Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues: a specialized function of the colonic mucosa

doi:10.1016/S0006-2952(01)00657-8

Biochemical Pharmacology

Volume 62, Issue 2, 15 July 2001, Pages 255-259

https://doi.org/10.1016/S0006-2952(01)00657-8 Get rights and content

Abstract

Colonic bacteria release large quantities of the highly toxic thiols hydrogen sulfide (H₂S) and methanethiol (CH₃SH). These gases rapidly permeate the colonic mucosa, and tissue damage would be expected if the mucosa could not detoxify these compounds rapidly. We previously showed that rat cecal mucosa metabolizes these thiols via conversion to thiosulfate. The purpose of the present study in rats was to determine if this conversion of thiols to thiosulfate is (a) a generalized function of many tissues, or (b) a specialized function of the colonic mucosa. The tissues studied were mucosa from the cecum, right colon, mid-colon, ileum, and stomach; liver; muscle; erythrocytes; and plasma. The metabolic rate was determined by incubating homogenates of the various tissues with H₂³⁵S and CH₃³⁵SH and measuring the rate of incorporation of ³⁵S into thiosulfate and sulfate. The detoxification activity of H₂S (expressed as nmol/mg per min) that resulted in thiosulfate production was at least eight times greater for cecal and right colonic mucosa than for the non-colonic tissues. Thiosulfate production from CH₃SH was at least five times more rapid for cecal and right colonic mucosa than for the non-colonic tissues. We conclude that colonic mucosa possesses a specialized detoxification system that allows this tissue to rapidly metabolize H₂S and CH₃SH to thiosulfate. Presumably, this highly developed system protects the colon from what otherwise might be injurious concentrations of H₂S and CH₃SH. Defects in this detoxification pathway possibly could play a role in the pathogenesis of various forms of colitis.

Introduction

Colonic bacteria produce large quantities of the highly toxic gases hydrogen sulfide (H₂S) and methanethiol (CH₃SH) [1]. Since the intestine is extremely permeable to H₂S and CH₃SH [1], severe tissue damage would be expected if the colonic mucosa did not possess an efficient means for detoxifying these gases.

High molecular weight thiols are detoxified via a methylation reaction catalyzed by thiol S-methyltransferase [2], [3], and it has been commonly assumed that the colonic mucosa utilizes a similar mechanism to detoxify the low molecular weight thiols H₂S and CH₃SH [4], [5]. However, we recently found that the cecal mucosa of the rat disposed of these compounds primarily via oxidation to thiosulfate [6]. The goal of the present study, carried out with rat tissues, was to determine if this ability to convert H₂S and CH₃SH to thiosulfate is (a) a specialized function of the cecal mucosa, or (b) a detoxification mechanism common to a variety of tissues.

Section snippets

Tissues

Under pentobarbital anesthesia, tissue was obtained from five male Sprague–Dawley rats weighing 300–400 g. Tissues studied included mucosa obtained from the cecum, right colon, mid-colon, ileum, and stomach, as well as the liver, abdominal wall muscle, erythrocytes, and plasma. The gut segments were first rinsed with isotonic saline to remove all luminal debris, and then the mucosa was scraped off using the edge of a glass microscope slide. All tissue samples were maintained on ice until

Results

The rates of production of thiosulfate and sulfate during incubation of tissues with H₂S are shown in Table 1. Cecal and right colonic mucosa oxidized H₂S to thiosulfate at least eight times more rapidly than did any other non-colonic tissue, whereas the rate of production of sulfate was roughly equal for the various tissues. The total oxidation rate of H₂S (thiosulfate plus sulfate production) was at least four times faster for right colonic mucosa than for any of the other tissues tested.

Discussion

The low molecular weight thiols, H₂S and CH₃SH, have ld₅₀ values for rodents that are on the order of those for cyanide [7]. The acute toxicity of these compounds is thought to result from their ability to inhibit cytochrome oxidase via binding to the ferric moiety of cytochrome aa₃[8]. In addition, H₂S also appears to cause damage via mechanisms that are independent of cytochrome oxidase inhibition, such as hyperpolarization of potassium channels and alterations of neurotransmitters [9].

While

Acknowledgements

This work was supported, in part, by the Department of Veterans Affairs and The National Institute of Diabetes and Digestive and Kidney Disease, Grant R01 DK 13309–25.

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Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues: a specialized function of the colonic mucosa

Abstract

Introduction

Section snippets

Tissues

Results

Discussion

Acknowledgements

Biochim Biophys Acta

Biochem Pharmacol

Biochim Biophys Acta

Am J Gastroenterol

Gastroenterology

Lancet

Gastroenterology

Production and elimination of sulfur-containing gases in the rat colon

Am J Physiol

S-Methylation of d- and l-penicillamine by human erythrocyte membrane thiol methyltransferase

Drug Metab Dispos

Sulfur metabolism in ulcerative colitisinvestigation of detoxification enzymes in peripheral blood

Dig Dis Sci