Amelioration of Metal-Induced Cellular Stress by α-Lipoic Acid and Dihydrolipoic Acid through Antioxidative Effects in PC12 Cells and Caco-2 Cells.

α-Lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are endogenous dithiol compounds with significant antioxidant properties, both of which have the potential to detoxify cells. In this study, ALA (250 µM) and DHLA (50 µM) were applied to reduce metal (As, Cd, and Pb)-induced toxicity in PC12 and Caco-2 cells as simultaneous exposure. Both significantly decreased Cd (5 µM)-, As (5 µM)-, and Pb (5 µM)-induced cell death. Subsequently, both ALA and DHLA restored cell membrane integrity and intracellular glutathione (GSH) levels, which were affected by metal-induced toxicity. In addition, DHLA protected PC12 cells from metal-induced DNA damage upon co-exposure to metals. Furthermore, ALA and DHLA upregulated the expression of survival-related proteins mTOR (mammalian target of rapamycin), Akt (protein kinase B), and Nrf2 (nuclear factor erythroid 2-related factor 2) in PC12 cells, which were previously downregulated by metal exposure. In contrast, in Caco-2 cells, upon co-exposure to metals and ALA, Nrf2 was upregulated and cleaved PARP-1 (poly (ADP-ribose) polymerase-1) was downregulated. These findings suggest that ALA and DHLA can counterbalance the toxic effects of metals. The protection of ALA or DHLA against metal toxicity may be largely due to an enhancement of antioxidant defense along with reduced glutathione level, which ultimately reduces the cellular oxidative stress.

Long-term effects of maternal resveratrol intake during lactation on cholesterol metabolism in male rat offspring.

Resveratrol (RSV) can protect against non-communicable diseases by improving cholesterol metabolism. However, it is unclear that effects of maternal RSV intake on health of adult offspring. In this study, we examined effects of maternal RSV intake during lactation on cholesterol metabolism in adult male rat offspring. Female Wistar rats were fed a control diet (CON) supplemented with or without RSV (20 mg/kg body weight/day) during their lactation period. Male offspring were weaned onto a standard diet and maintained on this diet for 36 weeks. As a result, plasma cholesterol level significantly decreased in RSV offspring compared to CON offspring. Furthermore, a decrease in hepatic 3-hydroxy-3-methylglutaryl-CoA reductase level and an increase in hepatic LDL-receptor level were observed in the RSV offspring. These results indicate that maternal RSV intake causes long-term decrease in plasma cholesterol level in the offspring through suppression of hepatic cholesterol biosynthesis and promotion of hepatic cholesterol uptake.

Maternal green tea extract intake during lactation attenuates hepatic lipid accumulation in adult male rats exposed to a continuous high-fat diet from the foetal period.

BACKGROUND: Maternal lipid intake in the early postnatal period has a long-term effect on the possibility of fatty liver formation in children; besides, the importance of lipid consumption during lactation for children's health has been suggested. Green tea extract (GTE) contains abundant catechins, and it has been reported to improve lipid metabolism and prevent fatty liver. OBJECTIVE: The aim of this study was to examine the effects of maternal GTE intake during lactation on hepatic lipid accumulation in adult male rats exposed to a continuous high-fat (HF) diet from the foetal period. METHODS: Pregnant Wistar rats received diets containing 13% (control-fat, CON) or 45% (high-fat, HF) fat. CON-fed mothers received the same diet during lactation, whereas HF-fed mothers received either HF diet alone or HF diet supplemented with 0.24% GTE. At weaning, male offspring were divided into three groups, i.e. CON/CON/CON, HF/HF/HF (HF-offspring) or HF/HF+GTE/HF (GTE-offspring), and were fed until 51 weeks. RESULTS: A significant hepatic triglyceride (Tg) accumulation was observed in the HF-offspring when compared with the other offspring. This is presumed to be caused by the promotion of Tg synthesis derived from exogenous fatty acid due to a significant increase in diacylglycerol O-acyltransferase 1 and a decrease in Tg expenditure caused by decreasing microsomal triglyceride transfer protein (MTTP) and long-chain acyl-CoA dehydrogenase. On the other hand, attenuated hepatic Tg accumulation was observed in the GTE-offspring. The levels of the hepatic lipid metabolism-related enzymes were improved to the same level as the CON-offspring, and particularly, MTTP was significantly increased as compared with the HF-offspring. CONCLUSION: This study indicates the potential protective effects of maternal GTE intake during lactation on HF diet-induced hepatic lipid accumulation in adult male rat offspring and the possible underlying mechanisms.

