Effects of ethanol on hepatic microsomal drug-metabolizing enzymes in the rat

The activities of several hepatic microsomal drug-metabolizing enzymes were determined in male and female rats after administration of 20% ethanol or an isocaloric amount of glucose in drinking water for 10–49 days. The aniline hydroxylase activity increased, whereas the activities of both pentobarbital hydroxylase and benzphetamine N-demethylase were decreased in male rats given ethanol and killed without ethanol withdrawal. Twenty-four hr after removal of ethanol, the aniline hydroxylase remained elevated but a striking increase of both pentobarbital hydroxylase and benzphetamine N-demethylase above control values occurred. Six days later, all three of these microsomal enzymes returned to normal control values. The reduction in pentobarbital hydroxylase and benzphetamine N-demethylase could not be attributed simply to high endogenous ethanol levels since: (1) addition of high concentrations of ethanol in vitro inhibited microsomal aniline hydroxylase and pentobarbital hydroxylase but did not reduce benzphetamine N-demethylase; and (2) acute administration of ethanol by gastric tube, which markedly elevated the blood ethanol level, did not result in a decline in the enzyme activities. These two findings suggest that the observed decrease in microsomal enzymes in male rats required persistent ethanol exposure. In contrast to male rats, female rats given ethanol for 28 days showed a significant increase in aniline hydroxylase activity, but the activities of pentobarbital hydroxylase and benzphetamine N-demethylase were not decreased. Moreover, administration of ethanol for 28 days to female rats did not reduce the response of these three enzyme activities to pentobarbital administration. It is concluded that the effects of chronic ethanol ingestion on the hepatic microsomal drug-metabolizing enzymes are complex and depend on sex, exposure to other agents and, most importantly, on the duration and proximity of ethanol intake.     

Selective inhibition of rat pulmonary monooxygenase by O, O, S-trimethyl phosphorothioate treatment

The effects of oral administration of O,O,S-trimethyl phosphorothioate (OOS), an impurity present in widely used organophosphorus insecticides, were studied using pulmonary and hepatic microsomal enzymes of rats. The animals were treated with OOS at 10, 20 and 40 mg/kg, and were killed on day 3 after treatment. Their relative lung weights increased markedly at 20 and 40 mg/kg, increasing 94% at the highest dose, whereas the weight of liver decreased. At 20 mg/kg OOS, the cytochrome P-450 content of the lung and liver decreased to 83 and 80% of the control levels respectively. Pulmonary microsomal 7-ethoxycoumarin (7-Ec) O-deethylase decreased in a dose-dependent manner; activities were less than 10% of control at the 40 mg/kg dose. The activity of pulmonary coumarin hydroxylase also decreased following OOS treatment, but the decrease was not dose-dependent since no activity was detectable at doses over 10 mg/kg. In contrast, the effect of OOS treatment on hepatic monooxygenase activity was moderate. 7-Ec deethylase activity was not affected by OOS treatment at any dose level, while p-nitroanisole (p-NA) demethylase activity was decreased only at the 40 mg/kg dose of OOS. Pulmonary malathion carboxylesterase activity was not affected by OOS treatment. In contrast, a dose-dependent decrease was observed in the liver carboxylesterase. Time course effects of OOS treatment on these parameters were examined by treating rats at 20 mg/kg. The animals were killed 0.5, 1, 3 and 7 days after the treatment. The 7-Ec deethylase activity of pulmonary microsomes was decreased on days 0.5, 1 and 3 after treatment, the maximum decrease being observed on day 1. Significant decreases were not observed in hepatic microsomal activities of 7-Ec deethylase or p-nitroanisole demethylase throughout the experimental period; rather, these activities were higher on day 7. Hepatic microsomal malathion carboxylesterase was lower on days 0.5, 1 and 3 after OOS treatment.     

Effects of chloroquine on lysosomal enzymes, NADPH-induced lipid peroxidation, and antioxidant enzymes of rat retina

Chloroquine (1, 5 and 10 mg/kg), given in acute and in chronic (7 and 15 days) treatment schedules, caused characteristic alterations in the lysosomal enzyme system, antioxidant enzymes, NADPH-induced lipid peroxidation, and glutathione content in the retina of the rat. One-half hour and four hours after chloroquine administration, increased free activities of lysosomal enzymes and NADPH-induced lipid peroxidation were observed, associated with a decrease in tissue glutathione content. In contrast to the acute effect, chloroquine, given in 7- and 15-day treatment schedules, had no significant effect on the lysosomal enzyme system, while at the same time a normalization or a decrease in NADPH-induced lipid peroxidation, associated with a significant increase in tissue glutathione content, was noted. Catalase and peroxidase activities were decreased after both the acute and the daily treatment schedules. Superoxide dismutase activity, although increased in the high dose acute study, appeared otherwise little affected by chloroquine treatment.     

