Effect of oral administration of T-2 toxin on glutathione shuttle enzymes, microsomal reductases and lipid peroxidation in rat liver

Effects of T-2 toxin on liver lipid peroxidation, glutathione shuttle enzymes and microsomal reductases have been studied in rats at 8, 16 and 24 hr after feeding a single dose of toxin (2.0 mg/kg) and at 7, 14 and 21 days after feeding of toxin (0.75 mg/kg) daily. Feeding of a single dose of T-2 toxin caused significant increase in liver lipid peroxidation in rats at 8, 16 and 24 hr post treatment. The liver lipid peroxidation was also significantly increased at 14 and 21 days after feeding of 0.75 mg/kg of T-2 toxin daily to rats. The activities of liver GSH-shuttle enzymes, i.e. glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, were significantly higher in rats after both feeding schedules of T-2 toxin. NADPH-cytochrome c reductase activity was significantly lower at 8, 16 and 24 hr in liver of rats fed a single dose of T-2 toxin, whereas NADH-cytochrome b5 reductase was significantly higher until 16 hr and then declined below normal at 24 hr post treatment. In rats fed multiple doses of T-2 toxin, both liver microsomal reductases were significantly reduced. These results suggest that T-2 toxin/or its metabolites in the liver may be involved in the generation of free radicals which cause the observed increase in lipid peroxidation.     

T-2 toxin induced changes in liver and serum enzymes of rats

The effects on liver and serum enzymes of feeding a single dose (2 mg/kg) and daily doses (0.75 mg/kg) of T-2 toxin were studied in young male rats. Sample times were 8, 16 and 24 hr for single dose administration and 7, 14 and 21 days for daily dose administration. T-2 toxin in single and daily doses significantly reduced activities of hepatic glutamate pyruvate transaminase (GPT) and alkaline and acid phosphatases at all the sampling periods. In both feeding trials, levels of serum GPT increased, while that of acid and alkaline phosphatases significantly decreased at all the sampling times. This study indicates that the liver is affected by feeding T-2 toxin to rats.     

Liver lipid metabolism in T-2 toxicosis

The acute effects of oral administration of a single dose of T-2 toxin (2.0 mg/kg body wt) to rats on whole liver lipid metabolism were studied at 8, 16 and 24 h post-treatment. Administration of T-2 toxin significantly increased liver and microsomal total lipids, free cholesterol, esterified cholesterol and triglycerides initially at 8 h, which subsequently returned to control values at 24 h. However, no significant alterations were observed in the contents of whole liver and liver microsomal total phospholipids and phosphatidyl choline, except that phosphatidyl ethanolamine and sphingomyelin + lysophosphatidyl ethanolamine contents in liver at 16 and 24 h and sphingomyelin + lysophosphatidyl ethanolamine content in liver microsomes at all three periods were significantly lower. The incorporation of 1-¹⁴C-acetate into whole liver and liver microsomal total lipids was reduced at 16 and 24 h post feeding. However, the incorporation of 1-¹⁴C-acetate into liver and microsomal free cholesterol, esterified cholesterol and triglycerides was significantly higher at 8 h, subsequently returning to the control value at 24 h; incorporation was significantly lower even into microsomal triglycerides. The incorporation of 1-¹⁴C-acetate into liver and its microsomal total phospholipids, phosphatidyl choline, phosphatidyl ehtanolamine and sphingomyelin + lysophosphatidyl ethanolamine, was significantly decreased at all three periods post toxin treatment. The results suggested that T-2 toxin inhibited the incorporation of ¹⁴C-acetate mainly into liver and its microsomal phospholipids and their subfractions in rats.     

Effect of T-2 toxin administration to rats on lipid metabolism in liver

The effect of oral dosing of rats with 1.5 mg T-2 toxin/kg body weight daily for 4 days on metabolism of liver lipids was studied. T-2 toxin significantly elevated total liver lipids, triglycerides, free cholesterol, total phospholipids and phosphatidyl choline, whereas the level of sphingomyelin + lysophosphatidyl ethanolamine was reduced. No change in the esterified cholesterol and phosphatidyl ethanolamine contents was observed. Incorporation of [1-14C]acetate into liver lipids, esterified cholesterol, triglycerides, free cholesterol and phosphatidyl ethanolamine was reduced in T-2 toxin-treated animals, implying reduced lipogenesis. Increased lipids in liver in T-2 toxin-treated rats are possibly due to an impaired secretion of lipids from the liver.     

