Kinetics of oral propylene glycol-induced acute hyperlactatemia

The kinetics of PD-induced HL in rat have been investigated. The data obtained indicated that PD was solely responsible for the elevation (1.83- to 4.01-fold) of blood lactate that was sustained long enough to affect considerably the normal physiological function of the system. The production of lactate increased as the dose of PD increased up to 38.66 mmole/kg, thereby obeying the Michaelis-Menten kinetics model that gave an apparent Km and Vmax as 7.14 mmole/kg and 7.50 mmole/liter/hr, respectively. The t1/2 elimination time ranged from 1.40 to 5.82 hr which followed apparent first-order kinetics. Pyrazole inhibited (Ki = 6 mumole/kg) the PD-induced HL competitively, suggesting that alcohol dehydrogenase might have played a regulatory role in the conversion of PD to lactate. The PD-induced HL in rat and the LA in human patients are two distinct biochemical entities; reasoning has been given to substantiate that HL is lower order LA. Evidence has been presented to show that PD is a suitable and effective potential agent for producing experimental HL in rat in preference to agents that are currently being used.     

In vivo ethanol elimination in man, monkey and rat: a lack of relationship between the ethanol metabolism and the hepatic activities of alcohol and aldehyde dehydrogenases

The in vivo ethanol elimination in human subjects, monkeys and rats was investigated after an oral ethanol dosage. After 0.4 g. ethanol/kg of body weight, ethanol elimination was much slower in human subjects than in monkeys. In order to detect a rise in monkey plasma ethanol concentrations as early as observed in human subjects, ethanol had to be administered at a dose of 3 g/kg body weight. Ethanol metabolism in rats was also much faster than in human subjects. However, human liver showed higher alcohol dehydrogenase activity and higher low Km aldehyde dehydrogenase activity than rat liver. Thus, our data suggest a lack of relationship between hepatic ethanol-metabolizing activities and the in vivo ethanol elimination rate.     

Acute cytogenetic effects of tyramine, MTCAs, NaCl and soy sauce on rat bone marrow cells in vivo

The acute cytogenetic effects of tyramine and MTCAs, precursors of the mutagen present in soy sauce, were studied with the in vivo chromosome aberration test in rat bone marrow cells. The chemicals were administered intraperitoneally. Statistically significant positive results were obtained with tyramine at a dose of 5 mmole/kg (686 mg/kg) body weight and with MTCAs at doses over 0.50 mmole/kg (115 mg/kg) body weight, respectively. Chromosome aberrations (CA) induced by L-proline co-administered with either tyramine or MTCAs were significantly lower than those induced by each chemical alone. These data suggest that L-proline, after endogenous nitrosation, became nitrosoproline and suppressed CA, and that, as a result of in vivo nitrosation of tyramine and MTCAs, they became mutagenic nitroso compounds showing positive results. Statistically significant positive results were obtained by administration of 40 mmole NaCl/kg body weight (2338 mg/kg). The cocarcinogenic role of NaCl with tyramine was suggested because soy sauce contains about 18% NaCl.     

Effect of ethanol upon isoproterentol stimulation of growth and secretion in the mouse parotid gland

Isoproterenol (0.3 mmole/kg body wt.), when injected into the mouse intraperitoneally, increases the weight by 35% and stimulates DNA synthesis 30-fold in the parotid gland. The induction of both hypertrophy and hyperplasia is completely inhibited by ethanol at a dose of 200 mmole/kg body wt. but is almost unaffected by 60 mmole/kg. The full inhibiton of both growth parameters is observed when ethanol is administered up to 5 hr after isoproterenol. Partial inhibition is observed when ethanol is given as long as 15 hr after isoproterenol. It contrast ethanol did not alter the secretion of α-amylase in response to isoproterenol. Ethanol had no effect upon the rise in cyclic GMP level caused by isoproterenol but augmented the rise in cyclic GMP In agreement with these $\text{in}$$\text{vivo}$ observations, low concentrations of ethanol activated adenylate cyclase $\text{in}$$\text{vitro}$, however guanylate cyclase activity was quite strongly inhibited. Although high levels of ethanol (300 mmole/kg) inhibited the induction of both ornithine decarboxylase and S-adenosylmethionine decarboxylase little inhibition was seen at 200 mmole/kg suggesting that the interference with polyamine metabolism is not the mechanism of the ethanol effect upon isoproterenol-induced parotid growth.     