Enhancement of microsomal monooxygenase,epoxide hydrase and udpglucuronyltransferase by aldrin,dieldrin and isosafrole administrations in rat liver

The effects of intraperitoneal administration of aldrin (10 mg/kg), dieldrin (10 mg/kg) and isosafrole (50 mg/kg) were investigated on the activities of drug biotransformation enzymes in rat liver. All the compounds studied were found to enhance the activities of microsomal monooxygenase (e.g. p-nitroanisoleO-demethylase, aryl hydrocarbon hydroxylase), epoxide hydrase (styrene oxide as substrate) and UDPglucuronyltransferase (p-nitrophenol as aglycone). Dieldrin, the epoxidized derivative of aldrin, was a more potent inducer than the parent compound itself. NADPH cytochrome c reductase activity was enhanced 2.5-fold, p-nitroanisole O-demethylase 7-fold, benzopyrene hydroxylase 2-fold, and epoxide hydrase 5-fold after treating rats with dieldrin for 6 days. The increase in activity of the microsomal UDPglucuronyltransferase could be only detected after an in vitro digitonin treatment of microsomal membranes, the enhancement being about 1.5-fold after administering dieldrin for 6 days.The administration of isosafrole to rats increased especially p-nitroanisoleO-demethylase activity in liver microsomes (10-fold in 3 days). NADPH cytochrome c reductase activity was increased 2-fold, cytochrome P-450 content 1.2-fold, benzpyrene hydroxylase activity 2.5-fold and epoxide hydrase activity 1.2-fold after treatment of rats for 3 days. UDPglucuronyltransferase activity increased 2.2-fold by treating rats for 6 dyas with isosafrole. This increase was, however, only to be seen in in vitro digitonin-activated microsomes due to the latency of UDPglucoronyltransferase.     

Effect of cigarette smoke inhalation on antioxidant enzymes and lipid peroxidation in the rat

Inhalation of cigarette smoke significantly increased glutathione (GSH) content and increased lipid peroxidation without altering the activities of Superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) or glutathione reductase (GR) in the lung (six male Wistar rats). Following intratracheal administration of benzo[a]pyrene (BP), an increase in pulmonary GSH-Px activity, GSH content and lipid peroxidation was observed after 12 h. GSH-Px activity and GSH content returned to control values by 7 and 30 days, respectively, whereas lipid peroxidation in the lung remained significantly greater than the control value for up to 7 days of BP administration. Hepatic activity of SOD was increased significantly, whereas the activities of GSH-Px, catalase, GR, and GSH content were not changed by inhalation of cigarette smoke. On administration of BP, a significant increase in the activities of SOD and GSH-Px was observed at 12 h. After 7 and 30 days, the activities of these antioxidant enzymes were comparable to their respective control group values. No change in the activity of catalase or in the level of lipid peroxidation was noted throughout the entire study period.     

Biochemical changes in subacute mycotoxicosis induced by T-2 toxin in rats

The intragastric administration to male Wistar rats of T-2 toxin at 1-1.3 mg/kg body weight for 7 days caused a sharp decrease in the liver activity of lysosomal enzymes: beta-galactosidase, beta-N-acetylglucosaminidase, alpha-mannosidase, cathepsins A, B, C and D and in the activity of enzymes of the 1st phase of metabolism of xenobiotics--aniline hydroxylase and carboxylesterase, as well as in the cytochrome P-450 level. At the same time, the subacute toxic effect of T-2 toxin was manifested in a significant increase in the activity of epoxide hydrolase and an enzyme of the 2nd phase of metabolism of xenobiotics--UDP-glucuronosyltransferase. A possible mechanism of the observed enzymological changes is discussed.     

