzyme activities by EtOH alone. These data suggest that chronic alcohol ingestion could modify the potential for detoxification of xenobiotics in persons who regularly consume a large amount of hot peppers.     

Effect of chronic ethanol administration on disposition of ethanol and its metabolites in rat.

We studied the effects of chronic alcohol intake on the disposition of alcohol and its metabolites in the rat. We used male Wistar rats for all of the experiments in this study. Using a pair-feeding process, rats were fed a liquid diet containing alcohol or without alcohol for 6 weeks. Ethanol solutions (0.5, 1.0, 1.5, and 2.0 g/kg body weight [BW]) were administered as a bolus, intravenously. We then measured blood ethanol and acetate concentrations. Simultaneous multiline fitting was performed using mean blood alcohol concentration (BAC)-time curves fitted to the one-compartment open model with parallel first-order and Michaelis-Menten elimination kinetics. At low doses (0.5, 1.0, and 1.5 g/kgBW), no differences were observed between the alcohol group and the control group with respect to ethanol elimination rate, area under the curve of ethanol (AUC(EtOH)), and mean residence time of ethanol (MRT(EtOH)). At higher doses (2.0 g/kgBW), ethanol elimination rate in the alcohol group was significantly higher than in the control group (P<.5%). These findings were also substantiated by corresponding changes in AUC(EtOH) and MRT(EtOH). At low doses, no differences were observed between the alcohol group and the control group with respect to plateau concentration of acetate (AcT) (concentration of steady state=C(ss)AcT), area under the curve of AcT (AUC(AcT)), and mean residence time of AcT (MRT(AcT)). However, at higher doses, although there were no differences in C(ss)AcT, both AUC(AcT) and MRT(AcT) were significantly lower in the alcohol group when compared to the control group (P<.5%). Chronic alcohol consumption increases ethanol oxidation and AcT metabolism in rats, as observed at high blood alcohol concentrations (BACs). These effects were observed at BACs of 3.5-4.5 mg/ml, and were not observed at lower doses. Thus, with general alcohol consumption, interindividual differences and intra-individual changes in alcohol metabolism may not take into account increased or accelerated metabolism due to alcohol tolerance.     

Influence of acute ethanol administration on hepatic glutathione metabolism in the rat

The effect of acute ethanol administration on the hepatic metabolism of glutathione was studied in male Wistar rats. Animals fasted for 18 hr received ethanol (5 g/kg body wt.) through a gastric tube as a 20% (w/v) solution in 0.154 NaCl. Four hours after administration of ethanol liver glutathione content was decreased by 21% when compared to saline-treated controls. A significant reduction (28%) was also found in gamma-glutamylcysteine synthetase activity and plasma glutathione levels were increased non significantly by 17% with respect to control rats. Glutathione S-transferase activity in the liver of ethanol-treated animals was decreased by 28% but no change was found in total glutathione peroxidase activity. The results indicate that the lowered glutathione synthesis could be an important factor contributing to the reduction of hepatic glutathione concentration following the acute ingestion of ethanol.     

Effect of ethanol administration on the in vivo kinetics of thiamine phosphorylation and dephosphorylation in different organs. I. Chronic effects

The effects of chronic ethanol administration on different steps in the metabolism of thiamine (T), thiamine mono- (TMP) and pyrophosphate (TPP) were determined in vivo in the liver, kidney, heart, skeletal muscle and small intestinal mucosa. The radioactivity of T and its phosphoesters was measured in plasma and in the selected organs under steady-state conditions and at fixed time intervals (0.25-240 hr) after an i.p. injection of Thiazole-[2-14C]-thiamine (30 micrograms: 1.25 microCi) in rats chronically (35 days) ethanol-treated (daily dose of 4.7 g kg-1 body wt by gastric gavage). Two types of controls were used: pair-fed rats treated with a sucrose solution isoenergetic with ethanol, and water-treated rats. A nutritionally adequate diet, which supplied an excess of thiamine, was given to the rats, producing a virtually steady content of thiamine compounds in the tissues. The analytical data obtained were elaborated using appropriate compartmental mathematical models, which allowed the fractional rate constants, turnover rates and turnover times to be calculated. Alterations in thiamine metabolism were modest and differed according to the organs. The most widespread modification was to facilitate the entry of T (small intestine, kidney and heart) or TMP (small intestine and kidney), while no significant change of T and TMP release was seen. Sucrose had minimal effect in both steps. Enzymatic transformations of thiamine were likewise marginally affected. A general trend toward a slower T pyrophosphorylation and a faster T phosphate dephosphorylation was observed in the small intestine, kidney, heart and liver. Skeletal muscle was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tetrahydropapaveroline in brain regions of rats after acute ethanol administration

