To evaluate the cutaneous injury in liver damaged rats by toluene application to the skin, toluene(35mg/㎤) was sequentially applied for 5 days to the dorsal skin of liver damaged rats with $CCl_4$ (6 times ever other day:0.1$m\ell$/100 g body weight-50% $CCl_4$in olive oil). The cutaneous ultrastructural changes were unexoectably not observed in liver from $CCl_4$-treated rats although necrotic liver damage appeared under light microscope. In these animals by the application of toluene to rat skin the cutaneous xanthine oxidase activity was significantly increased(p<0.05), but cytochrome P450 content was not different from that of the control or only $CCl_4$-treated rats. On the other hand, the cutaneous superoxide dismutase and catalase activities in liver damaged animals were significantly respectively(p<0.05, p<0.001), decreased by toluene application to the skin compared with control and especially the former enzyme activity was significantty decreased(p<0.01), compared with that of liver damaged rate rat but glutathione peroxidase, glutathione-S-transferase activities were not significantly different from those of the control or liver damaged rats. Futhermore, the reduced gluathione content of skin was also significantly decreased by toluene application to the liver damaged animals. In conclusion, the great deposits of cerrous peroxide and ultramorphological changes in skin tissue of liver damaged animals by toluene application may be responsible for the oxygen free radical.
This research was conducted to determine the effects of chitosanoligosaccharide on liver poisoning induced by cadmium (Cd). Three groups of mice were used in this research. The first group was only injected with cadmium (5.0 mg/kg; i.p.) (group Cd) and the second one with cadmium and chitosanoligosaccharide (0.5% solution) at the same time (group Cd+Chi). The third one which had already been injeted with chitosanoligosaccharide (0.5% Solution) aweek before (group Ch7+Cd) was used. In order to investigate the inhibitory action of chitosanoligosaccharide on liver damage, enzyme activity in serum, glutathione peroxidase (GSHPx) activity and glutathione reductase (GR) activity were relatively measured. In addition, histological observations were made to determine the morphologic injury of liver tissues. As the result of enzyme activity in serum, the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in chitosanoligosaccharide-injected groups Cd+Chi and Chi7+Cd was lower than in group Cd. GSH-Px activity was sharply increased in groups Cd+Chi and Chi7+Cd compared to group Cd. GR activity was conspicuously decreased in groups Cd+Chi and Chi7+Cd compared to group Cd. As the result of light microscopic observation, liver cell necrosis caused by cadmium poisoning was obseved in liver cells. The finding of group Cd+Chi and Chi7+Cd was similar total on of normal groups. As the result of electron microscopic observation, mitochondria in group Cd showed a severe swelling phenomenon, RER fragment and ribosome dropout. However, in groups Cd+Chi and Chi7+Cd, mitochondria wiht high electron density were distributed and RER forming a typical lamellae with ribosome was observed. From these results, cadmium toxicity on rat liver tissues could be lessened by chitosanoligosaccharide.
Inhibitory effects of the methanol extract, hexane extract, methanol soluble fraction (MSF) and juice from 3 weeks fermented Kimchi on the tumor formation in sarcoma-180 cell transplanted mice were studied. Effects of the solvent extracts and juice of the Kimchi on the levels of lipid peroxide, glutathione, and the enzyme activities of the liver were also investigated in normal and sarcoma-180 cell transplanted mice. At 32 days following trans-plantation, MSF reduced the tumor formation by 54% compared with the control group, resulting in the smallest tumor weight. Lipid peroxided content in liver increased by the transplantation of sarcoma-180 cells. However, it decreased when MSF of Kimchi was treated to the mice. MSF also suppressed xanthine oxidase activity in cytosol of the liver cells in mice transplanted by sarcoma-180 cells. Kimchi extracts had no inhibitory effect on hepatic aminopyrine-N-demethylase activity in sarcoma-180 cell transplanted or normal mice. Methanol extract and hexane extract of Kimchi slightly increased hepatic glutathione contents in sarcoma-180 treated mice. The injection of MSF from Kimchi markedly increased glutathione levels in the liver of sarcoma-180 treated mice. The injection of MSF from Kimchi markedly increased glutathione levels in the liver of sarcoma-180 treated mice compared to the controls. The MSF recovered the activities of hepatic glutathione reductase and glutathione S-transferase that decreased by the injection of sarcoma-180 cells. These results showed that MSF of Kimchi could suppress the growth of tumors, inhibiting lipid peroxide production and xanthine oxidase activity, in mice. We also suggested that Kimchi extract might play an important role in the prevention of cancer by enhancement of the glutathione level itself as well as via glutathione reductase and glutathione S-transferase.