Effect of Kalmegh extract on rat liver and serum enzymes

Oral administration of Kalmegh extract under acute (single dosage) and sub-acute (for 7 and 15 consecutive days) conditions at a dosage of 0.5 g dry leaf/kg/day to adult rats produced no change in the activities of glutamate oxaloacetic transaminase (GOT) and glutamate pyruvic transaminase (GPT) in liver and rerum. Administration of ethyl alcohol at a dosage of 0.2 g/kg/day (oral) for 7 and 15 consecutive days produced an appreciable increase in liver GOT and GPT activities. No appreciable change in serum GOT and GPT activities was observed under similar condition of treatment. Oral administration of a high dosage of ethyl alcohol (3 g/kg/day) produced significant increase in the activities of serum enzymes only. This alcohol-induced increase in serum transaminase activity became normal with pre- and post-treatment of Kalmegh extract (0.5 g/kg/day). This result suggests that Kalmegh extract protects alcohol-induced toxic-effect in liver tissue.     

Chronic phenytoin administration and the hepatic mixed function oxidase system in female rats

The long term effects of phenytoin administration on mixed function oxidase activities and serum estradiol in female rats were examined. No induction of hepatic mixed function oxidases was seen until 8 days after the administration of 100 mg phenytoin/kg/day either orally or intraperitoneally. Maximum increase in aniline hydroxylase, aryl hydrocarbon hydroxylase (AHH) and ethylmorphine-N-deethylase activities occurred between days 8 and 16 of treatment and decreased thereafter. No induction of lung or intestinal AHH activity was observed. Serum levels of estradiol were significantly decreased after 16 days of phenytoin treatment. Maximal increases in hepatic cytochrome P-450 and cytochrome c reductase occurred after 8-16 days of treatment. Furthermore, pentobarbital sleeping times were shortest after 16 days of phenytoin administration. The activities of all enzymes after 32 days of phenytoin treatment were less than at the peak activities at 8-16 days.     

Reversible, hepatic, lysosomal phospholipidosis in rat induced by subchronic daily administration of trospectomycin sulfate

Trospectomycin sulfate is an experimental aminocyclitol antibiotic which has been shown previously to induce the formation of cytoplasmic lamellar bodies in rat and dog liver in subchronic experiments. The effect of repeated daily administration of trospectomycin sulfate on hepatic phospholipid levels and activities of marker enzymes for subcellular organelles was examined. Rats were treated for 30 or 90 days with 0, 50, or 250 mg/kg/day of trospectomycin sulfate prior to being killed, and another group was dosed for 90 days and then allowed to recover for 79 days prior to sacrifice. Transmission electron microscopy showed the presence of lamellar bodies in hepatocytes in both 50 and 250 mg/kg groups at 90 days but no other apparent changes in cellular morphology. Total phospholipids were increased significantly (1.6-fold) only at 90 days (P less than 0.01) and only in the 250 mg/kg group. Phosphatidylcholine, phosphatidylinositol, and two acidic lysosomal phospholipids, bis(monoacylglycero)phosphate and acylphosphatidylglycerol, accounted for 42, 35, and 21% of the increase in total phospholipids. Changes in the activities of marker enzymes were generally confined to the 250 mg/kg group at 90 days, with the largest and most significant increases being in the lysosomal enzymes acid phosphatase and hexosaminidase (P less than 0.01). Levels of all phospholipids and marker enzymes, with the exception of succinate dehydrogenase, were not significantly different from controls 79 days after cessation of dosing, and lamellar bodies had disappeared. We conclude that repeated trospectomycin sulfate treatment in rat induces a reversible, dose- and time-dependent lysosomal phospholipidosis in liver which is characterized by an increase in lysosomal enzymes and selected anionic phospholipids.     

Effect of excess and deficient copper intake on rat liver microsomal enzyme activity

The effect of copper loading and copper deficiency on rat liver microsomal enzyme activity was studied. A significant reduction of liver aniline hydroxylase activity was produced by the administration of 450 ppm copper in the drinking water to rats for 15 and 30 days. Lower levels of copper (50 and 150 ppm) administered to rats for the same time had no significant effect on enzyme activity. Copper loading did not alter the activities of liver glucose 6-phosphatase or benzpyrene hydroxylase. Aniline hydroxylase and hexobarbital oxidase activities were significantly reduced, and hexobarbital sleeping time was prolonged in copper-deficient rats. Liver enzyme activities and hexobarbital sleeping times were restored to control levels by feeding copper- deficient rats a copper-containing diet for 14 days. The addition of divalent copper in vitro to 10,000 g supernatants from liver homogenates from copper-deficient rats did not restore enzyme activity to control levels. Instead, high levels of added copper produced a decreased rate of aniline hydroxylation in vitro. Copper deficiency did not prevent the induction of liver microsomal enzyme activity by phenobarbital. Phenobarbital administration significantly increased microsomal copper in rats receiving a normal copper intake and increased both whole liver and microsomal copper concentration in copper-deficient rats. The normal developmental increase in liver aniline hydroxylase and hexobarbital oxidase activities with age was delayed in the offspring of female rats maintained on a copper-deficient diet.     