Treatment of acute cobalt intoxication in rats with L-methionine

The antidotal action of L-methionine in acute cobalt (II) chloride intoxication given orally or intraperitoneally to rats has been investigated in this paper. The doses of CoCl2 (2.73 mmole/kg oral, 0.21 mmole/kg i.p.) are always above their LD50 for both means of administration, reaching during oral administration values above its LD95 (4.20 mmole/kg). The doses of L-methionine varied from 0.63 mmole/kg (i.p.) to 8.19 mmole/kg (orally). L-methionine did not show a significant antidotal action (mortality rates) against the other sulphurous aminoacid: L-cysteine, which is considered an effective antidote. The administration of Co2+-methionine chelates prepared in vitro, showed rates of 10% mortality when given orally and 30% when given intraperitoneally, against Co2+-cysteine and co2+-N-acetylcysteine chelates with rates of 0% mortality. No significant functional changes were observed in the survivors killed seven days after administration in groups receiving L-methionine. Although L-methionine cannot be considered an effective antidote, it is likely to reduce partially the toxic effects of cobalt.     

Calcium distribution and exchange in the rat uterus

The calcium content and distribution of the rat uterus were determined employing flame photometry and Ca⁴⁵ determinations. The total uterine calcium concentration was found to be 2.25 millimoles (mmoles) per kilogram wet weight, 0.45 of which was inexchangeable. The exchangeable Ca could be divided into 0.8 mmole/kg wet weight extracellular and 1.0 mmole/kg wet weight intracellular. The concentration of ionic Ca in rat serum was obtained by equilibrium dialysis as 1.5 mM or 53 % of the total serum Ca. The observed Ca distribution required that its active transport be postulated, since the membrane was shown to be permeable to Ca and the internal Ca concentration was far below its electrochemical equilibrium value. Metabolic inhibition by iodoacetate or dinitrophenol caused a net Ca uptake, but cooling to 4°C and ouabain did not. Iodoacetate did not affect the Ca⁴⁵ efflux, but did increase the influx, suggesting that active Ca transport is accomplished by an exclusion mechanism. In experiments with varied external sodium concentrations, no evidence was obtained that sodium competes with calcium for inward transport. Cellular Ca binding was measured under conditions of prolonged metabolic inhibition, which abolished both active transport and the membrane potential. The association constants obtained were compatible with intracellular Ca binding to proteins, but insufficient to account for the low level of intracellular ionic Ca believed essential for relaxation. Hence metabolically dependent intracellular Ca binding was postulated. The Ca⁴⁵ efflux was slowed down by Ca-free efflux media. The presence of Sr or EDTA could completely prevent this decrease in efflux rate, and Ba could partly prevent it. Changes in Mg and Na concentration did not affect the rate of Ca⁴⁵ efflux. A model to explain Ca exchange across smooth muscle membranes has been proposed.     

Teratogenic effects of aliphatic nitriles

Intraperitoneal injection of acrylonitrile at 1.51-2.26 mmole/kg (80-120 mg/kg) or propionitrile at 0.54-1.51 mmole/kg (30-83 mg/kg) on the morning of Day 8 of gestation in the hamster induced exencephaly, encephalocoeles, and rib fusions and bifurcations in the offspring. These doses of the aliphatic nitriles also resulted in obvious toxicity to the dams. Multiple intraperitoneal injections of sodium thiosulfate at 4.03 mmole/kg (1 gm/kg) protected both dams and embryos against toxicity. When the larger doses of either acrylonitrile or propionitrile were given in the presence of sodium thiosulfate, teratogenic effects were observed in the absence of overt signs of maternal poisoning. A survey of the literature describes many studies which demonstrate that acrylonitrile and propionitrile are converted in vivo to toxicologically significant concentrations of cyanide and that sodium thiosulfate, an established cyanide antagonist, can provide protective actions against poisoning by either acrylonitrile or propionitrile. The observations suggest that the teratogenic effects of both acrylonitrile and propionitrile are related to the metabolic release of cyanide.     

Chromosome damage in the bone marrow of mice treated with the methylating agents methyl methanesulphonate and N-methyl-N-nitrosourea in the presence or absence of caffeine, and its relationship with thymoma induction.