We assessed the effect of Se-methylselenocysteine (MSC) treatment, at a dose of 0.75 mg/rat/day for 1 or 2 weeks, on the activities of antioxidant systems in Sprague-Dawley rat tissues. Significant changes in glutathione and antioxidant enzyme activities, with different patterns among tissues, were evidenced. Glutathione content and its reduction state in the liver, lung, and kidney were elevated upon MSC treatment, whereas they were significantly lowered in the spleen. Among the tissues exhibiting glutathione increase, there were different enzymatic responses: $\gamma$-glutamylcysteine ligase activity, the rate-limiting enzyme in the glutathione synthesis pathway, was increased in the liver, whereas the activities of the enzymes associated with glutathione recycling, namely, glutathione peroxidase, glutathione reductase, and glucose 6-phosphate dehydrogenase, were significantly increased in the lung and the kidney. The superoxide dismutase activity was decreased in all tissues upon MSC treatment, whereas catalase activity was increased in all tissues but the liver. Lipid peroxidation level was transiently increased at 1 week in the lung and the kidney, whereas it was persistently increased in the spleen. The increase was not evident in the liver. The results indicate that the MSC treatment results in an increase in the antioxidant capacity of the liver, lung, and kidney principally via an increase in glutathione content and reduction, which appeared to be a result of increased synthesis or recycling of glutathione via tissue-dependent adaptive response to oxidative stress triggered by MSC. The spleen appeared to be very sensitive to oxidative stress, and therefore, the adaptive response could not provide protection against oxidative damage.
This work was conducted to investigate the effect of bisphenol A (BPA) on estradiol (E2) 2-and 4-hydroxylase activities in the liver, kidney and lung tissues of male and female rats. After intraperitoneal administration of BPA to male and female rats for 4 days at 0, 10, and 50 mg/kg, the conversion of the substrate for hepatic and extra-hepatic enzyme activities was measured by GC/MSD. The result showed decreases of body and organ weights at 50 mg/kg BPA of male and female rats. Male hepatic E2 2-hydroxylase activity was inhibited by 68% at 10 mg/kg and by 82% at 50 mg/kg BPA. Female hepatic E2 2-hydroxylase activity was decreased by 46% at 10 mg/kg and by 56% at 50 mg/kg to the control. E2 4-hydroxylase was inhibited by 57 and 57% at 10 mg/kg and 54 and 78% at 50 mg/kg in liver of female and male, respectively. The urinary excretion rate of 2-hydroxyestradiol (2-OHE), androsterone and testosterone in urine of female rats with 50 mg/kg BPA were decreased significantly. The results showed that 50 mg/kg BPA was decreased E2 2-and 4-hydroxylase activities in liver, but not in other tissues. The urinary excretion rates of 2-OHE, androsterone and testosterone were also decreased. In liver, estrogenic enzyme activity were higher in male than female. These results suggest that BPA can disrupt estrogen metabolism by suppressing E2 2-and 4-hydroxylase activities in the liver of male and female rats.
This study investigated the effect of dietary $\beta$-carotene supplementation on lipid peroxidation and anti oxidative enzyme activity as indices of oxidative stress in diabetic rats. Fifty Sprague-Dawley male rats aging 7 weeks were used as experimental animals, which were divided into the non-diabetic control group and the diabetic group. The diabetic group received an intraperitoneal injection with streptozotocin to induce diabetes. Then the diabetic rats were divided into four dietary groups which contained different amounts of $\beta$-carotene; 0%, 0.002%, 0.02%, or 0.2% of the diet. The diabetic rats were fed the experimental diets and the non-diabetic rats were fed the basal diet without $\beta$-carotene supplementation for 2 weeks and then sacrificed. The diabetic group had a significantly higher blood glucose level than the non-diabetic group. However, blood glucose level were not significantly changed by the level of dietary $\beta$-carotene supplementation. Compared to the non-diabetic control group, the diabetic control group indicated a significant increase of plasma thiobarbituric acid reactive substance (TBARS). Liver TBARS level also tended to be higher in diabetic control group, although it was not significant. The $\beta$-carotene supplementation did not reduce plasma TBARS level. However, Liver TBARS level was significantly decreased when 0.02% or more $\beta$-carotene was supplemented in the diet. The liver lipofuscin level in the diabetic control group was higher than in the non-diabetic control group, but the effect of $\beta$-carotene supplementation did not show any differences. Superoxide dismutase activity was significantly lower in the diabetic group, but it was increased in groups receiving 0.02% or more $\beta$-carotene. Compared to the non-diabetic control group, lower activities of catalase and glutathione peroxidase were observed in the diabetic control group, although it was not significant. Catalase and glutathione peroxidase activities tended to increase as the levels of $\beta$-carotene supplementation increased, although it was not statistically significant. Therefore, it seems that dietary $\beta$-carotene supplementation might reduce diabetic complications by partly decreasing the lipid peroxidation and increasing the activity of antioxidative enzyme in diabetes.