Effects of methylmercuric chloride intoxication on the intracellular activity of lysosomal enzymes in rat liver and brain

The activity of the lysosomal enzymes of rat liver after a single intraperitoneal injection of methylmercuric chloride (5.0 mg/kg) was enhanced in the nuclear fraction during early post-injection (2 hr to 7 days), while it decreased in the mitochondrial fraction and increased in the lysosomal fraction during late post-injection (14 days). Rat brain activity, however, was reduced in the nuclear, mitochondrial and lysosomal fractions during late post-injection (14 days). A high accumulation of total mercury was observed in the liver during early post-injection (36 hr and 7 days) while similar accumulation in the brain occured during late post-injection (7 days and 14 days). Both the mercury burdens and the enzyme activities of the rat liver and brain returned to normal levels within 30 days.     

Effect of acrylamide on brain and hepatic mixed-function oxidases and glutathione-S-transferase in rats

Effect of acrylamide on rat hepatic and brain mixed-function oxidases and glutathione-S-transferase was investigated. Administration of acrylamide (25 mg/kg) for 7, 14, 21, and 28 days showed no significant effect on hepatic and brain mixed-function oxidases at 7 days whereas a slight increase in the activity of hepatic glutathione-S-transferase was observed. Brain glutathione-S-transferase remained unaffected at this treatment schedule. At 14 days of acrylamide exposure, all the hepatic mixed-function oxidases with the exception of aminopyrine-N-demethylase and brain aryl hydrocarbon hydroxylase showed a decrease, and by 21 days all the hepatic and brain mixed-function oxidases were significantly decreased. The decrease in enzyme activities was also evident at 28 days of acrylamide treatment. Hepatic glutathione-S-transferase returned to normal level at 14 days of acrylamide exposure. Both hepatic and brain GST showed a significant decrease at 21 and 28 days of acrylamide treatment. Administration of acrylamide at 50 mg/kg for 3, 6, and 10 days produced no changes in hepatic and brain glutathione-S-transferase activity at early time periods (3 and 6 days). A significant decrease in glutathione-S-transferase activity of both tissues was seen at 10 days of acrylamide exposure. Hepatic mixed-function oxidases showed no change at 3 days but significant decrease at 6 and 10 days of acrylamide exposure. Brain mixed-function monooxygenase activity at this dose was inhibited even after 3 days of acrylamide treatment. The results suggest that acrylamide interferes with xenobiotic metabolism in both liver and brain.     

Effect of aloe vera leaf gel extract on membrane bound phosphatases and lysosomal hydrolases in rats with streptozotocin diabetes

Diabetes mellitus is known to promote deterioration of membrane function and impair intra cellular metabolism in the organism. The aim of the present study was to examine the effect of the ethanolic extract from Aloe vera leaf gel on membrane bound phosphatases and lysosomal hydrolases in the liver and kidney of streptozotocin (STZ)-induced diabetic rats. The rats treated with STZ showed significant alterations in the activities of membrane bound phosphatases and lysosomal hydrolases in the liver and kidney. Oral administration of Aloe vera gel extract at a dose of 300 mg/kg body weight/day to STZ-induced diabetic rats for a period of 21 days significantly restored the alterations in enzymes activity to near normalcy. These results were compared with glibenclamide, a reference drug. Thus, the present study confirms that Aloe vera gel extract possesses a significant beneficial effect on membrane bound phosphatases and lysosomal hydrolases.     

