Effect of glucose-cysteine adduct as a cysteine prodrug in rats

Abstract

Summary. Effect of intraperitoneal administration (5mmol/kg of body weight) of glucose-cysteine adduct (glc-cys) as a cysteine prodrug in rat tissues was studied. Cysteine levels in liver and kidney increased to 1.08 and 1.98~mol per g or ml, respectively, at 2h after the administration. GSH levels did not change substantially. However, when glc-cys was injected to rats treated with diethyl maleate, a GSH-depleting agent, the decreased GSH levels were restored rapidly. The recoveries in liver and kidney were 72% at lh and 66% at 2h, respectively, after glc-cys administration. Metabolism of glc-cys was assessed by urinary excretion of glc-cys, sulfate and taurine. Average excretion of glc-cys was 2.86mmol/kg/24h after glc-cys administration. Increased excretions of sulfate and taurine were 0.77 and 0.14 mmol/kg/24 h, respectively. Data show that, although glc-cys excretion was relatively rapid, glc-cys was effectively utilized for GSH synthesis in GSH-depleted tissues.

Cysteine Donor-Based Brain-Targeting Prodrug: Opportunities and Challenges

“…Up to now, several Cys donors, including glucose-cysteine [ 81 ], L -ribose-cysteine [ 82 ], 2- N -propylthiazolidine-4-carboxylic acid [ 83 ], N -acetylcysteine [ 84 ], 2-methylthiazolidine-4-carboxylic acid, 2- N -propylthiazolidine-4-carboxylic acid [ 85 ], S , N -diacetylcysteine monoethyl ester [ 86 ], L -2-oxothiazolidine-4-carboxylic acid [ 87 ], and 2-methyl-thiazolidine-2, 4-dicarboxylic acid [ 88 ], have been reported and developed. Among them, N -acetylcysteine (NAC) and L -2-oxothiazolidine-4-carboxylic acid (OTC) are the Cys donors that received extensive investigations and applications ( Figure 5 ).…”