Administration Of Cysteine Research Articles

Protective effect of tryptophan and cysteine against carbon tetrachloride-induced liver injury

The effects of the administration of tryptophan and/or cysteine on carbon tetrachloride (CCl 4)-induced hepatic injury were investigated. Rats received CCl 4 (1 ml/kg ip) followed 6 hr later by tryptophan (300 mg/kg) and/or cysteine (950 mg/kg) via stomach tube and rats were killed after 24 hr. Treatment with tryptophan, cysteine, or both reduced the degree of hepatic necrosis observed histologically. While CCl 4 caused polyribosomal disaggregation and decreased [ 14C]leucine incorporation into liver proteins in vitro and in vivo, treatment with tryptophan, cysteine, or both caused a shift in polyribosomes toward heavier aggregation and protein synthesis was increased. Serum activities of lactic dehydrogenase (LDH), glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and γ-glutamyl-transpeptidase were markedly increased after CCl 4 alone but after subsequent treatment with cysteine or with tryptophan and cysteine appreciable decreases occurred. Glutathione concentration decreased but total amount remained constant in the livers of CCl 4-treated rats while subsequent treatment with cysteine alone or together with tryptophan elevated both levels of glutathione. Using isolated hepatocytes, CCl 4 caused decreases in cell viability, in release of LDH, and in [ 14C]leucine incorporation into protein. Treatment with CCl 4 and tryptophan and/or cysteine revealed that cysteine alone or with tryptophan improved cell viability and decreased LDH release of the cells, while tryptophan alone or with cysteine improved protein synthesis. Upon cytologic evaluation, the isolated hepatocytes revealed membrane distortions after CCl 4 alone but these were less marked after CCl 4 plus tryptophan, cysteine, or both (most improvement). Thus, tryptophan and cysteine act in a beneficial manner against CCl 4-induced hepatic injury in the rat.

The involvement of collagenolysis in ovulation in the rat.

Collagenolytic activity in ovarian follicles was previously demonstrated by using synthetic peptides and reconstituted collagen fibers. However, attempts to demonstrate degradation of ovarian collagen and to correlate collagenase activity with ovulation were not successful. By administration of L-(5-3H) proline, we have labeled ovarian and follicular collagen and followed collagenolytic activity by separation of 3H-hydroxyproline (3H-Hyp) from acid hydrolyzates of ovarian tissue by HPLC. The level of ovarian and follicular 3H-Hyp decreased by about 40% on the afternoon of proestrus or after exogenous stimulation of ovulation by human CG (hCG), and this decrease was abolished by blocking the surge of gonadotropins with Nembutal. To verify that the observed reduction in 3H-Hyp was due to the action of a typical collagenase, the collagenous fraction was prepared from ovarian tissue and from preovulatory follicles before and after the ovulatory stimulus. The extracts were treated with trypsin (25 min, 25 C, 0.01 mg/ml) plasmin and p-amino-phenyl-mercuric acetate to fully activate the collagenase extracted along with collagen. Both, enzymatic and chemical activation of collagenase in vitro resulted in degradation of collagen. This degradation could be inhibited by cysteine and EDTA; both are classic inhibitors of mammalian collagenases. The activity of ovarian collagenase increased within 3 h after hCG-stimulation, peaked at 5-fold 6 h after hCG, and declined afterwards. Administration of cysteine (0.001-0.01 mmol) into the bursal cavity of proestrous rats blocked ovulation and breakdown of ovarian collagen in a dose-dependent manner. Cysteine effectively inhibited ovulation even when injected 7 h after the hCG stimulus. Inhibitors of arachidonic acid metabolism prevent ovulation. Indomethacin (inhibitor of cyclooxygenase) and nordihydroguaiaretic acid (inhibitor of lipoxygenase) blocked ovulation and inhibited hCG-induced ovarian collagenolysis. Collectively, these results corroborate the essential role of collagenolysis in follicular rupture in mammals.

Effect of cysteine on oltipraz blood levels in green monkeys (Cercopithecus aethiops).