Effects of Cortisol Administration on Components of the Hepatic Microsomal Mixed Function Oxidase System (MFO) of Immature Rainbow Trout (Salmo gairdnerii Rich.)

Abstract The effects of cortisol on components of the liver microsomal mixed function oxidase system (MFO) of immature and starved rainbow trout, Salmo gairdnerii, Rich., were studied 3, 7 and 21 days after intraperitoneal implantation of cortisol-containing cholesterol pellets. The treatment resulted in significantly elevated NADPH cytochrome c reductase activities, concomitant with elevated plasma cortisol levels, at all sampling events, while no significant effects on either liver cytochrome P-450 or microsomal protein contents was observed. The cortisol-treated fish lost considerably more body weight than corresponding controls during the experimental period, while the effects on liver wet weight and liver somatic index were inconclusive.     

Effect of chronic intoxication with (+)-amphetamine on its concentration in liver and brain and on (14C) leucine incorporation into microsomal and cytoplasmic proteins of rat liver

Rats were treated with increasing concentrations of (+)-amphetamine sulphate in drinking water for 90 days. The ingested dose of amphetamine was found to increase from 16 mg kg^?1 on the first day up to 90 mg kg^?1 on the 32nd day of treatment. The rats were maintained on the highest dose regime for a further 58 days without any deaths, which showed that tolerance to the overall toxicity of the drug developed. The concentrations of [³H]amphetamine in liver and brain of chronically treated rats were significantly higher than those of controls. Chronic treatment with amphetamine significantly reduced body and liver weight of rats, but did not influence the relative liver to body weight. A marked inhibition of [¹⁴C]leucine incorporation into liver microsomal and cytoplasmic proteins was observed after 90 days of treatment with amphetamine. The relation between inhibition of microsomal protein synthesis and the increase of amphetamine concentrations in liver and brain is discussed.     

Influence of dehydroepiandrosterone (DHEA) on cholesterol metabolism in rats

Wistar rats were fed semipurified diets containing 0.5% of dehydroepiandrosterone (DHEA) for 14 days. DHEA feeding resulted in weight loss and slight liver enlargement. It did not affect serum triglyceride levels but increased serum cholesterol levels. Liver triglyceride levels of DHEA-fed rats were significantly lower than in controls. DHEA inhibited cholesterol absorption. Liver slices from DHEA-fed rats incorporated more acetate into cholesterol than controls; there were no differences in conversion of mevalonate.     

Comparative in vitro metabolism of T-2 toxin by hepatic microsomes prepared from phenobarbital-induced or control rats, mice, rabbits and chickens

Hepatic microsomes were prepared from phenobarbital (PB)-treated and control rats, mice, rabbits and chickens and were incubated with T-2 toxin (100 micrograms/mg microsomal protein). Additional microsomes from PB-induced animals were incubated with T-2 toxin and the esterase inhibitor paraoxon (PA) at 2.5 nmol/mg microsomal protein. The major metabolite in microsomal preparations from both control and PB-induced rats, rabbits and mice was HT-2. In microsomes isolated from PB-treated chickens, 3'-hydroxy T-2 was the major metabolite, but 30 and 79% of the added T-2 toxin remained unmetabolized at 60 min in incubations from PB-induced and control birds, respectively. The percentage of hydroxylated metabolites formed in the microsomal preparations of the four species studied was significantly increased following PB treatment compared with the non-treated controls. The addition of PA to the incubation system effectively inhibited the hydrolysis of the ester groups in T-2 toxin, resulting in 1.4- and 1.25-fold increases in the percentage of 3'-hydroxy T-2 in the mouse and rat microsomal samples, respectively. In the rabbit microsomal preparations, 3'-hydroxy T-2, which was not detected in the absence of PA, represented 11% of the added substrate in the PB/PA incubation samples. Addition of PA did not cause a significant change in the amount of 3'-hydroxy T-2 formed in chicken microsomal samples, since competition between hydrolysis and hydroxylation pathways for the T-2 toxin substrate was not an important factor in this species. Two new metabolites, designated RLM-2 and RLM-3 were detected in chicken, rat and mouse microsomal preparations. On the basis of gas chromatography/mass spectrometry data, the compounds were tentatively identified as isomers of 3'-hydroxy T-2.     

