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1.
Sci Rep ; 11(1): 20159, 2021 10 11.
Article in English | MEDLINE | ID: mdl-34635711

ABSTRACT

Paraquat (PQ) is a widely used fast-acting pyridine herbicide. Accidental ingestion or self-administration via various routes can cause severe organ damage. Currently, no effective antidote is available commercially, and the mortality rate of poisoned patients is exceptionally high. Here, the efficacy of anthrahydroquinone-2-6-disulfonate (AH2QDS) was observed in treating PQ poisoning by constructing in vivo and ex vivo models. We then explored the detoxification mechanism of AH2QDS. We demonstrated that, in a rat model, the PQ concentration in the PQ + AH2QDS group significantly decreased compared to the PQ only group. Additionally, AH2QDS protected the mitochondria of rats and A549 cells and decreased oxidative stress damage, thus improving animal survival and cell viability. Finally, the differentially expressed genes were analysed in the PQ + AH2QDS group and the PQ group by NextGen sequencing, and we verified that Nrf2's expression in the PQ + AH2QDS group was significantly higher than that in the PQ group. Our work identified that AH2QDS can detoxify PQ by reducing PQ uptake and protecting mitochondria while enhancing the body's antioxidant activity.


Subject(s)
Anthraquinones/pharmacology , Antidotes/pharmacology , Antioxidants/pharmacology , Mitochondria/drug effects , Oxidative Stress , Paraquat/poisoning , Poisoning/prevention & control , A549 Cells , Animals , Cell Survival , Herbicides/poisoning , Humans , Male , Mitochondria/pathology , Poisoning/etiology , Poisoning/pathology , Rats , Rats, Sprague-Dawley
2.
Br J Nutr ; 121(11): 1279-1286, 2019 06.
Article in English | MEDLINE | ID: mdl-30837009

ABSTRACT

Maternal one-carbon metabolism during pregnancy is crucial for fetal development and programming by DNA methylation. However, evidence on one-carbon biomarkers other than folate is lacking. We, therefore, investigated whether maternal plasma methyl donors, that is, choline, betaine and methionine, are associated with birth outcomes. Blood samples were obtained from 115 women during gestation (median 26·3 weeks, 90 % range 22·7-33·0 weeks). Plasma choline, betaine, methionine and dimethylglycine were measured using HPLC-tandem MS. Multivariate linear and logistic regression models were used to estimate the association between plasma biomarkers and birth weight, birth length, the risk of small-for-gestational-age and large-for-gestational-age (LGA). Higher level of maternal betaine was associated with lower birth weight (-130·3 (95 % CI -244·8, -15·9) per 1 sd increment for log-transformed betaine). Higher maternal methionine was associated with lower risk of LGA, and adjusted OR, with 95 % CI for 1 sd increase in methionine concentration was 0·44 (95 % CI 0·21, 0·89). Stratified analyses according to infant sex or maternal plasma homocysteine status showed that reduction in birth weight in relation to maternal betaine was only limited to male infants or to who had higher maternal homocysteine status (≥5·1 µmol/l). Higher maternal betaine status was associated with reduced birth weight. Maternal methionine was inversely associated with LGA risk. These findings are needed to be replicated in future larger studies.


Subject(s)
Betaine/blood , Birth Weight , Maternal Nutritional Physiological Phenomena/physiology , Pregnancy Trimesters/blood , Adult , Choline/blood , Female , Homocysteine/blood , Humans , Infant, Newborn , Infant, Small for Gestational Age , Male , Methionine/blood , Pregnancy , Sarcosine/analogs & derivatives , Sarcosine/blood
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