Oral coadministration of oltipraz, an antischistosomal compound, with cysteine to green monkeys (Cercopithecus aethiops) led to a marked increase in both the extent and rate of oltipraz bioavailability. The drug blood levels were monitored using a single extraction gas-liquid chromatographic assay. When 6 healthy adult animals were given oltipraz together with cysteine in a crossover study, peak serum concentrations, areas under the curve and absorption rate constants of oltipraz were on average 7 times greater than when the drug was administered alone. Oltipraz peak serum concentrations were reached 1 h earlier as a result of cysteine administration (2 h after dosing). At present, the mechanisms responsible for the effect(s) of cysteine on oltipraz bioavailability have not been identified. The marked increase in oltipraz bioavailability produced by coadministration of cysteine, irrespective of the exact mechanisms involved, may have significant clinical implications with regard to the treatment of schistosomiasis. Our results also indicate that oltipraz blood levels seem to be influenced by some sex-related factors. Male monkeys had higher oltipraz blood levels than females. These sex-induced differences were more evident in oltipraz-cysteine-treated monkeys.

Synergistic induction of microsomal heme oxygenase activity in rat liver and kidney by diethyldithiocarbamate and nickel chloride

Microsomal heme oxygenase activity was measured in liver and kidney of rats killed after administration of sodium diethyldithiocarbamate (DDC) and nickel chloride (NiCl 2), singly and in combinations (DDC dosages: 0.33 to 1.33 mmol/kg, im, 17 hr before death; NiCl 2 dosages: 0.125 and 0.25 mmol/kg, sc, 17 hr before death). Syngergistic induction was observed at all dosage combinations. At the highest dosages of DDC and NiCl 2, the dual treatment induced heme oxygenase activity 11-fold in liver and 16-fold in kidney; at the same dosages given individually, DDC induction of heme oxygenase activity was 3-fold in liver and 2-fold in kidney, and NiCl 2-induction was 1.3-fold in liver and 6-fold in kidney. Synergistic induction of heme oxygenase activity in liver occurred when DDC was injected 6 hr before to 6 hr after NiCl 2; synergistic induction in kidney occurred when DDC was injected 6 hr before to 3 hr after NiCl 2. Actinomycin D prevented the induction of heme oxygenase activity by DDC or NiCl 2, given individually; the effect of actinomycin D on synergistic induction could not be measured, since the rats all died following treatment with DDC, NiCl 2, and actinomycin D. Administration of cysteine to rats, po, 18 hr before death, partially suppressed the induction of hepatic heme oxygenase activity by DDC, singly or in combination with NiCl 2. Synergistic induction of hepatic heme oxygenase activity also occurred in rats that received dual injections of DDC (1.33 mmol/kg, im) and hemoglobin (0.3 g/kg, iv); the synergism of DDC and hemoglobin, although statistically significant, was small in comparison to the striking synergistic effect of DDC and NiCl 2.

Biliary transport of glutathione and methylmercury

The hepatobiliary transport of glutathione (GSH) and methylmercury (MM) was investigated in male and female rats anesthetized with pentobarbital sodium. When bile flow was altered with either sodium dehydrocholate (DHC), hypertonic sucrose infusion, or by hypothermia, the absolute rates of GSH and MM secretion into bile were not affected, resulting in parallel concentration changes in the bile fluid for both GSH and MM. Indocyanine green and sulfobromophthalein (BSP), but not BSP-glutathione complex, inhibited the biliary secretion of free GSH. This inhibition was accompanied by a parallel inhibition of MM secretion into bile and occurred without any changes in liver GSH or MM levels. On the other hand, the intravenous administration of cysteine, GSH, and penicillamine was associated with an increase in the secretion rate of reduced sulfhydryl groups into bile and an increase in the biliary secretion rate of MM. The increased biliary secretion rate of MM after phenobarbital pretreatment was also associated with an increased rate of secretion of GSH into bile. In addition, sex differences and individual variability in the biliary secretion of MM were correlated with differing abilities to secrete GSH into bile. The results suggest the presence of a biliary transport system for GSH that determines the biliary secretion of MM.

The influence of some thiols on biliary excretion of methyl mercury.

N-Acetylpenicillamine and thiola increased biliary excretion of methyl mercury and sulfhydryl right after administration. Cysteine increased excretion of methyl mercury in bile after a temporary decrease following administration. During the interval of decreased mercury excretion biliary excretion of cysteine passed through a maximum. This indicates the existence of a common factor of the excretory systems for cysteine and methyl mercury and illustrates that cysteine cannot carry methyl mercury from liver to bile. Relatively large proportions of unchanged thiola and N-acetylpenicillamine were excreted in bile. Bile collected after administration of one of these compounds, in addition to thiola or N-acetylpenicillamine, contained other methyl mercury carrying components not present in control bile. From the experiments undertaken it cannot be stated whether these components play any role in the increased excretion of methyl mercury in bile caused by thiola and N-acetylpenicillamine. The mechanisms of increased biliary excretion of methyl mercury following administration of N-acetylpenicillamine, thiola and cysteine are discussed.

