Hepatic Lipid Peroxidation Levels Research Articles

Effect of Ascorbic Acid on Antioxidant Defense Systems and Lipid Peroxidation in Guinea Pig

In view of the antioxidant properties of ascorbic acid (AA), effects of inadequate and excessive doses of AA on hepatic and pulmonary antioxidant enzymes and NADPH-dependent lipid peroxidation were investigated in the present study. Male guinea pigs, dosed daily with 0.2mg AA/100g b wt (inadequate) or 50mg AA/100g b wt (excessive) for 8 weeks, demonstrated no difference in body growth, liver and lung weights, and post-10, 000×g supernatant protein contents as compared with the control group, which was daily fed with 2mg AA/ 100g b wt. Inadequacy of AA decreased the hepatic and pulmonary contents of catalase, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), but it significantly increased glutathione reductase (GR) activity (p<0.005) in lung. However, levels of hepatic and pulmonary NADPH-dependent lipid peroxidation remained unaltered when the supply of AA was inadequate. Excessive doses of AA did not influence any pulmonary antioxidant enzyme, level of NADPH-dependent lipid peroxidation and content of reduced glutathione (GSH), but increased the hepatic GSH-Px and GR activities. Hepatic SOD activity showed a significant decrease (p<0.01), whereas NADPH-dependent lipid peroxidation and GSH contents remained unchanged. It appears that the changes in antioxidant enzymes may be a nonspecific response to AA or these changes may not be sufficient to bring about any shift in the levels of NADPH-dependent lipid peroxidation in the presence of unaltered GSH contents or other biomolecules which may act as antioxidants or free radical scavengers in the cell system.

Effect of cadmium chloride on hepatic lipid peroxidation in mice.

Intraperitoneal administration of cadmium chloride to 8-12 weeks old CBA-mice enhanced hepatic lipid peroxidation. A positive correlation between cadmium chloride dose and level of peroxidation was observed in both male and female mice. A sex-related difference in mortality was not observed but at a dose of 25 mumol CdCl2/kg the level of hepatic lipid peroxidation was higher in male mice than in female mice. The hepatic lipid peroxidation was not increased above the control level in 3 weeks old mice, while 6 weeks old mice responded with increased peroxidation as did 8-12 weeks old mice. The mortality after an acute toxic dose of cadmium chloride was the same in the three age groups. Pretreatment of mice with several low intraperitoneal doses of cadmium chloride alleviated cadmium induced mortality and lipid peroxidation. The results demonstrate both age dependency and a protective effect of metallothionein induction on cadmium chloride induced hepatic lipid peroxidation.

Hepatic lipid peroxidation and intracellular calcium accumulation in ethanol potentiated aflatoxin B1 toxicity.

The possible role of hepatic lipid peroxidation and Ca2+ in enhanced hepatotoxicity of aflatoxin B1 (AFB1) by ethanol was examined along with changes in hepatic glutathione in male rats. Hepatic glutathione (GSH) was markedly decreased (43.9%) at 12 h after AFB1 administration in rats treated with ethanol (4.0 g/kg BW) and AFB1 (2.0 mg/kg BW) when compared to AFB1 alone. At 24 h after AFB1 administration, hepatic lipid peroxide levels in subcellular fractions, particularly in microsomes, were significantly increased (76.9%) in rats treated with ethanol and AFB1 following the decrease in hepatic GSH content. Hepatic lipid peroxide levels returned to normal values at about 48 h after AFB1 administration. Furthermore, Ca2+ in whole liver (60.9%), microsomes (83.8%) and mitochondria (51.2%) were significantly increased in the rats treated with ethanol and AFB1 as compared to those rats treated with AFB1 alone at 48 h after toxin administration. The increase in hepatic Ca2+ in rats treated with ethanol and AFB1 was a possible consequence of the increase in hepatic lipid peroxide. These findings suggest that there is a close relationship between hepatic GSH content, lipid peroxidation and intracellular accumulation of Ca2+. The pronounced effects on hepatic lipid peroxidation and intracellular accumulation of Ca2+ could play a role in ethanol-induced potentiation of AFB1 hepatotoxicity in rats.

Stimulation of lipid peroxidation and impairment of glutathione-dependent defence system in the liver of rats repeatedly treated with carbon tetrachloride.

To study the effect of carbon tetrachloride treatment on hepatic lipid peroxidation and glutathione-dependent defence system, rats were injected with carbon tetrachloride (0.2 ml/kg body weight, i.p.) twice weekly for a period of 4 weeks. Carbon tetrachloride treatment caused a significant increase in hepatic lipid peroxide levels and significant decreases in hepatic glutathione levels and glutathione peroxidase and glutathione transferase activities. These results show that chronic carbon tetrachloride administration to rats leads to the stimulation of hepatic lipid peroxidation, which seems to be the consequence of impaired cellular defence by glutathione and glutathione-related enzymes.