A single dose (0.8 mmole/kg) of N-methyl-N-nitrosourea (MNUA) causes significantly more chromosome damage in the bone marrow of mice than a dose of equal toxicity to the animals, (1.1 mmole/kg) of methyl methanesulphonate (MMS) 6, 24 and 48 h after treatment. At these doses both agents alkylate bone-marrow DNA to similar extents, but only MNUA induces thymic lymphomata. The greater chromosome-damaging effects of MNUA are ascribed to the known differences in the pattern of DNA alkylation by each agent, in particular the much higher levels of O-6 methylguanine and phosphotriesters produced by MNUA. The greater chromosome-damaging effect of MNUA may account for its higher toxicity to the bone marrow which in turn may be a significant factor in the induction of thymomata. The enhancement by caffeine of chromosome damage seen particularly 48 h after MMS-treatment suggests that post-replication repair protects cells from the effects of DNA-methylation in vivo.     

Acute cytogenetic effects of tyramine and MTCAs on mouse bone marrow cells in vivo by the micronucleus test

We studied the acute cytogenetic effects of tyramine and MTCAs--precursors of the mutagen present in soy sauce--on mouse bone marrow cells in vivo by the micronucleus test. The incidence of MNPCE in bone marrow cells gradually increased and reached a maximum level 24 h after intraperitoneal injection of tyramine or MTCAs and decreased within 36 h. A dose-dependent increase in MNPCE was clearly observed for both compounds. Compared to the values for the untreated control, significant positive results were obtained with 0.5 mmole tyramine/kg (68.5 mg/kg) and with 0.1 mmole MTCAs/kg (23 mg/kg) 24 h after intraperitoneal administrations. Micronuclei were significantly induced but no severe reduction in the ratio of PCEs/NCEs was observed.     

Stereoselective metabolism of dexrazoxane (ICRF-187) and levrazoxane (ICRF-186)

A chiral HPLC method has been developed to separate razoxane (ICRF-159) in blood plasma into its enantiomers dexrazoxane (ICRF-187) and levrazoxane (ICRF-186). Dexrazoxane is clinically used as a doxorubicin cardioprotective agent and little is known of its in vivo metabolism. After intravenous administration of 20 mg/kg of razoxane to rats, the razoxane was eliminated from the plasma with a half-time of approximately 20 min. The levrazoxane:dexrazoxane ratio continuously increased with time to a value of 1.5 at 150 min, indicating that dexrazoxane is metabolized faster than levrazoxane. These results, confirmed with studies on liver supernatants, are consistent with the hypothesis that dihydropyrimidine amidohydrolase in the liver and kidney is responsible for the preferential metabolism of dexrazoxane in the rat compared to levrazoxane. It is possible that on a dose-per-dose basis marginally higher therapeutic levels of levrazoxane might be achieved in the heart tissue for a longer time compared to dexrazoxane due to dihydropyrimidine amidohydrolase-based metabolism in the liver and kidney. However, given the relatively small difference in elimination of the two enantiomers, it would be difficult to predict from this study whether or not dexrazoxane or levrazoxane might be more efficacious in reducing cardiotoxicity.     

Inhibition of ethanol metabolism by fructose in alcohol dehydrogenase-deficient deer mice in vivo

The purpose of this work was to compare the roles of a newly described mitochondrial dehydrogenase and catalase in ethanol elimination in deer mice deficient in alcohol dehydrogenase (ADH-). Fructose was used because of its well-known ability to stimulate dehydrogenase-dependent ethanol metabolism. Rates of ethanol metabolism in vivo were decreased significantly by about 60% in a dose-dependent manner by fructose in deer mice fed an ethanol-containing or a corn oil control diet. In addition, rates of metabolism of methanol, a selective substrate for catalase in rodents, were similar to rates of ethanol elimination and were decreased from 6.9 +/- 1.0 to 1.7 +/- 0.5 mmol/kg/h by fructose, supporting the hypothesis that catalase and not a mitochondrial dehydrogenase predominates in ethanol oxidation in ADH-deer mice. Glycolate, a substrate for peroxisomal H2O2 generation, reversed the inhibition of alcohol metabolism by fructose completely, indicating that fructose did not inhibit catalase directly. As expected, the ATP/ADP ratio was decreased by fructose significantly from 4.2 +/- 0.4 to 2.4 +/- 0.4 in deer mouse livers. These data are consistent with the hypothesis that fructose decreases catalase-dependent ethanol metabolism in vivo by inhibiting hepatic H2O2 generation.     

