• Journal of Microbiology and Biotechnology
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• v.17 no.12
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• pp.1983-1990
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• 2007

Antidiabetic effects of a novel microbial biopolymer (PGB) 1 excreted from new Enterobacter sp. BL-2 were tested in the db/db mice. The animals were divided into normal control, rosiglitazone (0.005%, wt/wt), low PGB1 (0.1%, wt/wt), and high PGB1 (0.25%, wt/wt) groups. After 5 weeks, the blood glucose levels of high PGB1 and rosiglitazone supplemented groups were significantly lower than those of the control group. In hepatic glucose metabolic enzyme activities, the glucokinase activities of PGB1 supplemented groups were significantly higher than the control group, whereas the PEPCK activities were significantly lower. The plasma insulin and hepatic glycogen levels of the low and high PGB1 supplemented groups were significantly higher compared with the control group. Specifically, the insulin and glycogen increases were dose-responsive to PGB1 supplement. PGB1 supplement did not affect the IPGTT and IPITT compared with the control group; however, rosiglitazone significantly improved IPITT. High PGB1 and rosiglitazone supplementation preserved the appearance of islets and insulin-positive cells in immunohistochemical photographs of the pancreas compared with the control group. These results demonstrated that high PGB1 (0.25% in the diet) supplementation seemingly contributes to preventing the onset and progression of type 2 diabetes by stimulating insulin secretion and enhancing the hepatic glucose metabolic enzyme activities.

• Molecules and Cells
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• v.46 no.8
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• pp.496-512
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• 2023

A fructose-enriched diet is thought to contribute to hepatic injury in developing non-alcoholic steatohepatitis (NASH). However, the cellular mechanism of fructose-induced hepatic damage remains poorly understood. This study aimed to determine whether fructose induces cell death in primary hepatocytes, and if so, to establish the underlying cellular mechanisms. Our results revealed that treatment with high fructose concentrations for 48 h induced mitochondria-mediated apoptotic death in mouse primary hepatocytes (MPHs). Endoplasmic reticulum stress responses were involved in fructose-induced death as the levels of phosho-eIF2α, phospho-C-Jun-N-terminal kinase (JNK), and C/EBP homologous protein (CHOP) increased, and a chemical chaperone tauroursodeoxycholic acid (TUDCA) prevented cell death. The impaired oxidation metabolism of fatty acids was also possibly involved in the fructose-induced toxicity as treatment with an AMP-activated kinase (AMPK) activator and a PPAR-α agonist significantly protected against fructose-induced death, while carnitine palmitoyl transferase I inhibitor exacerbated the toxicity. However, uric acid-mediated toxicity was not involved in fructose-induced death as uric acid was not toxic to MPHs, and the inhibition of xanthine oxidase (a key enzyme in uric acid synthesis) did not affect cell death. On the other hand, treatment with inhibitors of the nicotinamide adenine dinucleotide (NAD)⁺-consuming enzyme CD38 or CD38 gene knockdown significantly protected against fructose-induced toxicity in MPHs, and fructose treatment increased CD38 levels. These data suggest that CD38 upregulation plays a role in hepatic injury in the fructose-enriched diet-mediated NASH. Thus, CD38 inhibition may be a promising therapeutic strategy to prevent fructose-enriched diet-mediated NASH.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.1
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• pp.40-45
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• 2013

This study was designed to examine the effect of sea buckthorn (SBT) leaves on hepatic antioxidative enzyme levels in diabetic rats. Diabetes mellitus was induced in male Sprague-Dawley rats by an injection of streptozotocin (STZ). Sprague-Dawley rats were then fed for four weeks, with experimental groups receiving a modified diet containing 10% or 20% powder derived from SBT leaves. The experimental groups were divided into six groups: a normal (N)-control group, N-SBT 10% and N-SBT 20% treated groups, STZ-control, STZ-SBT 10% and STZ-SBT 20% treated groups. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione-S-transferase (GST) and xanthine oxidase (XOD) levels were measured in liver cytosol. The results showed that the level of SOD was significantly increased in the N-SBT 20% group but not statistically different in the diabetic group. The level of CAT was significantly higher in the N-SBT 20% group compared to the control group. The level of GPX was significantly increased in the N-SBT 20% group and the diabetic supplementary group. In contrast, the level of XOD was significantly decreased in the diabetic group supplemented with SBT leaves.