Comparative effects of T-2 toxin and diacetoxyscirpenol on drug metabolizing enzymes in rat tissues

The effects of T-2 toxin and diacetoxyscirpenol on tissue drug-metabolizing enzymes in young male rats were compared. Mycotoxicoses were produced by daily oral administration of toxins at 1.0 mg/kg body weight for 1, 4 or 8 days. Many hepatic, renal and pulmonary oxidative and conjugative enzymes were measured in animals killed 24 hr following the last administration. The effects of the two trichothecene mycotoxins were generally similar. In liver the decrease in microsomal and cytosolic proteins paralleled the decline in total plasma proteins or the increase in plasma GOT activity. Hepatic microsomal cytochrome P-450 decreased in rats receiving trichothecenes for 8 days. This effect was more marked when aminopyrine, benzphetamine, ethylmorphine and ethoxycoumarin dealkylations or aniline and benzopyrene hydroxylations were measured. p-nitrophenol glucuronyltransferase activity was enhanced in animals receiving at least one administration of trichothecenes, whereas there was no change in conjugation to glutathione or acetate. In other tissues, there was no change in any renal enzymes whereas a significant rise in pulmonary monooxygenase was observed in T-2 toxin administered to rats for 4 or 8 days.     

Reversibility of hepatic changes caused by ethoxyquin

Ethoxyquin (6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline) was administered to rats at a dose level of 0.5 per cent in the diet for 14 days. It caused a marked increase in liver weight and induction of microsomal drug metabolizing enzymes. In contrast glucose-6-phosphatase activity was depressed. During a 30-day recovery period after removal of ethoxyquin the following parameters were monitored at intervals of 0, 3, 7, 14 and 30 days: liver weight, microsomal protein, cytochrome P-450, cytochrome b₅, biphenyl-4-hydroxylase, ethylmorphine-N-demethylase, glucose-6-phosphatase and DNA. Recovery appeared to be biphasic, specific enzyme activity and DNA concentration returning to normal in 3–7 days but, as a result of the slower return to normal liver size, total hepatic enzyme activity did not return to control levels until the 30th day.     

Enhancement of Cytosolic and Microsomal Glutathione S-Transferase Activities in Liver and Small Intestine from Female Rats During Lactation

Abstract: The influence of lactation on hepatic and intestinal glutathione S-transferase activities in mother rats was studied. Cytosolic and microsomal activities were assessed 7, 14 and 21 days after delivery, using 1-chloro-2, 4-dinitroben-zene as substrate. Cytosolic and microsomal activities from liver and small intestine determined 7 days post partum did not differ from those of virgin female rats. The hepatic cytosolic activity was significantly increased with respect to that of virgin females 14 days after delivery and tended to revert to the control value on day 21 of lactation, whereas the intestinal activity was increased on day 14 and remained augmented even 21 days post partum. Although the respective microsomal activities showed percent increases higher than those of the cytosolic enzymes, they both exhibited a similar pattern of stimulation in response to lactation.     

Effects of high sucrose diet on body and liver weight and hepatic enzyme content and activity in the rat

The effect of sucrose on the induction of hepatic and peripheral insulin resistance is well-documented. Studies show that, although oral administration of glucose does not significantly decrease total hepatic microsomal cytochrome P450 content, it causes an increase in cytosolic protein and in microsomal phospholipid and fatty acid content. In this study we examined the effects of a chronic high sucrose diet (HSD) on liver enzyme activity. Male Fisher 344 weanling rats were randomly assigned to a control diet (0% sucrose by calories, n = 10) or a diet in which starch was replaced by sucrose (65% sucrose, by calories, n = 10) for 90 days. The effects of HSD on weight gain, liver weight, hepatic microsomal cytochrome P450 (CYP450) content and glutathione-S-transferase (GST) activity were measured and compared with those fed standard lab chow. A small but statistically significant decrease in body weight (g) was seen in the sucrose-fed rats after day 50. Liver GST activity (nmol/mg protein/min) at the end of 90 days was decreased in animals maintained on HSD compared to those on the control diet, (181.7 +/- 8.0, 234.7 +/- 5.5), respectively. The liver weight and total CYP450 content in the two diet groups were not significantly different. The ratios of liver weight to body weight at the end of 90 days suggested that the livers of the HSD-fed animals were larger per gram of body weight. In addition, rats on the HSD had significantly smaller amounts of liver CYP450 1A1 and 3A2 than the rats on the control diet. These results suggest that a HSD may alter the hepatic enzyme activity which may affect the metabolism of substrates for these enzyme systems.     