Protective role of endogenous pulmonary glutathione and other sulfhydryl compounds against lung damage by alkylating agents: Investigations with 4-ipomeanol in the rat

Because endogenous glutathione is known to participate in the detoxification of highly reactive, hepatotoxic drug metabolites, we studied the role of this substance in the pulmonary toxicity of 4-ipomeanol [1-(3-furyl)-4-hydroxypentanone] in rats. 4-Ipomeanol was an appropriate model for these studies since previous investigations have indicated that an alkylating metabolite, formed in situ, is responsible for selective lung damage by 4-ipomeanol. Toxic doses of 4-ipomeanol preferentially depleted rat lung glutathione. Pretreatment of animals with piperonyl butoxide, an inhibitor of the metabolic activation of 4-ipomeanol, prevented both the depletion of lung glutathione and the pulmonary toxicity of 4-ipomeanol. Prior depletion of lung glutathione by diethylmaleate increased both the pulmonary covalent binding and the toxicity of 4-ipomeanol, whereas administration of cysteine and cysteamine decreased both the covalent binding and the toxicity. These in vivo studies, in conjunction with previous in vitro studies which showed inhibitory effects of sulfhydryl compounds on the covalent binding of 4-ipomeanol, are consistent with the view that pulmonary glutathione plays a protective role against pulmonary alkylation and lung toxicity by 4-ipomeanol, probably by reacting with the toxic metabolite(s) to form nontoxic conjugate(s). Pulmonary glutathione may similarly provide protection against other electrophilic drugs or metabolites that can damage the lungs.

Effect of allylisopropylacetamide on glutathione metabolism in the rat liver. The possible role of glutathione in the induction of 5-aminolaevulinate synthase.

Administration of allylisopropylacetamide to rats caused a marked decline in the concentrations of reduced and oxidized glutathione in the liver. However, this decrease occurred in the presence of uninhibited activities of gamma-glutamylcysteine synthase and glutathione reductase, and unaltered activities of glutathione transferases A, B and C. The administration of cysteine, the rate-limiting precursor of glutathione formation, to rats treated with allylisopropylacetamide potentiated the inductive effects of the agent on 5-aminolaevulinate synthase, and markedly decreased the extent of decrease in glutathione concentrations by the agent. Conversely, the administration of diethyl maleate, which depletes the hepatic glutathione concentrations, to allylisopropylacetamide-pretreated rats (1h) diminished the extent of 5-aminolaevulinate synthase induction and the production of porphyrins by nearly 50%, when measured at 16h. This treatment did not alter the extent of non-enzymic degradation of liver haem by allylisopropylacetamide. When diethyl maleate was administered to the animals possessing high 5-aminolaevulinate synthase activity (at 3, 7 and 15h after allylisopropylacetamide), in 1h the enzyme activity was markedly decreased. Diethyl maleate had no effect on induction of 5-aminolaevulinate synthase by 3,5-diethoxycarbonyl-1,4-dihydrocollidine, also a potent porphyrinogenic agent. Diethyl maleate alone neither inhibited 5-aminolaevulinate synthase activity nor decreased the cellular content of porphyrins and haem. The data suggest that the decreases observed in the glutathione concentrations after allylisopropylacetamide administration are not the result of decreased production of the tripeptide. Rather, they most likely reflect the increased utilization of glutathione. The findings further suggest that the inhibition by diethyl maleate of allylisopropylacetamide-stimulated 5-aminolaevulinate synthase involves the inhibition of induction processes.

Methionine, pyridoxine and endothelial lesion in rats.

Methionine administered orally to rats produced a prolonged dose-dependent increase in endothelemia. The increase was observed after doses exceeding 100 mg/kg and was inhibited by a simultaneous administration of pyridoxine. The effect of methionine was also inhibited by trihydroxyethylrutoside and acetylsalicyclic acid. Endothelemia was increased furthermore by oral administration of cysteine and cystine and this increase was again inhibited by pyridoxine.