Dose-dependent inhibition of cyclosporine metabolism in mice by fluconazole

Fluconazole, a potent bis-triazole antimycotic drug, has been demonstrated to inhibit antipyrine metabolism, a cytochrome P-450 dependent process, in vivo in mice. Cyclosporine is metabolized by the cytochrome P-450 enzyme system in both mice and man. We investigated whether fluconazole had any effects on the metabolism of cyclosporine in vivo in mice. The effects of three different doses of fluconazole (1, 5, and 20 mg/kg) on the metabolism of cyclosporine in CD-1 mice were studied in single-dose experiments. Fluconazole produced significant dose-dependent decreases in the elimination rate constant and increases in the terminal half-life of cyclosporine. The 1 mg/kg dose caused a 26% prolongation of the terminal half-life and the 5 and 20 mg/kg dose prolonged the half-life by 72 and 187%, respectively. Fluconazole doses in the 1-5 mg/kg range are effective in mouse models of fungal infections. These results provide further in vivo evidence that fluconazole is a potent inhibitor of the cytochrome P-450 dependent enzyme system in mice. Future experimental studies in animals and humans are needed to evaluate possible metabolic drug-drug interactions involving fluconazole.     

Redox potential dependence of photophosphorylation and electron transfer in continuous illumination of Rhodopseudomonas sphaeroides chromatophores

The rate of ethanol elimination in fed and fasted rats can be predicted based on the liver content of alcohol dehydrogenase (EC 1.1.1.1), the steady-state rate equation, and the concentrations of substrates and products in liver during ethanol metabolism. The specific activity, kinetic constants, and multiplicity of enzyme forms are similar in fed and fasted rats, although the liver content of alcohol dehydrogenase falls 40% with fasting. The two major forms of the enzyme were separated and found to have very similar kinetic properties. The rat alcohol dehydrogenase is subject to substrate inhibition by ethanol at concentrations above 10 mM and follows a Theorell-Chance mechanism. The steady-state rate equation for this mechanism predicts that the in vivo activity of the enzyme is limited by NADH product inhibition at low ethanol concentrations and by both NADH inhibition and substrate inhibition at high ethanol concentrations. When the steady-state rate equation and the measured concentrations of substrates and products in freeze-clamped liver of fed and fasted rats metabolizing alcohol are employed to calculate alcohol oxidation rates, the values agree very well with the actual rates of ethanol elimination determined in vivo.     

Parathion and methyl parathion toxicity and metabolism in piperonyl butoxide and diethyl maleate pretreated mice

Pretreatment of male mice with piperonyl butoxide, 400 mg/kg 1 h before challenge with insecticides, resulted in a 40-fold antagonism of the acute i.p. toxicity of methyl parathion but potentiated the toxicity of parathion two-fold. Piperonyl butoxide had no effect on the toxicity of the oxygen analogs of these insecticides, methyl paraoxon and paraoxon. Diethyl maleate (1 ml/kg) depleted liver glutathione by 80% after one hour, potentiated the toxicity of both methyl parathion and methyl paraoxon, and partially counteracted the protective effect of piperonyl butoxide on methyl parathion toxicity. Piperonyl butoxide delayed the onset of brain cholinesterase inhibition by parathion. Studies of the metabolism of the insecticides by liver homogenates in vitro demonstrated that piperonyl butoxide inhibited both the oxidative formation of the oxygen analogs (activation) and oxidative cleavage to p-nitrophenol and dialkylphosphorothioic acid (detoxification). While parathion metabolism was mostly oxidative, methyl parathion metabolism appeared to be predominantly via glutathione-dependent enzymes. Studies of in vitro distribution of the insecticides demonstrated that piperonyl butoxide pretreatment resulted in elevated tissue concentrations of parathion and methyl parathion; however, the rate constant for elimination from plasma for both insecticides was unaffected by piperonyl butoxide. The overall rate of metabolism of methyl parathion in vivo was approximately twice that of parathion. These results suggest that during piperonyl butoxide inhibition of oxidative activation and cleavage, methyl parathion detoxification continues through uninhibited glutathione-dependent pathways of metabolism. The net result is a reduction in the acute toxicity of methyl parathion. Lack of an effective alternate pathway of detoxification may explain the delayed but greater toxicity of parathion in piperonyl butoxide pretreated mice.     

