ascorbic-acid and perfluorooctanoic-acid

There is limited evidence whether environmental exposure to perfluorinated compounds (PFCs) affects insulin resistance (IR) and whether vitamin C intake protects against the adverse effect of PFCs. This study was carried out to investigate the effect of PFCs on IR through oxidative stress, and the effects of a 4-week consumption of vitamin C supplement compared placebo on development of IR by PFCs.. For a double-blind, community-based, randomized, placebo-controlled crossover intervention of vitamin C, we assigned 141 elderly subjects to both vitamin C and placebo treatments for 4 weeks. We measured serum levels of PFCs to estimate PFC exposures and urinary levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) for oxidative stress. We also measured levels of fasting glucose and insulin and derived the homeostatic model assessment (HOMA) index to assess IR.. Perfluorooctane sulfonate (PFOS) and perfluorododecanoic acid (PFDoDA) levels were found to be positively associated with HOMA index at the baseline and after placebo treatment. Risks of IR for the top decile of PFOS and PFDoDA exposures were significantly elevated compared with those with lower PFOS and PFDoDA exposures (both, P < 0.0001). However, the effects of PFOS and PFDoDA on HOMA disappeared after vitamin C supplementation (both, P > 0.30). Furthermore, PFOS and PFDoDA levels were also significantly associated with MDA and 8-OHdG levels, and MDA levels were positively associated with HOMA index.. PFOS and PFDoDA exposures were positively associated with IR and oxidative stress, and vitamin C supplementation protected against the adverse effects of PFOS and PFDoDA on IR.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aged, 80 and over; Ascorbic Acid; Asian People; Biomarkers; Blood Glucose; Caprylates; Cotinine; Creatinine; Cross-Over Studies; Deoxyguanosine; Dietary Supplements; Double-Blind Method; Fluorocarbons; Humans; Insulin; Insulin Resistance; Malondialdehyde; Middle Aged; Oxidative Stress; Republic of Korea

Perfluorooctanoic acid (PFOA) is widely used in industrial and consumer products of our daily life. It is well-documented that PFOA is closely associated with fatty liver disease. Recently, cumulating studies demonstrated the immunotoxicity of PFOA, but its harmful effect on the largest immune organ, spleen is still largely unknown. In the present study, we used PFOA-exposed mouse model together with comparative transcriptomic analysis to understand the molecular mechanisms underlying the immunotoxicity of PFOA. Furthermore, we investigated the possible use of vitamin C to reverse the PFOA-induced immunotoxicity in spleen. Our result showed that the PFOA exposure could reduce the spleen weight and plasma lymphocytes, and the splenic comparative transcriptomic analysis highlighted the alteration of cell proliferation, metabolism and immune response through the regulation of gene clusters including nicotinamide nucleotide transhydrogenases (NNT) and lymphocyte antigen 6 family member D and K (LY6D and LY6K). More importantly, the supplementation of vitamin C would relieve the PFOA-reduced spleen index and white blood cells. The bioinformatic analysis of transcriptome suggested its involvement in the spleen cell proliferation and immune response. For the first time, our study delineated the molecular mechanisms underlying the PFOA-induced immunotoxicity in the spleen. Furthermore, our results suggested that the supplementation of vitamin C had beneficial effect on the PFOA-altered spleen functions.

Topics: Animals; Ascorbic Acid; Caprylates; Fluorocarbons; Mice; Spleen

Perfluorooctanoic acid (PFOA) is a compound used as an industrial surfactant in chemical processes worldwide. Population and cross-sectional studies have demonstrated positive correlations between PFOA levels and human health problems.. Many studies have focused on the hepatotoxicity and liver problems caused by PFOA, with little attention to remediation of these problems. As an antioxidant, vitamin C is frequently utilized as a supplement for hepatic detoxification.. In this study, we use a mouse model to study the possible role of vitamin C in reducing PFOA-induced liver damage. Based on comparative transcriptomic and metabolomic analysis, we elucidate the mechanisms underlying the protective effect of vitamin C.. Our results show that vitamin C supplementation reduces signs of PFOA-induced liver damage including total cholesterol and triglyceride levels increase, liver damage markers aspartate, transaminase, and alanine aminotransferase elevation, and liver enlargement. Further, we show that the protective role of vitamin C is associated with signaling networks control, suppressing linoleic acid metabolism, reducing thiodiglycolic acid, and elevating glutathione in the liver.. The findings in this study demonstrate, for the first time, the utility of vitamin C for preventing PFOA-induced hepatotoxicity.

Topics: Animals; Ascorbic Acid; Caprylates; Cross-Sectional Studies; Fluorocarbons; Mice