Therapeutic effectiveness of cystamine and cysteine to reduce liver cell necrosis induced by several hepatotoxins

Cystamine or cysteine administration to rats receiving dimethylnitrosamine, thioacetamide, or bromobenzene 3, 6, or 12 hr before, partially prevented the liver necrosis produced by these substances at 24 hr. In contrast, both chemicals were unable to prevent the necrosis induced by allyl alcohol and aflatoxin B 1. Since at either 6 hr (dimethylnitrosamine) or 12 hr (bromobenzene and thioacetamide), most of activation of the agents and the subsequent interaction with cell constituents has already occurred, these results suggest that cystamine or cysteine protect because they alter cellular response to the hepatotoxins. The results also suggest the possible application of these chemicals in therapeutics.

The interrelationship between non-protein bound thiols and the biliary excretion of methylmercury

The biliary excretion of methyl mercury was investigated in male rats injected with various thiol compounds, methionine and 3'-methyl-4-dimethyl-azobenzene (3'-MeDAB) after the i.v. administration of 1.0 mg kg of Hg as Me 20HgCl. All the thiol compounds (2 m-moles of glutathione (GSH) and 4 m-moles kg of cysteine, d-penicillamine or dimercaptosuccinic acid (DMSA) reduced the blood concentration of Me 203Hg +, but only cysteine, GSH and d-penicillamine increased the liver content of mercury and its biliary excretion. No significant changes were seen in the volume of bile flow after treatment. There was no correlation between the increase in non-protein thiol concentration in blood and either the liver content or the biliary excretion of Me 203Hg +. Although those thiol compounds that stimulated the biliary excretion of methylmercury also increased the liver concentration of non-protein thiol groups, there was no proportionality between either the extent or time course of these effects. An initial inhibition of excretion was caused by 4 m-moles kg of cysteine though the concentration of non-protein thiols in the liver was at that time the highest. After the administration of cysteine and GSH, excretion increased from 30 to 120 min while the concentration of non-protein thiols in the liver declined. 3'-Methyl-4-dimethylazobenzene (3'-MeDAB) and methionine caused a larger increase in liver non-protein thiol concentration than GSH but their effect on the biliary excretion of Me 203Hg + was smaller. On the assumption that d-penicillamine spares GSH from other metabolic processes, these results are consistent with the role of GSH in the biliary excretion of methylmercury. They do not support a direct relationship between free GSH and the biliary excretion of methylmercury.

Regulation of heme pathway enzymes and cellular glutathione content by metals that do not chelate with tetrapyrroles: blockade of metal effects by thiols.

The trace metals nickel and platinum, which are not substrates for ferrochelatase and thus do not form heme in biological systems, were found to act similaryl to cobalt, and heme itself, in regulating heme metabolism in liver and kidney. These metals induced heme oxygenase activity in both organs with the peak of induced enzyme activity reached approximately 16 hr after single injections in rats. Both metals caused transient depression of cellular glutathione content followed by increases above normal after 12 hr in liver. Nickel and platinum were more potent inducers of heme oxygenase in kidney than in liver (10-13 times normal versus 5-6 times normal). At high concentrations, they inhibited heme oxygenase [heme, hydrogen-donor:oxygen oxidoreductase (alpha-methene-oxidizing, hydroxylating), EC 1.14.99.3] in vitro. Both were active in regulating heme metabolism only when administered in the ionic form. Complexing of the metals with sulfhydryl agents completely blocked their actions on heme metabolism. Administration of cysteine orally prior to or shortly after administration of the metals had a similar blocking effect. Nickel and platinum produced depression of delta-aminolevulinate synthase [succinyl-CoA:glycine c-succinyltransferase (decarboxylating), EC 2.3.1.37] activity in liver, but neigther inhibited this rate-limiting ennzyme for heme synthesis in vitro. Furthermore, despite the substantial decreases in cellular heme and hemoprotein contents mediated by the metal, production of delta-amimolevulinate synthase did not undergo the compensatory increase that would be expected if there were a direct reciprocal feedback relationship between cellular heme level and synthesis of this enzyme. These findings indicate that it is not necessary for metal ions to be chelated in the porphyrin ring in order to regulate the enzymes of heme synthesis and heme oxidation. Accordingly, it is suggested that the iron atom of heme is the proximately active regulator of delta-aminolevulinate synthase and heme oxygenase--actions generally ascribed to the iron-tetrapyrrole complex itself--and that the tetrapyrrole moiety of the complex functions primarily as a means of transport of the metal to regulatory sites in cells.