• Proceedings of the Ginseng society Conference
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• 1988.08a
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• pp.81-86
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• 1988

The effect of three polyacetylene compounds. panaxydol. panaxynol and panaxytriol isolated from Korean ginseng on $CCI_4-induced$ lipid peroxidation in vitro and in vivo hepatic microsomal lipid peroxidation were investigated. Lipid peroxide levels both in serum and liver and serum enzyme (GOT. GPT. LDH) activities of normal or $CCI_4-treated$ mice and rats were also determined after administration of polyacetylenes. Hepatic microsomal cytochrome P-450 content and activities of aniline hydroxylase and aminopyrine demethylase were measured after treatment of polyacetylenes with or without carbon tetrachloride. As results. treatment with polyacetylenes to control mice did not influence the levels of lipid peroxides and serum enzyme activities while panaxynol did. Panaxynol itself inhibited liver lipid peroxidation in normal mice. Polyacetylene compounds protected hepatic lipid peroxidation and lowered serum lipid peroxide levels induced by $CCI_4$ Polyacetylenes prevented leakage of LDH to serum but elevated GOT and GPT levels caused by $CCI_4$ were not changed by polyacetylene pretreatment. $CCI_4$ caused losses in the content of cytochrome P-450 and activities of aniline hydroxylase and aminopyrine demethylase. When polyacetylenes were treated without $CCI_4$ panaxydol and panaxynol induced aniline hydroxylase and all three polyacetylenes induced aminopyrine demethylase. Cytochrome P-450 contents were not affected by polyacetylenes. In vitro hepatic microsomal lipid peroxidation was inhibited by polyacetylenes and $DL-{\alpha}-tocopherol$ in a concentration-dependent manner.

• Preventive Nutrition and Food Science
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• v.1 no.2
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• pp.214-219
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• 1996

This study was done to investigate effects of n-s fatty acids and vitamin E supplement on the preneoplastic hepatic enzyme altered foci and cholesterol metabolism in experimental hepatocarcinogenesis system. Weaning male Sprague-Dawley rats were fed the diet containing either 15% corn oil(CO) or sardine oil(SO) with or without vitamin E 800IU supplementation for 12 weeks. After two weeks of feeding, rats were intraper-itoneally injected with a single dose of diethylnitrosamine(DEN:200mg/kg, BW). At the 4th week, rats were given the diet containing 0.02% acetylaminofluorene(AAF) for next 4 weeks. At the 6th Week, 0.05% pheno-barbital was incorporated into diet for 6 weeks. At the end of 12th week, rats were sacrificed and hepatic glutathions S-transferase placental form positive(GST_{TEX}$P^{+}${/TEX}) foci and serum and liver cholesterol levels were determined. GST_{TEX}$P^{+}${/TEX} formation was significantly decreased by SO feeding when compared with Co feeding but it tended to be enhanced by vitamin E supplementation. Histopathological changes were similar to patterns of GST_{TEX}$P^{+}${/TEX} formation in almost all dietary groups. Serum and hepatic cholesterol levels of SO fed groups were significantly lower than those of CO fed groups. Carcinogen treatments significantly increased serum and liver cholesterol levels in CO fed groups but not in SO fed groups. Correlation data showed a positive correlation(${\gamma}$=0.83, p<0.01) between serum cholesterol level GST_{TEX}$P^{+}${/TEX} foci area. These results indicate that sardine oil as a m-3 fatty acid source may have a reducing effect in rat hepatocarcinogenesis by the altheration of cholesterol metabolism.

