Efficacy of l-cysteine in increasing circulatory hydrogen sulfide, nitrite, and 25-hydroxyvitamin D levels in Zucker diabetic fatty rats and in vitro treatment of hydrogen sulfide and nitrite in upregulating vitamin D hydroxylase genes in monocytes

Abstract

ABSTRACT: Dairy products, such as whey proteins, have been effectively used to enhance the effectiveness of vitamin D (VD) fortification and optimize circulating 25-hydroxyvitamin D [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 fatty (ZDF) rats were used as a model in this study to examine the hypothesis that LC supplementation enhances blood levels of H2S and nitrite (NO2) and reduces inflammation biomarkers. Rats were gavaged daily (orally) with either saline placebo or LC along with a high-calorie diet starting at 6 wk 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 BW gain in ZDF rats. Furthermore, to assess the effect 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 LC supplementation.

Keywords

• l-cysteine
• whey protein
• vitamin D
• hydrogen sulfide
• nitrite