Gestational α-ketoglutarate supplementation ameliorates arsenic-induced hepatic lipid deposition via epigenetic reprogramming of ß-oxidation process in female offspring.

Inorganic trivalent arsenic (iAsⅢ) at environmentally relevant levels has been found to cause developmental toxicity. Maternal exposure to iAsⅢ leads to enduring hepatic lipid deposition in later adult life. However, the exact mechanism in iAsⅢ induced hepatic developmental hazards is still unclear. In this study, we initially found that gestational exposure to iAsⅢ at an environmentally relevant concentration disturbs lipid metabolism and reduces levels of alpha-ketoglutaric acid (α-KG), an important mitochondrial metabolite during the citric acid cycle, in fetal livers. Further, gestational supplementation of α-KG alleviated hepatic lipid deposition caused by early-life exposure to iAsⅢ. This beneficial effect was particularly pronounced in female offspring. α-KG partially restored the ß-oxidation process in hepatic tissues by hydroxymethylation modifications of carnitine palmitoyltransferase 1a (Cpt1a) gene during fetal development. Insufficient ß-oxidation capacities probably play a crucial role in hepatic lipid deposition in adulthood following in utero arsenite exposure, which can be efficiently counterbalanced by replenishing α-KG. These results suggest that gestational administration of α-KG can ameliorate hepatic lipid deposition caused by iAsⅢ in female adult offspring partially through epigenetic reprogramming of the ß-oxidation pathway. Furthermore, α-KG shows potential as an interventive target to mitigate the harmful effects of arsenic-induced hepatic developmental toxicity.

[Tissue distribution on methyl nonyl ketone of the volatile oil from Houttyunia cordata in mice].

OBJECTIVE: To study the tissue distribution on methyl nonyl ketone of the volatile oil from Houttuynia cordata in mice in order to provide a guidance for the clinical trial. METHODS: The concentrations of the volatile oil from Houttuynia cordata in biological samples were determined by GC method. RESULTS: After a single oral dose of 5.0 g/kg volatile oil from Houttuynia cordata in mice, parent drug was mainly distributed in windpipe, intesting, liver, kidney, heart, blood, spleen, lung, brain, muscle; after 7 hours, parent drug of every tissue decreased over 90%. CONCLUSION: Parent drug mianly distributes in windpipe, intestine, liver, kidney. The experiment provides pharmacokinetic evidence for the rational administration and the further development of Houttuynia cordata.