• Nutrition Research and Practice
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• v.18 no.1
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• pp.46-61
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• 2024

BACKGROUND/OBJECTIVES: An increasing life expectancy in society has burdened healthcare systems substantially because of the rising prevalence of age-related metabolic diseases. This study compared the effects of animal protein hydrolysate (APH) and casein on metabolic diseases using aged mice. MATERIALS/METHODS: Eight-week-old and 50-week-old C57BL/6J mice were used as the non-aged (YC group) and aged controls (NC group), respectively. The aged mice were divided randomly into 3 groups (NC, low-APH [LP], and high-APH [HP] and fed each experimental diet for 12 weeks. In the LP and HP groups, casein in the AIN-93G diet was substituted with 16 kcal% and 24 kcal% APH, respectively. The mice were sacrificed when they were 63-week-old, and plasma and hepatic lipid, white adipose tissue weight, hepatic glucose, lipid, and antioxidant enzyme activities, immunohistochemistry staining, and mRNA expression related to the glucose metabolism on liver and muscle were analyzed. RESULTS: Supplementation of APH in aging mice resulted in a significant decrease in visceral fat (epididymal, perirenal, retroperitoneal, and mesenteric fat) compared to the negative control (NC) group. The intraperitoneal glucose tolerance test and area under the curve analysis revealed insulin resistance in the NC group, which was alleviated by APH supplementation. APH supplementation reduced hepatic gluconeogenesis and increased glucose utilization in the liver and muscle. Furthermore, APH supplementation improved hepatic steatosis by reducing the hepatic fatty acid and phosphatidate phosphatase activity while increasing the hepatic carnitine palmitoyltransferase activity. Furthermore, in the APH supplementation groups, the red blood cell (RBC) thiobarbituric acid reactive substances and hepatic H₂O₂ levels decreased, and the RBC glutathione, hepatic catalase, and glutathione peroxidase activities increased. CONCLUSIONS: APH supplementation reduced visceral fat accumulation and alleviated obesity-related metabolic diseases, including insulin resistance and hepatic steatosis, in aged mice. Therefore, high-quality animal protein APH that reduces the molecular weight and enhances the protein digestibility-corrected amino acid score has potential as a dietary supplement for healthy aging.

• Journal of Nutrition and Health
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• v.40 no.8
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• pp.701-707
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• 2007

This study was to investigate lipid peroxidation, antioxidant enzyme activity and DNA damage after exercise, and the protective effect of garlic against exercise-induced oxidative stress. Male Sprague-Dawley rats(4 weeks old) were randomly divided into three groups of 6 rats each; control group(Con) without garlic and exercise, Ex group with exercise alone, and Ex-G group with 2% garlic and exercise. For 4 weeks, rats were given diets containing 15% corn oil and 1% cholesterol with or without garlic. The swimming was selected as a model for exercise performance. Rats swam for 40 min a day, for 5 days a week. Group Ex and Ex-G showed significant lowering in body weight gain and fat accumulation compared to control. No significant changes were observed in levels of plasma cholesterol and triglyceride among three groups, demonstrating that exercise and garlic had no effects on changes of blood lipid. This finding of blood lipid seems to be due to higher plant sterol content in corn oil. The DNA tail moment of lymphocytes showed greater tendency in Ex and Ex-G than in control, but garlic supplements failed to suppress DNA damages. Compared to control, Ex had higher plasma TBARS which was lowered to the control's level in Ex-G with 2% garlic supplementation(p<0.05). Ex-G led to a higher hepatic superoxide dismutase(SOD) activity than control and Ex(p<0.05). Activity of hepatic catalase was also increased in Ex-G, while in Ex it was significantly low(p<0.05). It seemed that TBARS levels were related to the activities of SOD and catalase, and that garlic contributed to increasing the enzyme activities and led to decrease of TBARS. These results demonstrate that lipid peroxidation and DNA damage occur as a consequences of oxidative stress after exercise, and that antioxidant defense against oxidative stress could be enhanced by garlic supplementation through the induction of antioxidant enzymes. However, further investigations should be done on the garlic effect on DNA damage.

• Journal of Nutrition and Health
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• v.39 no.1
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• pp.3-10
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• 2006