T-2 toxin impairment of enteric reovirus clearance in the mouse associated with suppressed immunoglobulin and IFN-gamma responses

Trichothecenes are exquisitely toxic to the gastrointestinal (GI) tract and leukocytes and thus are likely to impair gut immunity. The purpose of this research was to test the hypothesis that the Type A trichothecene T-2 toxin interferes with the gut mucosal immune response to enteric reovirus infection. Mice were exposed i.p. first to 1.75 mg/kg bw T-2 and then 2 h later with 3 x 10(7) plaque-forming units of reovirus serotype 1, strain Lang (T1/L). As compared to vehicle-treated control, T-2-treated mice had dramatically elevated intestinal plaque-forming viral titers after 5 days and failed to completely clear the virus from intestine by 10 days. Levels of reovirus lambda2 core spike (L2 gene) RNA in feces in T-2-treated mice were significantly higher at 1, 3, 5, and 7 days than controls. T-2 potentiated L2 mRNA expression in a dose-dependent manner with as little as 50 microg/kg of the toxin having a potentiative effect. T-2 exposure transiently suppressed induction of reovirus-specific IgA in feces (6 and 8 days) as well as specific IgA and IgG2a in serum (5 days). This suppression corresponded to decreased secretion of reovirus-specific IgA and IgG2a in Peyer's patch (PP) and lamina propria fragment cultures prepared 5 days after infection. T-2 suppressed IFN-gamma responses in PP to reovirus at 3 and 7 days as compared to infected controls whereas IL-2 mRNA concentrations were unaffected. PP IL-6 mRNA levels were increased 2-fold 2 h after T-2 treatment, but no differences between infected T-2-exposed and infected vehicle-treated mice were detectable over the next 7 days. Overall, the results suggest that T-2 toxin increased both the extent of GI tract reovirus infection and fecal shedding which corresponded to both suppressed immunoglobulin and IFN-gamma responses.     

Maternal hepatic and embryonic effects of 1,2,3,4-tetrachlorobenzene in the rat

To assess possible maternal hepatic and reproductive effects of this uncharged, low molecular weight, lipophilic chlorinated benzene 0, 100, 300 and 1000 mg/kg/day of 1,2,3,4-tetrachlorobenzene (TCB) was orally administered to pregnant rats on days 9-13 of gestation and the animals were killed on day 14 of pregnancy. Phenobarbital and beta-naphthoflavone were administered to other pregnant rats as positive hepatic controls. Maternal mortality (7/19 rats) was increased and body weight gain was greatly decreased in the 1000 mg/kg/day TCB group. Liver to body weight ratio and hepatic microsomal protein content were unaffected by any TCB treatment. On day 14 maternal NADPH-cytochrome c reductase activity was increased at 1000 mg/kg/day, while the maternal hepatic microsomal cytochrome P-450 content was significantly induced by both 300 and 1000 mg/kg/day of TCB. Microsomal N-demethylation of aminopyrine was increased from 2.6 to 4.0 and 4.5 nmol/mg protein/min at doses of 300 and 1000 mg/kg TCB, respectively. However, maternal hepatic microsomal ethoxyresorufin O-deethylase activity was not consistently increased by TCB. Hepatic glutathione S-transferase activity towards 1,2-dichloro-4-nitrobenzene was increased only by the 1000 mg/kg/day TCB treatment. The rate of microsomal p-nitrophenol and phenolphthalein glucuronidation was increased by TCB administration. Embryonic growth was adversely affected by TCB treatment. Yolk sac diameter, embryonic crown-rump length, and head length were all decreased by treatment with 300 mg/kg/day TCB. This TCB treatment did not significantly elevate the number of dead or abnormal embryos.     