The role of liver glutathione in the acute toxicity of retrorsine to rats

(1) Two procedures have been used to change the glutathione concentration in the livers of male rats. The glutathione level is increased to about double that of the controls, 0.5 h after the administration of cysteine (200 mg/kg, i.p.) and to about 25% that of controls, 1 h after the administration of 2-chloroethanol (30 mg/kg, i.p.). (2) The acute LD 50 of retrorsine to rats (42 mg/kg) is increased by pretreatment with cysteine to 83 mg/kg and decreased by pre-treatment with chloroethanol to 23 mg/kg. In all three groups, deaths are accompanied by haemorrhagic centrilobular necrosis of the liver. (3) 2 h after the administration of retrorsine to rats (60 mg/kg), the levels of pyrrolic metabolites in the livers of animals pre-dosed with cysteine or chloroethanol are respectively about 60% and 200% those of rats given no pre-treatment. (4) Neither in the normal nor m the pre-treated rats does retrorsine (60 mg/kg) cause a detectable fall in liver glutathione concentration 0.5–4 h after dosing. By 24 h, the glutathione concentration in the livers of the retrorsine-dosed rats is higher than those of the corresponding controls. There was no significant change in the liver weights of the treated rats relative to the controls. (5) Treatment of rats with retrorsine (60 mg/kg) causes a fall in the liver concentrations of cytochrome P-450, 24 h after dosing. This loss of cytochrome P-450 is increased in rats pre treated with chloroethanol. The concentrations of cytochrome b 5 in the same animals are not significantly reduced.

Die Rolle der Thioaminsäuren bei durch Kadmium hervorgerufenen experimentellen Hodenschädigungen

Simultaneous administration of cysteine and DL-ethionine in food protects, and enhances, respectively, the tissue damage produced by parenteral administration of cadmium (CdCl2) in testicles of rats. The effects are explained as an inactivation of SH-groups by cadmium, and in interference in cysteine metabolism by ethionine, respectively.

The possible protective effect of cysteine during acute alcohol intoxication

In the experimental conditions used, cysteine administered per os together with ethanol reduces the blood alcohol levels, but does not modify significantly the rate of alcohol oxidation. No effect of cysteine administration is however observed when ethanol is injected intraperitoneally. Cysteine addition in vitro enhances ethanol consumption by liver slices and reduces at the same time 14CO2 production from [2-14C] ethanol. This effect is only observed with a high cysteine/ethanol molar ratio. The changes in the blood alcohol level resulting from cysteine administration do not appear to result from such an interaction with ethanol oxidation, but seem to be due to a delayed ethanol absorption from the gastrointestinal tract.

EFFECT OF SULFHYDRYL-CONTAINING COMPOUNDS ON THE DIABETOGENIC ACTION OF STREPTOZOTOCIN

Most previous observations suggest the possibility that sulfhydryl-containing (SH) compunds may play a role in the regulation of carbohydrate metabolism. On the other hand, it is known that alloxan-induced diabetes may be partially prevented by the administration of glutathione and cysteine, which are without effect on streptozotocin (STZ) -induced diabetes. The present investigation was designed to re-examine whether SH-compounds would affect the diabetogenic action of STZ.Male Wistar rats weighing 200 to 250 gm were used in all experiments. SH-compunds were administered ip or iv 5-30 minutes before an intravenous injection of STZ (65 mg/ kg). There was a tendency to block the development of the STZ-diabetes when cysteine and 2-mercaptopropionyl-glycine were injected ip. The degree of the protective effect, with concomitant elevations of plasma SH content, was markedly enhanced when cysteine (10-1000 mg/kg) was administered iv. Blood SH content was lower in diabetic rats and patients with untreated diabetes mellitus than in controls.Thus the results of the present study clearly demonstrate that SH-compound could partially prevent the diabetogenic action of STZ. The effect of SH-group appears to be mediated through the common protective mechanism, at least in part, to the attacks of alloxan and STZ on the integrity of the pancreatic beta cell membrane.

The prevention by sulphydryl compounds of the toxicity in the cat of 2,6-dimethoxyphenol and its morpholinopropionyl ester.