Ethanol metabolism in guinea pig: In vivo ethanol elimination,alcohol dehydrogenase distribution,and subcellular localization of acetaldehyde dehydrogenase in liver

Guinea pig ethanol metabolism as well as distribution and activities of ethanol metabolizing enzymes were studied. Alcohol dehydrogenase (ADH; EC 1.1.1.1) is almost exclusively present in liver except for minor activities in the cecum. All other organ tissues tested (skeletal muscle, heart, brain, stomach, and testes) contained only negligible enzyme activities. In fed livers, ADH could only be demonstrated in the cytosolic fraction (2.94 μmol/g liver/min at 38 °C) and its apparent K_m value of 0.42 mm for ethanol as substrate is similar to the average K_m of the human enzymes. Acetaldehyde dehydrogenase (ALDH; EC 1.2.1.3) of guinea pig liver was measured at low (0.05 mm) and high (10 mm) acetaldehyde concentrations and its subcellular localization was found to be mainly mitochondrial. The total acetaldehyde activity in liver amounts to 3.56 μmol/g/ min. Fed and fasted animals showed similar zero-order alcohol elimination rates after intraperitoneal injection of 1.7 or 3.0 g ethanol/kg body wt. The ethanol elimination rate of fed animals after 1.7 g ethanol/kg body wt (2.59 μmol/g liver/min) was inhibited by 80% after intraperitoneal injection of 4-methylpyrazole. Average ethanol elimination rates in vivo after 1.7 g/kg ethanol commanded only 88% of the totally available ADH activity in fed guinea pig livers. Catalase (EC 1.11.1.6), an enzyme previously implicated in ethanol metabolism, is of 3.4-fold higher activity in guinea pig (10,400 U/g liver) than in rat livers (3,100 U/g liver), but 98% inhibition by 3-amino-1,2,4-triazole did not significantly alter ethanol elimination rates. After ethanol injection, fed and fasted guinea pigs reacted with prolonged hyperglycemia.     

Metabolic Changes Detected by Ex Vivo High Resolution 1H NMR Spectroscopy in the Striatum of 6-OHDA-Induced Parkinson’s Rat

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons; however, its crucial mechanism of the metabolic changes of neurotransmitters remains ambiguous. The pathological mechanism of PD might involve cerebral metabolism perturbations. In this study, ex vivo proton nuclear magnetic resonance (¹H NMR) was used to determine the level changes of 13 metabolites in the bilateral striatum of 6-hydroxydopamine (6-OHDA)-induced PD rats. The results showed that, in the right striatum of 6-OHDA-induced PD rats, increased levels of glutamate (Glu) and γ-aminobutyric acid (GABA) concomitantly with decreased level of glutamine (Gln) were observed compared to the control. Whereas, in the left striatum of 6-OHDA-induced PD rats, increased level of Glu with decreased level of GABA and unchanged Gln were observed. Other cerebral metabolites including lactate, alanine, creatine, succinate, taurine, and glycine were also found to have some perturbations. The observed metabolic changes for Glu, Gln, and GABA are mostly likely the result of a shift in the steady-state equilibrium of the Gln-Glu-GABA metabolic cycle between astrocytes and neurons. The altered Gln and GABA levels are most likely as a strategy to protect neurons from Glu excitotoxic injury after striatal dopamine depletion. Changes in energy metabolism and tricarboxylic acid cycle might be involved in the pathogenesis of PD.     

DISTRIBUTION AND TURNOVER RATE OF VANILLYL-MANDELIC ACID AND 3-METHOXY- 4- HYDROXYPHENYLGLYCOL IN RAT BRAIN

Abstract— Vanillylmandelic acid (VMA) and 3-methoxy-4- hydroxyphenylglycol (MHPG) were measured in rat brain by a mass fragmentographic procedure. The concentration of VMA and MHPG in whole brain is 11 and 533 pmol/g, respectively. Both compounds were found in all areas of brain studied with VMA, as a percentage of both metabolites, ranging between about 1 and 8%. From the decline of the compounds after pargyline. 75 mg/kg i.p., we calculated that the rate of formation of VMA is 15 and for MHPG 202 pmol/g per h. The fractional rate of elimination of VMA and MHPG is 1.4 and 0.38 h⁻¹, respectively. The rapid rate of loss of VMA suggests that it is transported from brain. However, we were unable to block the elimination of VMA from brain by treatment with probenecid. In contrast, the elimination of MHPG could be blocked by treatment with probenecid. Our study adds support to the notion that MHPG is a major whereas VMA is a minor product of norepinephrine metabolism in brain.     