In vivo effects of T-2 mycotoxin on synthesis of proteins and DNA in rat tissues

Rats were given an ip injection of T-2 mycotoxin (T-2), the T-2 metabolite, T-2 tetraol (tetraol), or cycloheximide. Serum, liver, heart, kidney, spleen, muscle, and intestine were collected at 3, 6, and 9 hr postinjection after a 2-hr pulse at each time with [14C]leucine and [3H]thymidine. Protein and DNA synthesis levels in rats were determined by dual-label counting of the acid-precipitable fraction of tissue homogenates. Rats given a lethal dose of T-2, tetraol, or cycloheximide died between 14 and 20 hr. Maximum inhibition of protein synthesis at the earliest time period was observed in additional rats given the same lethal dose of the three treatments and continued for the duration of the study (9 hr). With sublethal doses of T-2 or tetraol, the same early decrease in protein synthesis was observed but, in most of the tissues, recovery was seen with time. In the T-2-treated rats. DNA synthesis in the six tissues studied was also suppressed, although to a lesser degree. With sublethal doses, complete recovery of DNA synthesis took place in four of the six tissues by 9 hr after toxin exposure. The appearance of newly translated serum proteins did not occur in the animals treated with T-2 mycotoxin or cycloheximide, as evidenced by total and PCA-soluble serum levels of labeled leucine. An increase in tissue-pool levels of free leucine and thymidine in response to T-2 mycotoxin was also noted. T-2 mycotoxin, its metabolite, T-2 tetraol, and cycloheximide cause a rapid inhibition of protein and DNA synthesis in all tissue types studied. These results are compared with the responses seen in in vitro studies.     

Effect of T-2 toxin on in vivo lipid peroxidation and vitamin E status in mice.

The effects of an acute administration of T-2 toxin on vitamin E status and the corresponding degree of lipid peroxidation, as determined by the plasma and organ content of malondialdehyde (MDA), was studied in mice. The effects of T-2 toxin administration on the body weight and weights of liver, spleen and thymus were also assessed. T-2 toxin was administered in doses ranging from 1 to 6.25 mg/kg body weight, depending on the experiment, while the dietary content of vitamin E ranged from near 0 to 5000 IU/kg. There was a significant decrease in vitamin E content of plasma after the administration of the toxin with the concentrations remaining low for periods as long as 48-72 h. MDA content of liver increased significantly after 24-48 h of toxin administration in contrast to the controls. However, MDA levels returned to the control range after 72 h. The concentrations of MDA in liver were inversely related to the vitamin E content of the diet, and were always higher for the toxin-treated animals (significant linear regression between MDA content of liver and the log10 of vitamin E content of the diet). Weights of spleen and thymus decreased after T-2 toxin administration; however, the weight of liver either increased or did not change in the different experiments. In conclusion, T-2 toxin treatment of mice increased lipid peroxidation in the liver as measured by MDA production. This process was maximal after 48 h of T-2 challenge, and decreased thereafter. Plasma alpha-tocopherol levels decreased as soon as 6 h after the toxin challenge, while MDA did not increase until there was a severe depletion of vitamin E. These changes were accompanied by decrease in weight of spleen and thymus.     

Effect of the mycotoxin citrinin on composition of mouse liver and kidney

A single i.p. dose of citrinin (35 mg/kg) caused significant increases in kidney weight of male mice at 24 and 48 hr, decreases in DNA and protein at 24 hr and RNA for 48 hr. In the liver, the DNA content of treated animals was significantly lower for the 48-hr period with decreases in liver RNA and protein only at 6 and 12 hr. Liver glycogen was significantly lower at 24 hr after treatment. Daily i.p. doses of citrinin for 4 days (15 mg/kg/day) induced a 12% decrease in the liver to body weight ratio. Daily i.p. administration of 30 mg citrinin per kg/day for 4 days caused death in 50% of the treated animals. Surviving animals showed decreased body weight, food consumption, per cent liver to body weight and liver glycogen. Liver protein was 78% higher than in controls. The kidney to body weight ratio was elevated 20% in treated animals but total kidney protein was depressed. Pathological changes produced by a single dose of citrinin (35 mg/kg, i.p.) were confined to the liver and included liposis in parenchymal and peripheral lobular zones, depletion of glycogen and increased parenchymal mitosis.     