Aryl hydrocarbon hydroxylase activity induced by injected diesel particulate extract vs inhalation of diluted diesel exhaust

The effects of long-term inhalation of diluted diesel exhaust on aryl hydrocarbon hydroxylase activity (AHH) and cytochrome P-450 content in lung and liver microsomes were investigated in male Fischer-344 rats and compared with repeated parenteral administration of organic solvent extracts of hydrocarbons adsorbed on the diesel particulate surface during the combustion process. The animals were exposed to concentrations of 750 micrograms m-3 or 1500 micrograms m-3 of diesel particulates from a 5.7L GM diesel engine 20 h per day, 5 1/2 days per week for up to 9 months or treated by repeated IP injections of diesel particulate extract (dissolved in corn oil) from the same engine at several dose levels for 4 days. No significant effects of long-term inhalation exposure were observed in liver microsomal AHH activity. A slight decrease in lung microsomal AHH activity was found in rats following 6 months of exposure to diesel exhaust at the particulate concentration of 1500 micrograms m-3. The total mass of particles deposited in the lung during the inhalation exposure was estimated and an equivalent dose of extractable hydrocarbons was administered intraperitoneally; no increase in AHH activity was observed in the lung or liver microsomes. In contrast, 1.4- to 9-fold increases in AHH activity were observed in liver and lung microsomes of rats pretreated by intraperitoneal doses 10-50 times larger than the most conservative estimate of the deposited lung burden. No changes in cytochrome P-450 content were observed in the microsomes of rat liver after inhalation or injection treatment studies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatotoxicity in albino rats exposed to n-octane and n-nonane

Effects of n-octane and n-nonane (1 ml per kg body weight daily) on hepatic and serum enzymes, which reflect abnormal liver function and concentration of lipid and nucleic acid (serum and liver), were studied after 2 and 7 days intraperitoneal administration to albino rats. Decreased activities of serum acetylcholine esterase and carboxyl esterase were observed, together with an increase in FDP aldolase activity. Significant decrease in the concentration of albumin, total protein, and total and esterified cholesterol in serum have been noted after n-octane and n-nonane administration for 7 days. Also, free cholesterol content of liver was elevated significantly after solvents exposure.     

Effects of vitamin A deficiency on hepatic and extrahepatic mixed-function oxidase and epoxide-metabolizing enzymes in guinea pig and rabbit.

Male guinea pigs and male rabbits were fed a vitamin A deficient diet for 9 weeks and for 12 weeks respectively. Hepatic levels of vitamin A were significantly reduced in the vitamin A deficient animals. The activities of some xenobiotic-metabolizing enzymes were measured in the liver, lung and small intestine. Aryl hydrocarbon hydroxylase, aniline hydroxylase, and 7-ethoxycoumarin deethylase activities were decreased in the vitamin A deficient guinea pig liver. However, in the guinea pig small intestine, aniline hydroxylase, 7-ethoxycoumarin deethylase, aminopyrine demethylase, and aryl hydrocarbon hydroxylase specific activities were increased. In rabbits, vitamin A deficiency decreased hepatic aniline hydroxylase and 7-ethoxycoumarin deethylase activities but increased intestinal aminopyrine demethylase activity. Enzyme activities in lung were not altered by vitamin A deficiency in guinea pig or rabbit. Microsomal epoxide hydrase and microsomal supernatant glutathione S-transferase activities in the three tissues of both species were not altered by vitamin A deficiency.     

Role of lycopene in recovery of radiation induced injury to mammalian cellular organelles

Whole body exposure of male rats to 7 Gy gamma irradiation increased lipid peroxidation in the liver resulting in biomembrane damage of subcellular structures and release of their enzymes. This is evidenced by increase of thiobarbituric acid-reactive substances (TBARS) in mitochondria, lysosomes and microsomes. This was associated with a decrease in activity of the enzymes specific for each subcellular fraction; namely, mitochondrial glutamate dehydrogenase (GDH), lysosomal beta-glucuronidase and microsomal glucose 6-phosphatase. This was paralleled by an increased activity of these enzymes in the cytosol. Rats were supplemented with lycopene, a carotenoid present in tomatoes (5 mg/kg weight/day), by gavage, for 7 days before exposure to 7 Gy gamma irradiation. This resulted in diminishing amount of TBARS recorded for each subcellular structure in the liver of irradiated animals. Significant amelioration in the decrease recorded for the activity of mitochondrial glutamate dehydrogenase, lysosomal beta-glucuronidase and microsomal glucose 6-phosphatase was observed. This was associated with significant amelioration in the increase recorded for the activity of these enzymes in the cytosol. It is postulated that lycopene could play an important role in the recovery of the integrity of biological membranes of the liver after radiation injury.     

