Effect of Oral Glutathione Monoethyl Ester and Glutathione on Circulating and Hepatic Sulfhydrils in the Rat

Abstract

Glutathione (GSH) plays an important role in the detoxification of reactive metabolites of oxygen and xenobiotics and as a source of cysteine. Since several clinical situations characterized by low circulating and intracellular GSH have been identified, there is a growing interest in pharmacological interventions to correct a deranged sulfhydril status. Therefore, the systemic bioavailability of orally administered GSH and glutathione monoethyl ester (GSHE) was examined in the rat. Following the intraduodenal administration of 0.5 mmol/kg of GSH and GSHE there was no significant increase in the concentrations of cysteine and GSH in plasma, but hepatic cysteine and GSH increased significantly, albeit transiently. Five mmol/kg of GSH and GSHE significantly increased circulating and hepatic cysteine and GSH. Following the administration of 0.5 and 5 mmol/kg of GSHE low concentrations of the ester were found in plasma and the liver, indicating that GSHE is not readily absorbed from the gastrointestinal tract, although it is not a substrate for gamma-glutamyl-transferase. GSHE resulted in a delayed release of cysteine and GSH compared to GSH, such that the concentrations of GSH and cysteine in liver and plasma were significantly higher 2 h after administration of GSHE than after GSH. The data indicate that the bioavailability of GSH and GSHE is low in the rat. Orally administered GSH and GSHE do not affect the circulating concentrations of GSH and cysteine unless very high doses are administered, but increase hepatic cysteine and GSH at lower doses because of the efficient extraction by the liver of cysteine originating from the breakdown of GSH and GSHE in the gut.

Long-term ingestion of reduced glutathione suppressed an accelerating effect of beef tallow diet on colon carcinogenesis in rats

“…In our previous study, supplementation with GSH restored the mucosal GSH/GSSG ratio and abrogated the peroxide-induced suppression of intestinal cell turnover [45]. Another study has indicated that supplementation with low-dose GSH increases hepatic cysteine, the precursor of GSH [46]. Consequently, the results of the present and previous studies indicate that oral chronic administration of GSH might have some antioxidant and anti-carcinogenic properties in rats fed with beef tallow after AOM pretreatment.…”

Protective effect of N-acetylcysteine on kidney as a remote organ after skeletal muscle ischemia-reperfusion

“…It has long been approved for the prevention of hepatic and renal damage following acetaminophen overdose 22 . This well documented effect traditionally has been attributed to the restoration of intracellular glutathione levels 23,24 , required for detoxification of an acetaminophen-derived toxic metabolite. N-acetylcysteine also may attenuate the course of hepatorenal syndrome, a renal vasoconstrictive response of indeterminate nature that develops during advanced liver failure.…”

Glutathione synthetase deficiency

“…sulphonamides and phenobarbitals, should be avoided. Administration of several cysteine delivery compounds, such as NAC, 2-oxothiazolidine-4-carboxylate (OTC; a 5-oxoproline analogue), methionine and S,N-diacetylcysteine monoethyl ester, increase the intracellular levels of GSH [61,62]. However, these compounds would generally be of limited value in raising GSH levels in GSS-deficient patients, as these patients are unable to form the tripeptide.…”