Polyphenol-enriched azuki bean (Vina angularis) extract reduces the oxidative stress and prevents DNA oxidation in the hearts of streptozotocin-induced early diabetic rats.

We examined the changes in the heart of rats at the early stages of streptozotocin (STZ)-induced diabetes, and whether azuki bean extract (ABE) could influence these changes. The experimental diabetic rats received 0 or 40 mg/kg of ABE orally for 4 weeks, whereas the control group rats received distilled water. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and expression of proteins associated with peroxisomal FA ß-oxidation as well as oxidative stress markers were examined. The levels of peroxisomal ACOX1 and catalase of the diabetic groups were significantly higher than those in the control group. The levels of p62, phosphorylated-p62 (p-p62) and HO-1 in the STZ group were significantly higher than those in the control group, and the levels of p-p62, HO-1, and 8-OHdG were significantly lower by ABE administration. The STZ-induced early diabetes increases the levels of proteins related to peroxisomal FA ß-oxidation and oxidative stress markers in hearts. ABE protects diabetic hearts from oxidative damage.

Elucidation of the mechanism of changes in the antioxidant function with the aging in the liver of the senescence-accelerated mouse P10 (SAMP10).

Senescence-accelerated mice are known to display a variety of deficits and signs of accelerated aging, but the specific mechanisms involved in this process are still unclear. In this study, we examined the expression levels of antioxidant enzymes, transcription factors responsible for the regulation of expression of these enzymes, and mitochondrial proteins in the liver of SAMP10 and SAMR1 mice at 3 and 12 months of age using western blotting analysis. To investigate the amount of oxidative damage to DNA, levels of 8-OHdG were measured in the liver of these mice. At 3 months of age, the levels of catalase, Mn-SOD, GPx, UQCRC2 and COXIV were significantly upregulated in SAMP10 mice compared with that in SAMR1 mice. However, NDUFS3 levels were not significantly different at this young age. In contrast, the expression level of catalase was significantly lower, and the levels of phosphorylated FoxO-1a and UQCRC2 were significantly higher in SAMP10 mice compared to those in SAMR1 mice; however, at 12 months of age, there were no significant differences in Mn-SOD, GPx, total -FoxO-1a, COXIV, and NDUFS3 expression between the two groups of mice. The levels of 8-OHdG in the liver were markedly higher in 12-month-old SAMP10 mice than those in 3-month-old SAMP10 and SAMR1 mice. These results suggest that an increase in number of mitochondria or a collapse in the balance between the levels of complexes I and III results in an increase in the amount of ROS and induces the expression of antioxidant enzymes in the liver of SAMP10 mice at 3 months of age. Although young SAMP10 mice produce a large amount of ROS, they also produce suitable levels of antioxidant enzymes that decompose ROS; consequently accelerated aging does not occur in young SAMP10 mice. In addition to excessive ROS production which is an important cause of aging, the level of catalase was significantly lower in SAMP10 than that in SAMR1 mice. These results suggested that overexpression of ROS and a decrease in the levels of catalase resulted in the accelerated aging observed in older SAMP10 mice. Moreover, the level of phosphorylated FoxO-1a was increased in SAMP10 compared to that in SAMR1 mice though the total amount of FoxO-1a was not significantly different between the two groups in old age. These results suggest that some impairment in the regulation mechanism of FoxO-1a phosphorylation is responsible for abnormal catalase expression and that a significant decrease in the level of catalase with aging decisively affects the metabolic balance of ROS; thus, ROS that cannot be metabolized contributes to the accelerated aging of SAMP10 mice.