1 Intravenous (minus)-2,6-dimethoxyphenyl-2-morpholinopropionate hydrochloride (M&B 16,573) produced anaesthesia of short duration in the mouse, rat, rabbit, cat, dog and monkey. In the cat but not in other species, a severe and usually fatal toxic reaction was seen 1-2 h after administration. 2 This toxic reaction but not the anaesthetic properties of M&B 16,573 was prevented by the intravenous administration of cysteine or N-acetylcysteine. Cysteamine or dimercaprol were ineffective. 3 Intravenous administration of 2,6-dimethoxyphenol or 2,6-dimethoxyquinol in the cat produced a response similar to the delayed toxic effects of M&B 16,573 but not preceded by anaesthesia. The toxic effects of these compounds were prevented by cysteine. 4 Intravenous 4-allyl-2,6-dimethoxyphenyl-2-morpholinopropionate hydrochloride produced anaesthesia in the cat without the delayed toxic effects seen after M&B 16,573. 5 The acute toxicity of 2,6-dimethoxyquinol in mice was reduced by the administration of cysteine or N-acetylcysteine. 6 It is postulated that the delayed effects produced by M&B 16,573 in the cat are due to the formation of 2,6-dimethoxyquinol and 2,6-dimethoxybenzoquinone in this species, the toxicity of the latter being reduced by sulphydryl compounds.

Mechanism of changes in the membrane potential in various types of muscle fibers in experimental tetanus

In early tetanus the fall in membrane potential (MP) of skeletal muscle fibers is nonspecific in character: it is connected with the development of hyperactivity of the muscles, and when this is abolished by division of the nerve, the MP of the skeletal muscle fibers returns to normal. In the late stage of tetanus poisoning the functional properties of the tetanic and tonic muscle fibers are altered to a greater degree than in early tetanus. Administration of ATP, cysteine, and phenylephrine appreciably raises the MP of the poisoned muscle fibers.

The curative effects of cysteamine, cysteine, and dithiocarb in experimental paracetamol poisoning.

In a curative test (i.p. injection 1 hr after administration of paracetamol) cysteamine (100 mg/kg), cysteine (200 mg/kg), and dithiocarb (100 mg/kg) reduced the death rate from paracetamol poisoning (1.5g/kg p.o.) in male mice from 67 to 10, 15 or 10%, respectively. A reduction of mortality rate to 30 or 35% was induced by glutathione (100 mg/kg) and thiazolidine carboxylic acid (50 mg per kg), respectively, whereas penicillamine, thioctic acid, silymarin, and dimercaprol were ineffective. When given 2 or 4 hrs after paracetamol, cysteine, unlike cysteamine, had a curative effect on paracetamol toxicity. Hepatotoxic activity of paracetamol (0.5 g/kg p.o.) was evident by high increases in the levels of serum enzymes (GOT, GPT, GLDH, SDH). Paracetamol-induced enzyme elevations were prevented completely by treatment with cysteamine (50 mg/kg) or cysteine (100 mg/kg) and partially by treatment with dithiocarb (100 mg/kg) 1 hr after paracetamol. LD50 values (i.p. injection) were 450 mg per kg for cysteamine, 660 mg/kg for cysteine, and 1800 mg/kg for dithiocarb. With regard to the therapeutic index cysteamine, cysteine, and dithiocarb can be recommended as antidotes for paracetamol poisoning. A nearly total depletion of hepatic glutathione occurred after paracetamol (0.5 g/kg p.o.). Administration of cysteine (100 mg/kg), one hr after paracetamol, induced a complete repletion of liver glutathione whereas cysteamine (100 or 200 mg/kg) and dithiocarb (100 mg/kg) induced a partial repletion. Glutathione repletion probably accounts for the antidote efficiency of cysteine, cysteamine, and dithiocarb. Its mechanism, however, remains obscure.

Prevention and treatment of carbon tetrachloride hepatotoxicity by cysteine: Studies about its mechanism

Cysteine administration to rats (1.9 g/kg po) prevented the development of the necrosis and fatty liver induced by CCl 4. This protective effect was observed when cysteine was given either 30 min before or 1 hr after the administration of CCl 4. Cysteine administration did not prevent the irreversible binding of 14C from 14CCl 4 to microsomal lipids, but it partially reduced the binding to microsomal proteins at 6 hr after 14CCl 4. Cysteine pretreatment did not modify the intensity of the CCl 4-induced lipid peroxidation process or cytochrome P-450 destruction, but it partially prevented depression of glucose-6-phosphatase activity by CCl 4. The results are compatible with the possibility of a protective action of cysteine at a site in the chain of events leading to necrosis, but not the activation step.