Effects of garlic powder supplementation on blood lipid profile and antioxidant system were investigated in rats with and without swimming exercise. Sprague-Dawley rats of four experimental groups were fed for 4 weeks diets containing $15\%$ beef tallow and $1\%$ cholesterol; control without garlic and exercise, Go with $2\%$ garlic alone, Ex with exercise alone, GoEx with $2\%$ garlic and exercise. Rats were trained 40 min a days a days a week. Group Ex and GoEx showed significant lowering in body weight gain and fat accumulation. In Go, Ex and GoEx, plasm TG and LDL-C were lower and HDL-C was higher, although not significantly, compared to levels in control. Total cholesterol was significantly reduced in group Go, and Ex and GoEx were lower than control. The total/HDL cholesterol ratio was also found to be significantly different, decreasing the ratios in Go, Ex and GoEx. The hepatic TBARS increased significantly in group Ex $(51.7{\pm}3.43nM/g\;liver)$, while TBARS in Go and GoEx were low $(35.68{\pm}3.61,\;39.30{\pm}5.55nM/g\;liver)$ and similar to control's one. The activity of hepatic SOD in Go and GoEx tended higher than control and Ex without garlic. The hepatic catalase showed significantly the highest activity in Go. Activity of GSH-px was significantly low in Ex with $0.14{\pm}0.03$ unit/mg protein, and control, Go and GoEx had higher activities of $0.23{\pm}0.08,\;0.20{\pm}0.07,\;0.22{\pm}0.01\;unit/mg$ protein, respectively. Lower activities of antioxidant enzymes in Ex are likely to associated with the highest level of TBARS. It seems that a decrease in TBARS in GoEx relative to Ex was related to the increase in GSHpx and SOD with garlic supplemented, which led to compensate the oxidative stress from exercise. The results suggests that exercise or garlic supplement exerts blood lipid attenuating effect. In adition, garlic supplementation could strengthen the antioxidant potential against exercise-induced oxidants, partly by modulating oxidant enzyme activity. These effects of garlic may make it a beneficial agent on CVD.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.17 no.3
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• pp.162-169
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• 2014

Purpose: To study temporal pattern of serum liver enzymes levels in newborns with hepatic injury associated with birth asphyxia (BA). Methods: Singleton term newborns with BA and ${\leq}72$ hours of age admitted to neonatal intensive care unit were prospectively enrolled. Term newborns with physiological jaundice and without BA were studied as controls. Serum liver enzymes were measured at <24 hours, 24-72 hours, and at 6-12 days of age for cases and at 1-6 days of age for controls. BA was defined by 1 minute Apgar score <7 or delayed or absent cry with hypoxic ischemic encephalopathy. BA-associated liver injury was defined as serum alanine aminotransferase (ALT) elevation beyond +2 standard deviation (ALT > +2 SD) above the mean of control subjects at any of the three time points. Results: Sixty controls and 62 cases were enrolled. Thirty-five cases (56%) developed BA-associated liver injury (ALT>81 IU/L). They had higher serum levels of ALT, aspartate aminotransferase, lactate dehydrogenase than the control infants, with peak at 24-72 hours. In controls, serum liver enzyme levels were significantly higher in appropriate-for-date (AFD) babies than small-for-date (SFD) babies. Serum enzyme pattern and extent of elevation were comparable between SFD and AFD babies. Degree of serum liver enzyme elevation had no relationship with severity of hypoxic encephalopathy. Conclusion: Serum liver enzyme elevation is common in BA; it peaks at 24-72 hours followed by a sharp decline by 6-12 days of age. Pattern and extent of enzyme elevation are comparable between SFD and AFD babies.

• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.126-133
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• 2006

Thioacetamide (TA) is well known hepatotoxic and hepatocarcinogenic agent. TA also diminishes the contents of hepatic cytochrome P450 and inhibits the enzyme activity of the hepatic mixed function oxidases. TA metabolite, thioacetamide-s-oxide, is further transformed into a still unknown highly reactive metabolite that binds to macromolecules. In this study, we focused on TA-induced gene expression at hepatotoxic dose. Mice were exposed to two levels (5 mg/kg or 50 mg/kg i.p.) of TA, sampled at 6 or 24 h, and hepatic gene expression levels were determined to evaluate dose and time dependent changes. We evaluated hepatotoxicity by serum AST and ALT level and histopathological observation. Mean serum activities of the liver leakage enzymes, AST and ALT, were slightly increased compare to control. H & E and PAS evaluation of stained liver sections revealed TA-associated histopathological finding in mice. Centrilobular eosinophilic degeneration was observed at high dose-treated mice group. Hepatic gene expression was analyzed by QT clustering. Clustering of high dose-treated samples with TA-suggests that gene expressional changes could be associated from toxicity as measured by traditional biomarkers in this acute study.