This study was carried out to evaluate the antitumor, hepatoprotective and antimutagenic activities on hot water extract of Phellinus gilvus (PGE). Growth of tumor in mice that were orally given 0.25, 0.5, 1.0, 2.0 gㆍkg-¹ dose of PGE was inhibited in a dose-dependant manner (p less than 0.05). The hepatoprotective effect of PGE in the carbon tetrachloride (CCl₄)-intoxicated rats was studied. In CCl₄+PGE groups, PGE was orally administered with 100 mg/kg/day dose 7 days before the treatment of CCl₄. The serum activity of aspartate aminotransferase and alanine aminotransferase in CCl₄+PGE group were decreased at a rate of 59.6% and 54.1% compared with those in CCl₄ group, respectively (p less than 0.05). Also, total cholesterol and triglyceride in CCl₄+PGE group were significantly decreased at a rate of 90% and 73.6% compared with those in CCl₄ group (p less than 0.05). In the Ames test, we confirmed PGE doesn't have any activity as a mutant, and PGE showed inhibitory effect against mutagenesis induced by 2-amino fluride and sodium azide in Salmonella typhimurium TA98, TA100 and TA 1535 in a dose-dependent manner. From the above results, we may suggest that PGE might have useful as a material for functional food and/or animal pharmaceutics.

This study investigated the protective effects of ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), an extracellular calcium chelator, and ethylenediaminetetraacetic acid (EDTA), which chelates calcium and most metal ions, against carbon tetrachloride (CCl₄)-induced acute hepatotoxicity in mice. Mice were treated with EGTA or EDTA at a dose of 20 (low) or 100 mg/kg (high) subcutaneously 1 h before CCl₄ administration. The mice were fasted and sacrificed 18 h after CCl₄ treatment.

The kiwi (Actinidia deliciosa) is well known to contain anti-oxidants. In this study, we investigated the anti-oxidant effects of kiwi extract on carbon tetrachloride (CCl₄) induced liver injury in BALB/c mice. The radical scavenging effect of 80% methanol extract of Halla-Gold kiwi was observed. For the animal study, mice were randomly divided into four groups: normal group, CCl₄-induced model group, kiwi extract administered group, and silymarin treated group. The kiwi extract was provided daily for 10 days. At the 24 h after last administration, CCl₄ was injected. The kiwi extract showed strong inhibitory effect of DPPH radicals and superoxide scavenging. In animal study, administration of CCl₄ resulted in significantly elevated plasma levels of ALT and AST but they decreased in kiwiextract pretreated group. Anti-oxidant enzymes such as GSH-px and GSH-rd were restored in the kiwi extract treatment group. Histopathological degeneration was also prevented in the kiwi extract treated group compared with of the control group, which exhibited CCl₄-induced hepatotoxicity. On the basis of the obtained results, it can be concluded that kiwi extract showed protective effects, not only as anti-oxidant effects, but also in the protection of hepatotoxicity in CCl₄-intoxicated mice.

Several compounds and extracts isolated from a brown alga, Ishige (I.) okamurae, exhibit anti-oxidant and anti-inflammatory effects. The present study investigated whether the ethyl acetate (EtOAc) fraction of I. okamurae (EFIO) could ameliorate carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. Sprague-Dawley rats were intraperitoneally (i.p.) administered with EFIO at 10 or 50 mg/kg per day for 2 consecutive days before CCl₄ injection (3.3 mL/kg, i.p.). Twenty four hours later, the rats were anesthesized with diethyl ether and dissected. Pretreatment with EFIO significantly reduced the increased serum levels of alanine aminotransferase and aspartate aminotransferase in CCl₄-treated rats. Pretreatment with EFIO also significantly inhibited the reduced activities of superoxide dismutase and catalase in the CCl₄-injured liver. Histopathological evaluations showed that hemorrhage, hepatocyte necrosis, inflammatory cell infiltration, and fatty degeneration induced by CCl₄ treatment were ameliorated by the administration of EFIO. Additionally, liver immunohistochemical analyses revealed the marked reduction in ED1-positive monocyte-like macrophages in EFIO-pretreated rats given CCl₄. These results suggest that EFIO ameliorates CCl₄-induced liver injury, possibly through the inhibition of oxidative stress.

This study was carried out to find whether phenidone (1-phenyl-3-pyrazolidinone), a cyclooxygenase as well as a lipoxygenase inhibitor, exhibits the preventive effect on carbon tetrachloride (CCl₄)-induced acute liver injury in rats. Rats were pretreated with phenidone at a dose of 50 or 200 mg/kg (p.o.) once daily for 3 consecutive days before CCl₄ administration. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Malondialdehyde (MDA) production was determined as an index of lipid peroxidation in the liver and serum. The histopathological changes in the liver were also examined in each group. The reduction in body weights was significantly inhibited in the phenidone-treated group than in the CCl₄ control group. Significant increase in the relative liver weights of the phenidone-treated groups was observed compared with either the vehicle or CCl₄ groups. Elevation of serum AST and ALT activities occurred after CCl₄ treatment was significantly attenuated by the pretreatment with phenidone. The elevation of MDA levels in liver and serum were completely inhibited in phenidone-treated groups. The protective effects on phenidone-treated groups were confirmed histopathologically. These results suggest that phenidone may be a useful protector through modulation of hepatic inflammation in CCl₄-induced acute liver injury.

