期刊
ANTIOXIDANTS
卷 11, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/antiox11030483
关键词
chronic kidney disease; cysteine; hypertension; developmental origins of health and disease (DOHaD); renin-angiotensin system; gut microbiota; hydrogen sulfide; indole
资金
- Chang Gung Memorial Hospital, Kaohsiung, Taiwan and Cheng Shiu University, Kaohsiung, Taiwan [CORPG8L0261]
This study found that supplementing l- or d-cysteine during pregnancy can prevent offspring hypertension caused by maternal chronic kidney disease (CKD). The protective effects are related to reducing oxidative stress, modulating the renin-angiotensin system (RAS), and reshaping the gut microbiome.
Maternal chronic kidney disease (CKD) is linked to offspring hypertension. The gut microbiome and its tryptophan metabolites, nitric oxide (NO), and renin-angiotensin system (RAS) are closely related to the development of hypertension. Hydrogen sulfide (H2S) has shown an anti-hypertensive effect. Our objective was to test whether l- or d-cysteine supplementation in pregnancy can prevent hypertension programmed by maternal CKD in adult offspring and to explore the protective mechanisms. CKD was induced in pregnant Sprague Dawley rats by a 0.5% adenine diet for 3 weeks. l- or d-cysteine was supplemented at 8 mmol/kg body weight/day during pregnancy. Male offspring were sacrificed at the age of 12 weeks (n = 8 per group). Maternal CKD-induced hypertension was similarly prevented by l- or d-cysteine supplementation. The protective effects of l- and d-cysteine are related to reducing oxidative stress, rebalancing the RAS, and reshaping the gut microbiome. l-cysteine therapy protected adult offspring against hypertension and was associated with enhanced H2S production, restoration of NO bioavailability, enhancement of beneficial genera Oscillibacter and Butyricicoccus, depletion of indole-producing genera Alistipes and Akkermansia, and the reduction of several indole metabolites. d-cysteine treatment increased kynurenic acid, 3-hydroxykynurenine, and xanthurenic acid in the kynurenine pathway, decreased 5-hydroxytryptophan and serotonin in the serotonin pathway, and enriched genera Bacteroides and Odoribacter abundance. In summary, these results suggest that l- and d-cysteine protect against maternal CKD-induced offspring hypertension, likely by enhancing H2S production, modulating gut microbiota and its derived metabolites, and the restoration of NO and RAS.
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