In vivo and in vitro studies of the hepatotoxic effects of 4-chlorophenol in mice

4-Chlorophenol (4-CP) was studied for its toxicological effect on liver by using both in vivo and in vitro approaches. Male mice were administered 4-CP, 1.5 mmol/kg body weight, i.p., and were killed at 10, 20, 30 and 50 min after drug injection. Either i.p. or oral 4-CP administration significantly lowered total liver thiol levels by 20-30% after 30 min and 3 hr respectively. This time-dependent effect of 4-CP after i.p. treatment was enhanced when mice were pretreated with hepatic microsomal enzyme inducers (phenobarbital, 40 mg/kg body weight, b.i.d., 7 days; and beta-naphthoflavone, 80 mg/kg body weight once daily, 4 days). Further, the microsomal cytochrome P-450 inhibitor, SKF 525-A, 75 mg/kg body weight injected i.p. to mice 30 min prior to 4-CP administration, blocked the reduction of liver thiol content produced by 4-CP. The results suggest that a chemically reactive intermediate of 4-CP may be formed in liver which is responsible for the observed decrease in liver thiol content. Other investigations were done to characterize the in vitro irreversible binding of [14C]4-CP. [14C]4-CP was bound irreversibly to mouse liver microsomal proteins in a concentration-dependent manner. Binding was NADPH dependent and gave a maximal binding of 12.0 nmol/mg protein/20 min and an apparent binding constant of 0.222 mM. [14C]-Binding of 4-CP was increased by 155 and 127% in liver microsomes of phenobarbital- and beta-naphthoflavone. SKF 525-A, and CO:O2 (4:1, v/v)] and selected nucleophilic compounds (glutathione, L-cysteine or L-lysine) significantly reduced [14C]4-CP binding to mouse liver microsomes. An epoxide hydrolase inhibitor, cyclohexene oxide, did not alter the extent of irreversible binding, whereas scavengers of superoxide anions or agents that are reported to reduce accumulation of active semiquinone and quinone species (L-ascorbic acid, superoxide dismutase or epinephrine) decreased the binding of [14C]4-CP to mouse liver microsomal proteins by 56, 31 and 92% respectively. The data suggest that semiquinone and quinone species of 4-CP may be the chemically reactive intermediates leading to the in vivo reduction of liver thiol levels. Since 4-CP is a minor contaminant and possible metabolite of clofibrate and chemically related hypolipidemic agents, 4-CP and its metabolites may be partly responsible for some of the hepatotoxic effects seen after long-term administration of this therapeutic class of drugs.     

Lack of effect of streptogramins on hepatic drug metabolism enzymes in the rat.

Male Sprague-Dawley rats were treated with streptogramin derivatives (RP 7293, RP 54476, RP 57669, and RP 59500) or with the macrolide troleandomycin. Liver cytosol and microsomes were prepared, and the in vitro transformation of several model substrates studied. Furthermore, total and complexed microsomal cytochrome P-450 levels were compared. Hepatic cytochrome P-450 metabolite complexes were detected 4 days after troleandomycin treatment (500 mg/kg/day po), whereas such effects were not observed with po RP 7293 (500 mg/kg/day, 4 days) or with iv RP 54476 (12 mg/kg/day, 7 days), RP 57669 (6 mg/kg/day, 7 days), or RP 59500 (6 and 18 mg/kg/day, 7 days). The administration of troleandomycin resulted in statistically significant increases in liver weight (+20%), microsomal protein (+70%), total cytochrome P-450 (+187%), and cytosolic glutathione S-transferase activity (+32%). The activities of aniline hydroxylase, aminopyrine N-demethylase, and the high and low phases of 7-ethoxyresorufin O-deethylase were markedly decreased by 36% to 56%. In contrast, none of these hepatic parameters was changed significantly after administration of each streptogramin. These results suggest that streptogramins have not, in contrast to many commonly used macrolide antibiotics, had potent or specific effects on hepatic drug metabolizing enzymes in rats.     

Effect of chlorpromazine on protein, phospholipid and RNA synthesis or degradation in rat liver

Chlorpromazine (CPZ) administration to rats (25 mg/kg ip) significantly stimulated (14C)-leucine incorporation to liver microsomal proteins, (14C)-orotic acid incorporation to liver RNA and (32P) incorporation to liver microsomal lipids. CPZ administration did not modify the decay of radioactivity of liver microsomal lipids prelabeled with (32P) or that of microsomal proteins prelabeled with [(14C)-guanidino]-arginine. Results suggest that CPZ administration stimulates protein, phospholipids and RNA synthesis but does not affect their degradation. The relation of these findings with CPZ preventive effects on CCl4-induced liver injury is discussed.