食じ中のメチオニンがクロロベンゼン投与によって生じたラット肝グルタチオンおよび過酸化脂質レベルの変化に与える影響

クロロベンゼンの毒性とクロロベンゼンによって惹起される代謝応答が, 食餌中のメチオニン含量の変化によってどのように修飾されるかを検討した。ラットを2群に分け, 10%カゼイン飼料 (基本飼料) および0.3%のDL-メチオニンを補足した10%カゼイン飼料で4週間飼育した後, 0, 0.2, 0.5, または2.0mmol/kg body weightのクロロベンゼンを腹腔内投与した。基本飼料群ラットにおいては, 0.5mmol/kgのクロロベンゼン投与によって肝TBA値が有意に上昇し, 2.0mmol/kgの投与では6匹中4匹が投与後48時間以内に死亡した。飼料へのメチオニン補足は, 肝TBA値の上昇を軽減し, 全ラットを生存させるとともに, 0.5mmol/kg以上の投与の場合に肝湿重量の有意な増大を生じさせた。また基本飼料群では, メチオニン補足飼料群に比して肝グルタチオン合成活性が有意に高いにもかかわらず, 低い肝グルタチオン濃度しか認められず, クロロベンゼン投与48時間後のグルタチオン濃度にも変化がなかった。しかし, メチオニン補足飼料群においては, 肝グルタチオン合成はクロロベンゼン投与によって亢進し, 肝グルタチオン合成活性とグルタチオン濃度の上昇が生じた。以上の結果より, 10%カゼイン食という含硫アミノ酸の少ない食餌条件下においては, 肝グルタチオン合成系よりのシステイン要求が充足されていないために, クロロベンゼンのような肝グルタチオンを消費する化合物を負荷した場合に, 過酸化脂質生成にもとづく重大な障害の発生する可能性があると判断された。

Alteration of hepatic lipidperoxide levels during cataract formation caused by glucocorticoids in developing chick embryos

The level of hepatic lipidperoxides in chick embryos was determined during cataract formation resulting from glucocorticoid treatment. When 15 day old chick embryos were administered 0.25 μmol of hydrocortisone acetate their hepatic lipidperoxide level, determined by thiobarbituric acid, increased after a lag time of 20 hr and reached approximately 8-fold of control at 48 hr after the treatment. These studies indicate that the peroxidation of lipid in tissues should be considered in elucidating mechanisms of action or adverse effects of glucocorticoids.

Hepatic lipid peroxidation and mitochondrial susceptibility to peroxidative attacks during ethanol inhalation and withdrawal

Male Sprague-Dawley rats were exposed to increasing concentrations (15–22 mg/l) of ethanol vapor over a 4-day period. The hepatic lipid peroxide level as well as the sensitivity of mitochondria and microsomes to peroxidative attacks were studied during the early stage of alcohol intoxication, at the end of the inhalation period and, finally, during withdrawal. The level of hepatic lipid peroxide started to increase significantly after the first day of ethanol inhalation, whereas the in vitro mitochondrial sensitivity to peroxidation induced by ADP · Fe 3+ in the presence of an O 2 −-generating system was still unaltered after a 2-day inhalation period. Both the hepatic peroxide level and the mitochondrial sensitivity to peroxidation were significantly enhanced at the end of the 4-day inhalation period. Such an enhancement was still apparent 24 h after withdrawal, a time at which no more ethanol was present in the blood. Lipid peroxidation returned to normal values only 48 h after withdrawal. Microsomes were less affected than mitochondria by the ethanol treatment. It is suggested that the alterations of lipid peroxidation are related to the presence and/or the metabolism of ethanol at an early stage of inhalation, whereas changes in the membrane structure would be responsible for the maintenance of enhanced lipid peroxidation 24 h after ethanol withdrawal.

Therapeutic effect of taurine administration on carbon tetrachloride-induced hepatic injury.

To determine the therapeutic efficacy of taurine administration on liver injury, the effect of taurine on hepatic lipid peroxide level following carbon tetrachloride (CCl4) administration was investigated. To CCl4 intoxicated rats (CCl4, 2 ml/kg, i.p.), 3 ml of a 10% aqueous solution of taurine was administered after CCl4 administration (at 12, 16, and 20 hr after), and rats were sacrificed at 24 hr after CCl4 administration in order to estimate the level of lipid peroxides in the liver. The decrease of hepatic lipid peroxidation induced by CCl4 was noticed in the taurine-treated rats. Taurine had no effect on mixed function oxidase activity in hepatic microsomes as well as no effect on hepatic antioxidant content in the CCl4-intoxicated rats. Hepatic taurine content decreased significantly 12 and 24 hr after CCl4 administration, whereas oral administration of taurine to CCl4-intoxicated rats was able to protect these rats from hepatic taurine depletion. These results suggest that hepatic taurine may play a critical role on the protection of hepatocytes against hepatotoxins such as CCl4 and the administration of taurine may be useful in the treatment of hepatotoxin-induced liver injury.

THERAPEUTIC EFFECT OF TAURINE ADMINISTRATION ON CARBON TETRACHLOR1DE-INDUCED HEPATIC INJURY

AbstractTo determine the therapeutic efficacy of taurine administration on liver injury, the effect of taurine on hepatic lipid peroxide level following carbon tetrachloride (CCl4) administration was investigated. To CCl4 intoxicated rats (CCl4, 2 ml/kg, i.p.), 3 ml of a 10% aqueous solution of taurine was administered after CCl4 administration (at 12, 16.. and 20 hr after), and rats were sacrificed at 24 hr after CCl4 administration in order to estimate the level of lipid peroxides in the liver. The decrease of hepatic lipid peroxidation induced by CCl4 was noticed in the taurine-treated rats. Taurine had no effect on mixed function oxidase activity in hepatic microsomes as well as no effect on hepatic antioxidant content in the CCl4-intoxicated rats. Hepatic taurine content decreased significantly 12 and 24 hr after CCl4 administration, whereas oral administration of taurine to CCl4-intoxicated rats was able to protect these rats from hepatic taurine depletion. These results suggest that hepatic taurine may play a critical role on the protection of hepatocytes against hepatotoxins such as CCl4 and the administration of taurine may be useful in the treatment of hepatotoxin-induced liver injury.