Efficacy of L-cysteine in increasing circulatory hydrogen sulfide, nitrite, and 25(OH)VD levels in ZDF rats and in vitro treatment of H2S and NO2 in upregulating VD hydroxylase genes in monocytes

Abstract

Dairy products, such as whey proteins, have been effectively utilized to enhance the effectiveness of vitamin D fortification and optimize circulating 25(OH)VD levels. Whey protein is rich in L-cysteine (LC) which is the precursor of hydrogen sulfide (H2S), enhances glutathione (GSH) biosynthesis, and promotes positive nitrogen balance. Zucker diabetic rats (ZDF) were used as a model in this study, to examine the hypothesis that LC supplementation enhances blood levels of H2S and nitrite (NO2) while reducing inflammation biomarkers. Rats were gavaged daily (orally) with either saline placebo or L-cysteine along with a high-calorie diet starting at 6 weeks of age. Fasting blood levels showed LC supplementation significantly increased circulatory levels of H2S and NO2 compared with placebo rats. LC supplementation increased plasma concentration of 25(OH)VD and vitamin C and lowered leptin and body weight gain in ZDF rats. Furthermore, to assess the impact of H2S and NO2 in raising 25(OH)VD levels, the in vitro effect of H2S/NO2 on vitamin D metabolism genes was examined using THP-1 monocytes. The exogenous H2S and NO2 treatment upregulated the relative expression of CYP2R1 and CYP27B1 genes in cultured monocytes. This study suggests a potential mechanism for the observed increase in circulating 25(OH)VD levels following L-cysteine supplementation.