Tetrahydropapaveroline (THP), the condensation product of dopamine, and its aldehyde, dopaldehyde, have been detected in brain regions of rats after acute ethanol administration. THP levels were determined in eight brain regions of animals that received ethanol (3.0 g/kg) by intraperitoneal injection 100 or 120 minutes before decapitation. The levels of THP in two brain regions, i.e., the midbrain and striatum, were determined at time intervals ranging from 50 to 120 minutes after ethanol administration. THP was not found in brain regions of untreated animals. However, significant levels of THP were found in pooled midbrains (0.50 pmol/g tissue) and pooled hypothalami (0.20 pmol/g tissue) of animals that received ethanol 120 minutes before decapitation. Most brain regions had detectable levels of THP 100 minutes after the animals received ethanol and the striatum contained the highest concentration of the alkaloid. The concentration of THP in striata tissue of rats at 50, 70, 90, or 100 minutes after ethanol administration were 0.33, 0.38, 0.33, and 0.33 pmol/g tissue, respectively. These results demonstrate that THP can be detected in specific brain regions of the rat after acute ethanol administration.     

Effects of chronic ethanol intake at a low dose on the rat brain dopaminergic system

The effects of 8-week ethanol treatment (3% v/v in drinking water) on the rat brain dopaminergic system were investigated. Chronic ethanol consumption induced a significant increase in the number of dopamine D₁ receptor sites in the caudate putamen. Conversely, no significant changes were observed in D₂ receptor density or affinity. Biochemical results were in agreement with behavioral data, as amphetamine-induced locomotor hyperactivity was significantly higher in ethanol-treated rats in comparison to controls. Moreover, grooming behavior in response to SKF 38393, a selective agonist of D₁ receptors was potentiated in ethanol-treated rats, whereas locomotor hyperactivity induced by LY 171555 (a selective agonist of D₂ receptors) was not affected by ethanol treatment. The results indicate that changes in dopamine receptors may occur in the central nervous system at levels of ethanol intake that do not induce tolerance or dependence.     

Effect of acute and chronic ethanol treatment on renal prostaglandins in the rat

To study the effects of ethanol on renal prostaglandins (PGs), we gave rats a dose of 3.0 g/kg body weight either as a single IP injection (acute treatment) or daily IP injections of the same dose for 23 consecutive days (chronic treatment). The availability of PG precursors was evaluated from the post mortem accumulation of PGF_2α in kidney as determined by gas chromatography—mass spectrometry, and the renal excretion of PGF_2α was measured by radioimmunoassay. Acute ethanol treatment had no dramatic effect on either tissue levels or urinary excretion rate of PGF_2α but chronic ethanol treatment significantly lowered renal PGF_2α levels. In another experiment we employed liquid ethanol diets and a pair feeding technique for 12 days to achieve tolerance and physical dependence on ethanol. The levels of PGF_2α and 6-keto PGF_1α were measured in kidney in rats killed at 2, 6, and 12 days post-treatment. The kidney levels of both prostaglandins were lowered throughout the period of chronic ethanol exposure but returned to normal within five days after withdrawal. Thus, chronic but not acute ethanol treatment leads to a depletion of the renal stores of prostaglandin precursors in the rat.     

The effect of chronic ethanol administration on lipogenesis in liver and adipose tissue in the rat

Rates of lipogenesis de novo have been studied in liver and epididymal fat pads of male rats chronically treated with ethanol. A solution of ethanol (150 ml/l) was administered as the only drinking fluid for 3 months with a standard solid diet; both food and drink were available ad lib. Lipogenesis in vivo was measured by the incorporation of tritiated water into lipid fractions: non-saponifiable lipid and fatty acids. Non-saponifiable lipid, both in liver and in adipose tissue, was unaffected by ethanol treatment. However, fatty acid synthesis de novo was significantly enhanced in both liver and adipose tissue, by 150 and 300% respectively. Plasma triacylglycerol and non-esterified fatty acid levels were unchanged and plasma glucose concentration slightly increased by ethanol administration. The rate of lipogenesis increased when insulin: glucagon increased twofold due to the effect of ethanol.     