Effects of the anticancer dehydrotarplatin on cytochrome P450 and antioxidant enzymes in male rat tissues

The effect of dehydrotarplatin (DTP), a new antineoplastic drug analogous to cisplatin, and its metabolite (Triacid) on the hepatic, renal and testicular CYP and antioxidant enzymes of male rats was investigated. The rats were treated i.p. with a single dose of DTP (25 mg kg⁻¹ day⁻¹) or Triacid (17.5 mg kg⁻¹ day⁻¹) and analysed 3 or 7 days post treatment. Three days after treatment, both drugs reduced body and liver weights, which partially recovered the control level after 7 days. DTP and, to a less extent, Triacid caused a depletion of plasmatic testosterone content and a down regulation in the liver of androgen dependent male specific CYP 2C11, but not of CYP 1A and 2E1, as determined by a significant decrease of 2α- and 16α-testosterone hydroxylase activities (markers for CYP 2C11) and of apoprotein immunoreactive with anti-rat CYP 2C11 antibodies. However, the activity of testicular 17α-progesterone hydroxylase, a key reaction in steroidogenesis, was not altered by these drugs. The DTP and Triacid administration did not cause any alteration of the plasmatic urea nitrogen and creatinine, known as markers of kidney toxicity. However, treatment with DTP, not Triacid, either 3 and 7 days post treatment, caused in the kidney microsomes a significant increase of the total CYP content, the CYP 4A-dependent (ω)- and (ω − 1)-lauric acid hydroxylase activities and apoprotein immunoreactive with anti-rat CYP 4A1. The present study also examined the enzymatic antioxidant status of kidney and liver. Neither DTP nor Triacid administration induced, with respect to control values, any alteration of hepatic and renal glutathione reductase, glutathione S-transferase, catalase, superoxide dismutase activities, hepatic GSH level and renal microsomal lipid peroxidation level. Among the antioxidant enzymes assayed, only the renal activity of glutathione peroxidase was significantly increased after DTP but not Triacid treatment. These results indicate that DTP at a dose of 25 mg/kg and Triacid cause a feminization of the CYP enzymes in male rat liver similar to that reported for cisplatin when administered at a low dose (5 mg/kg). However, unlike cisplatin, DTP and its metabolite were unable to enhance BUN and creatinine and cause any depression of CYP activities and antioxidant enzymes in the kidney, suggesting that DTP may have low or even no potential in inducing nephrotoxicity.     

Effects of gomisin A, a lignan component of Schizandra fruits, on experimental liver injuries and liver microsomal drug-metabolizing enzymes

Effects of oral administration of gomisin A, one of the components isolated from Schizandra fruits, on liver injuries induced by CCl4, d-galactosamine and dl-ethionine and on liver microsomal drug-metabolizing enzyme activities were investigated. Gomisin A suppressed the increase of serum transaminase activities and the appearances of histological changes such as degeneration and necrosis of hepatocyte, inflammatory cell infiltration and fatty deposition in each type of liver injury. The repeated administration of gomisin A (30 or 100 mg/kg, p.o., daily for 4 days) induced an apparent increase of liver weight in liver-injured and normal rats. Gomisin A decreased serum triglyceride and lipid contents of the liver in biochemical studies. Increases of microsomal cytochrome b5 and P-450, elevations of NADPH cytochrome C reductase, aminopyrine N-demethylase and 7-ethoxycoumarin O-deethylase activities and decrease of 3,4-benzo(a)pyrene hydroxylase activity per cytochrome P-450 were observed after the administration of gomisin A. In addition, gomisin A was found to enhance the incorporation of 14C-phenylalanine into liver protein and to shorten the hexobarbital-induced sleeping time. These changes caused by gomisin A were similar to those by phenobarbital. However, gomisin A is distinctly different from phenobarbital in the finding that phenobarbital lessened the survival ratio of CCl4-intoxicated mice, but gomisin A did not. Our observation suggest that gomisin A shows an antihepatotoxic action by oral application and also has hypolipidemic (mainly triglyceridemic) and liver protein synthesis-facilitating actions and that the enlargement of the liver seen with gomisin A is the adaptive hypertrophy which is due to the induction of drug-metabolizing enzymes.