Alterations in serum lipid and lipoprotein concentrations in ponies with experimentally induced liver disease were investigated. Hepatocellular damage was induced, using a nonlethal dose of carbon tetrachloride. In a separate group of ponies, obstructive jaundice was induced by surgical ligation of the common bile duct. Over a 6-day period, blood samples were obtained from ponies after treatment with carbon tetrachloride and for 12 days in ponies subjected to surgery. Serum cholesterol and triglyceride concentrations were unaffected in both groups of ponies, except for significantly (P < 0.01) high triglyceride concentration in ponies of the ligated group during the second postsurgical week. This increase was most likely attributable to anorexia observed during that period. Hyperbilirubinemia was observed early in ponies of the ligated group; most of the bilirubin was of the conjugated type. Using electrophoretic and ultracentrifugal methods, serum lipoprotein alterations were detected only in ponies of the ligated group. Increases of very low-density and low-density hpoprotein cholesterol concentrations and decrease in high-density lipoprotein cholesterol concentration were found. Although no changes were seen in total serum cholesterol concentration, a redistribution of lipoprotein cholesterol was observed in ponies of the ligated group. Similar alterations in lipoprotein distribution have been found in dogs, rats, and human beings with obstructive jaundice and cholestasis. The association between serum lecithin:cholesterol acyl transferase activities and these lipoprotein alterations remains to be elucidated.

Pleurotus cornucopiae (PC) mushrooms are found in the field and commonly known in Japan as Tamogidake mushrooms. The present study investigated the protective effects of an aqueous extract of PC on carbon tetrachloride (CCl4)-induced hepatotoxicity and the possible mechanism involved in this protection including cytochrome P450 (CYP) 2E1. Wistar rats were pretreated with aqueous extracts of PC (0, 100, 200, and 400 mg/kg) orally for 8 days prior to the intraperitoneal administration of a single dose of CCl4 (0.5 ml/kg) or corn oil. Pretreatment with PC mushroom extract significantly prevented the increased serum enzyme activities of alanine and aspartate aminotransferases in a dose-dependent manner, and suppressed the expression of CYP2E1. PC mushroom extract also protected hepatocytes from the damage effects of CCl4 as remarked by histological and electromicroscopical findings. It was concluded that repeated daily doses of aqueous extracts of PC mushroom reduced the toxic effects exerted by CCl4 on the liver.

We have investigated the accumulation of diacylglycerol (DAG) induced by carbon tetrachloride (CCl4)-derived radicals in the liver of female Sprague-Dawley (SD) rats after intraperitoneally injecting CCl4. DAG is an intracellular activator of protein kinase C (PKC) which regulates cell proliferation and differentiation. The electron spin resonance (ESR) study gave the signal of the PBN-CCl3 adduct in the liver of the rats which were pretreated with PBN, confirming that CCl4 was metabolized into CCl3-radicals with cytochrome P450 enzyme and indicating that PBN could trap them. The blood biochemical assay supported the trapping of the CCl3-radicals; the pretreatment of rats with PBN inhibited the increase in the GOT and GPT values upon exposure to CCl4. The Fourier transform-infrared (FT-IR) study indicated in comparison with the model compounds that the CCl4-injected rats accumulated DAG in addition to phosphatidylcholine, phosphatidylethanolamine and triglyceride (TG) in the lipid membrane fraction of the liver homogenate. DAG was found to be ca. 10-15% of the membrane phospholipids by weight. However, DAG was not found in the lipid of the liver microsomes, suggesting that it is formed only in the cell membrane of liver. Also, neither DAG nor TG was found in the lipid membrane of the rats that were pretreated with PBN followed by an injection of CCl4. The formation of DAG was confirmed by an HPLC study. The activation of PKC was observed in liver homogenate in the rats that were injected with CCl4. On the basis of the above findings, it was concluded that the CCl4-derived radicals stimulate PKC through the accumulation of DAG in the liver membrane of the rats. Furthermore, it was shown that PBN has a protective and therapeutic effect against CCl4-induced damage

Nigella sativa (family Ranunculaceae ) is an annual plant that has been traditionally used on the Indian subcontinent and in Middle Eastern countries. In this study, we investigated the effect of N. sativa oil on the drug-metabolizing cytochrome P450 (CYP) enzymes and whether it has a protective effect against the acute hepatotoxicity of CCl4. Intraperitoneal injection of rats with CCl4 drastically decreased CYP2E1, CYP2B, CYP3A2, CYP2C11, and CYP1A2 mRNA and protein expressions. Oral administration of 1 ml/kg N. sativa oil every day for one week prior to CCl4 injection alleviated CCl4-induced suppression of CYP2B, CYP3A2, CYP2C11, and CYP1A2. Moreover, CCl4 increased iNOS and TNFalpha mRNA, while N. sativa oil administration for one week prior to CCl4 injection downregulated the CCl4-induced iNOS mRNA and up-regulated IL-10 mRNA. These results indicate that N. sativa oil administration has a protective effect against the CCl4-mediated suppression of hepatic CYPs and that this protective effect is partly due to the downregulation of NO production and up-regulation of the anti-inflamnatory IL-10.