Effects of chronic alcohol administration on lactational performance in the rat

Lactating rats, with litters adjusted to eight pups on day 2, were implanted with an atrial catheter on day 3 of lactation. Alcohol in doses of 0.0, 1.0, or 2.0 g/kg BW was infused from day 5 to 12. The blood alcohol levels (BALs) achieved following infusion of the initial doses were maintained for 4 hours daily by infusion. To control for the reduced food intake in alcohol administered groups, rats receiving alcohol doses of 0.0 and 1.0 g/kg BW were pairfed to 2.0 g/kg BW alcohol group. For infusion, combinations of 50% dextrose, 30% alcohol in saline, and saline solutions were used for 0.0 and 1.0 g/kg BW alcohol groups whereas the 2.0 g/kg BW alcohol group received 30% alcohol in saline thereby equilizing the calorie intake of the three experimental groups. On day 12, pups were separated from the dams at 0800 h, a catheter extension was attached at 0900 h and baseline blood samples for prolactin level were taken at 1000 h. Following infusion of initial alcohol doses, samples were taken for BALs. Additional samples for BALs were removed 2 h after continuing the infusion. At the end of 4-h infusion, blood samples were taken for alcohol and postinfusion prolactin levels. In groups designed to study the suckling-induced prolactin release, pups were weighed and returned to the dams. Subsequent blood samples were taken 30 min after initiation of suckling. In nonsuckled groups, blood samples were obtained at corresponding time periods. BALs were determined by head space gas chromatography and plasma prolactin by a double antibody radioimmunoassay. Suckling latency and milk consumption during the 30 min of suckling were measured. Dams' and litter weights were determined on days 2, 5, and 12 of lactation. Infusion of alcohol for 8 days from day 5 to 12 of lactation did not affect maternal body weight. However, litters nursed by dams receiving 2.0 g/kg BW alcohol weighed less on day 12 compared to all other groups. Suckling latencies did not differ among groups. Milk consumed during the 30 min of suckling was lower for the alcohol administered groups. The inhibitory effect on milk consumption was greater for the 2.0 g/kg BW group than in the 1.0 g/kg BW alcohol group. Alcohol infusion did not affect the basal prolactin, whereas, the higher dose (2.0 8/kg BW) inhibited suckling-induced prolactin release. Collectively, data from the present study demonstrate that chronic alcohol administration to lactating rats adversely affects lactation as indicated by its effect on milk yield, litter growth and suckling-induced prolactin release.     

Effects of ethanol feeding and malnutrition on collagen synthesizing and degrading enzymes in rat pancreas

This study was performed to delineate the combined effects of a low-fat diet and chronic ethanol ingestion on collagen metabolism in rat pancreas. Rats fed a very low-fat diet (5% of total calories as lipid) for 12 weeks developed malnutrition as judged by weight loss (−33% of the initial body weight) and low serum albumin and amylase levels. The pancreas of malnourished rats showed increased collagenase activity with respect to animals fed a 35% lipid diet (p < 0.05). Hydroxyproline content was higher in the pancreas of malnourished rats and collagenase activity correlated well with hydroxyproline content (r = 0.57, p = 0.0013). Ethanol feeding for 12 weeks, regardless of the nutritional state of the rats, did not change the synthesis and degradation rates of collagen in the pancreas. The present study suggests that malnutrition may have profound effects on collagen metabolism.     

Acute ethanol and acetaldehyde administration produce similar effects on L-type calcium channels in rat brain

The present study investigates the effect of acute ethanol and acetaldehyde administration on neuronal L-type calcium channels by measuring the binding of 3H-nitrendipine (3H-NTP). Acute ethanol (3 g/kg orally) transiently increases (+40% at 40 min) 3H-NTP binding. Acetaldehyde has a similar effect, but the onset of action is shorter; in fact the binding increase peaks 15 min following administration and is completely reversible within 2 hours. Disulfiram pretreatment does not modify the effect produced by acute ethanol on 3H-NTP binding. The results indicate that acetaldehyde may participate in mediating the action of ethanol on voltage sensitive L-type calcium channels with consequent alterations of neuronal excitability.