Reincorporated plasma membrane Ca2+-ATPase can mediate B-Type Ca2+ channels observed in native membrane of human red blood cells

Recently, we reported indirect evidence that plasma membrane Ca2+-ATPase (PMCA) can mediate B-type Ca2+ channels of cardiac myocytes. In the present study, in order to bring more direct evidence, purified PMCA from human red blood cells (RBC) was reconstituted into giant azolectin liposomes amenable to the patch-clamp technique. Purified RBC PMCA was used because it is available pure in larger quantity than cardiac PMCA. The presence of B-type Ca2+ channels was first investigated in native membranes of human RBC. They were detected and share the characteristics of cardiac myocytes. They spontaneously appeared in scarce short bursts of activity, they were activated by chlorpromazine (CPZ) with an EC50 of 149 mmole/l or 1 mmole/l vanadate, and then switched off by 10 mmole/l eosin or dose-dependently blocked by 1-5 mmole/l ATP. Independent of membrane potential, the channel gating exhibited complex patterns of many conductance levels, with three most often observed conductance levels of 22, 47 and 80 pS. The activation by vanadate suggests that these channels could play a role in the influx of extracellular Ca2+ involved in the vanadate-induced Gardos effect. In PMCA-reconstituted proteoliposomes, nearly half of the ATPase activity was retained and clear "channel-like" openings of Ba2+- or Ca2+-conducting channels were detected. Channel activity could be spontaneously present, lasting the patch lifetime or, when previously quiescent, activity could be induced by application of 50 mmole/l CPZ only in presence of 25 U/ml calmodulin (CaM), or by application of 1 mmole/l vanadate alone. Eosin (10 mmole/l) and ATP (5 mmole/l) significantly reduced spontaneous activity. Channel gating characteristics were similar to those of RBC, with main conductance levels of 21, 40 and 72 pS. The lack of direct activation by CPZ alone might be attributed to a purification-induced modification or absence of unidentified regulatory component(s) of PMCA. Despite a few differences in results between RBC and reincorporated PMCA, most probably attributable to the decrease in ATPase activity following the procedure of reincorporation, the present experimental conditions appear to reveal a channel-mode of the PMCA that shares many similarities with the B-type Ca2+ channel.     

Effects of oolong tea on metabolism of plasma fat in mice under restraint stress

We investigated the effects of oolong tea on the basic metabolism of plasma lipids in mice under restraint stress. When a lipid emulsion (Intralipid 20%; a lipid emulsion containing 20% soybean oil) was injected intravenously into mice, the restraint stress prolonged the half-life (T 1/2) of elimination for plasma triglyceride (TG) from 28.7 to 55.5 min. The elimination rate per minute was 48.2% in stressed mice with the rate in starved control mice as 100%. Therefore, TG metabolism was disrupted by the stress, and the use of TG as an energy source decreased. We found that the metabolism of lipids significantly response to the restrained stress in the present study. Plasma TG was 515.9 +/- 29.9mg/dl 35min after Intralipid administration in control stressed mice, 478.7 +/- 26.7 mg/dl in the stressed group given caffeine 100 mg/kg of body weight, and 418.3 +/- 18.4 mg/dl in the stressed group given 1,000 mg/kg oolong tea, an improvement by 7.2% and 18.9%, respectively, with the value for the untreated control group. The intake of oolong tea alleviated the stress-induced decrease in the rate of blood lipid metabolism; this effect may have arisen from some non-specific stress-relieving property of the tea or from acceleration of lipid metabolism by properties of polyphenols, etc. in tea. Oolong tea had anti-stress effects on plasma TG metabolism, and the effects did not depend on caffeine.     

人肝刺激因子对实验性急性肝功能衰竭小鼠的保护作用

取健康孕妇水囊引产的4～6个月龄的胎儿肝脏,按LaBreque法提取肝刺激因子(hHSS)。将hHSS注入肝部分切除的大鼠体内,用~3H-TdR掺入肝DNA测定其生物学活性。给昆明种小鼠腹腔注射D-半乳糖胺(D-Gal)以造成急性肝功能衰竭,观察hHSS对这种急性肝衰的保护效应,结果如下:①hHSS明显降低D-Gal所致的小鼠死亡率(P<0.01);②hHSS显著降低D-Gal所致sGPT和sGOT水平增高(sGPT 208.2±26.1比103.6±21.2 U/100ml;sGOT 502.6±65.4比287.8±39.4 U/100m1);③hHSS明显降低D-Gal所致的小鼠肝组织丙二醛水平增高(330.4±38.9比115.5±43.8nmol/100mg蛋白质);④光镜和电镜的组织学观察表明hHSS明显减轻D-Gal对肝组织的损害。上述实验结果表明,hHSS对D-Gal所致的急性肝衰具有明显的保护作用,其机制可能是保护肝细胞正常代谢和防止膜脂质过氧化。