Objectives: The aim of this study was to investigate the influence of five herbal medicines on cytochrome P450 (CYP) 3A4 drug-metabolizing enzymes in human liver microsomes. Methods: By using of human liver microsomes, we extracted Cnidium officinale Makino, Rhus verniciflua Stokes, Prunus persica Batsch, Corydalis remota Fisch, Carthamus tinctorius Linne, which are called Hwalhyulgeoouhyak(活血祛瘀藥). Then they were incubated and measured for relative enzyme activity under incubation conditions compared to ketoconazole, which is known as a representative inhibitor of CYP 3A4. Results: We showed that all of five traditional herbal medicines had no inhibition effect of CYP 3A4 at 10, 20, 30, 40, and 50${\mu}g/m{\ell}$ doses in human liver microsomes, although Rhus verniciflua Stokes (RVS) showed a little inhibition as about 95% enzyme activity of control. However, this result was not enough to prove that RVS has a CYP 3A4 inhibition effect. Moreover, we can't confirm that those rates have significant induction effect on CYP 3A4. Conclusions: The result of this study could support that those herbal medicines are more reliable than chemical drugs, even if this is a basic step to prove that result.
Sea-urchins (Anthocidaris crassispina) are widely distributed in the East Sea of Korea. The aim of this study was to evaluate the hepatoprotective effects of sea-urchin roe on bromobenzene (BB)-induced liver damage in rats. The antioxidative and detoxifying properties of sea-urchin roe in BB-poisoned rat liver was examined by chemical analysis of serum aminotransferase (AST, ALT), glutathione S-transferase (GST), $\gamma$-glutamylcystein synthetase, glutathione reductase, epoxide hydrolase, amino-N-demethylase (AD), aniline hydrolase (AH) enzyme activity, as well as lipid peroxide and glutathione contents. Sea-urchin roe inhibited the increase of serum AST, ALT enzyme activity. Increasing lipid peroxide contents and AD and AH activities were significantly decreased in ethanol extract of sea-urchin roe. GST, $\gamma$-glutamylcystein synthetase, glutathione reductase and epoxide hydrolase enzyme activities increased in sea-urchin roe-fed group, compared with the BB-treated group. These results suggest that sea-urchin roe facilitates recovery from liver damage by enhancing antioxidative defense mechanisms and hepatic detoxication metabolism.
The overall purpose of this study was to investigate the effects of Chunggukjang and Greentea-Chunggukjang on the lipid profile, lipid peroxidation and antioxidative enzyme activities of liver tissue in growing male rats fed cholesterol. Twenty seven rats were divided into three treatment groups (Control, Chunggukjang and Greentea-Chunggukjang) and were given experimental diets with 1% cholesterol for 9 weeks. All rats in this study were fed a casein-based diet. Chunggukjang groups were fed diet containing 33.1% Chunggukjang powder. The Chunggukjang and Greentea-Chunggukjang groups showed significantly lower weight gain, food efficiency ratio than the control group regardless of Chunggukjang type. Serum total cholesterol was significantly lower in the Chunggukjang group than in the control group, whereas serum triglyceride and atherogenic index were significantly lower in the Greentea-Chunggukjang group than in the control group. Hepatic triglyceride contents was not significantly different among the diets. However, hepatic cholesterol content was significantly lower in the Greentea-Chunggukjang group than in the control group. Lipid peroxidation of malondialdehyde (MDA) contents was significantly lower in the Chunggukjang and Greentea-Chunggukjang groups than in the control group. Activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in liver tissue of the Chunggukjang and Greentea-Chunggukjang groups were not significantly different. It can be concluded that Chunggukjang and Greentea-Chunggukjang influence lipid profile and hepatic malondialdehyde contents in growing male rats fed cholesterol.
The enzyme activities and antioxidative of tocopherol and ascorbate were investigated at the levels of liver, kidney homogenates and sera of SD-rats intoxicated with tetrachlorocarbon$CCl_4$. GOT and GPT activities of sera in the $CCl_4$ group were 3, 6 times increased compared to normal group. But they tended to decrease significantly in tocopherol and ascorbate administered group. As for BUN and total cholesterol they were the same. HDL-cholesterol in the $CCl_4$group was 42% decreased compared to normal group. HDL-cholesterol was about 26% increased in the tocopherol group and tocopherol ascorbate group compared to $CCl_4$ group. MDA and SOD activities in the liver and the kidney tissue homogenates were significantly increased in $CCl_4$ group compared to normal group. But they were decreased significantly in the tocopherol group and tocopherol-ascorbate group compared to $CCl_4$ group. In view of this study tocopherol and ascorbated were ascorbate were effective on the detoxication of liver and kidney injury.
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