Methionine derivatives diminish sulphide damage to colonocytes--implications for ulcerative colitis.

Roediger, W. E. W.; Babidge, Wendy; Millard, Susan

doi:10.1136/gut.39.1.77

Cited by 28 publications

(13 citation statements)

References 35 publications

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“…Evidence to support this role comes from studies on the capacity of SAMe to diminish ischemia/reperfusion injuries in clinical trials during liver transplantation [33]. Ulcerative colitis is also associated with a selective reduction of n-butyrate oxidation by the colonic epithelial cells [31]. The reasons for this action are not completely understood.…”

Section: Discussionmentioning

confidence: 97%

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Antioxidants as novel therapy in a murine model of colitis

Chen

McClain

et al. 2005

The Journal of Nutritional Biochemistry

203

147

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Section: Discussionmentioning

confidence: 97%

“…Bacterial production of anionic sulfide is reported to be increased in the colon of ulcerative colitis patients, and these sulfides can cause metabolic damage to colonocytes [31]. Sulfide toxicity in isolated colonocytes can be reversed by methyl donors.…”

Section: Discussionmentioning

confidence: 98%

Antioxidants as novel therapy in a murine model of colitis

Chen

McClain

et al. 2005

The Journal of Nutritional Biochemistry

203

147

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“…They are the most important source of oxidative energy for colonic mucosa and are predominantly produced in the colon by anaerobic bacterial fermentation of non-absorbed carbohydrates [3,23]. They also stimulate proliferation and promote cellular differentiation.…”

Section: Rectal Scfamentioning

confidence: 99%

Sodium butyrate enemas in the treatment of acute radiation-induced proctitis in patients with prostate cancer and the impact on late proctitis

Hille¹,

Herrmann²,

Kertesz³

et al. 2008

Strahlenther Onkol

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Purpose:To evaluate prospectively the effect of sodium butyrate enemas on the treatment of acute and the potential influence on late radiation-induced proctitis. Patients and Methods: 31 patients had been treated with sodium butyrate enemas for radiation-induced acute grade II proctitis which had developed after 40 Gy in median. During irradiation the toxicity was evaluated weekly by the Common Toxicity Criteria (CTC) and subsequently yearly by the RTOG (Radiation Therapy Oncology Group) and LENT-SOMA scale. Results: 23 of 31 patients (74%) experienced a decrease of CTC grade within 8 days on median. A statistical significant difference between the incidence and the severity of proctitis before start of treatment with sodium butyrate enemas compared to 14 days later and compared to the end of irradiation treatment course, respectively, was found. The median follow-up was 50 months. Twenty patients were recorded as suffering from no late proctitis symptom. Eleven patients suffered from grade I and 2 of these patients from grade II toxicity, too. No correlation was seen between the efficacy of butyrate enemas on acute proctitis and prevention or development of late toxicity, respectively. Conclusion: Sodium butyrate enemas are effective in the treatment of acute radiation-induced proctitis in patients with prostate cancer but have no impact on the incidence and severity of late proctitis. Natriumbutyrat-Einläufe in der Behandlung der akuten radiotherapieinduzierten Proktitis bei Patienten mit Prostatakarzinom und der Einfluss auf eine späte Proktitis. Eine prospektive UntersuchungZiel: Diese prospektive Untersuchung wurde durchgeführt, um den Effekt von Natriumbutyrat-Einläufen in der Therapie der akuten Proktitis sowie den potentiellen Einfluss auf radiogene rektale Spätreaktionen zu evaluieren. Patienten und Methodik: 31 Patienten wurden mit Natriumbutyrat-Einläufen bei radiogen induzierter akuter Grad-II-Proktitis behandelt, die im Mittel nach 40 Gy aufgetreten war. Während der Radiotherapie wurde die Toxizität wöchentlich anhand der Common Toxicity Criteria (CTC) und anschließend jährlich anhand der RTOG-und LENT-SOMA-Skalen erhoben. Ergebnisse: 23 von 31 Patienten (74%) erfuhren eine Abnahme des CTC-Grades innerhalb von 8 Tagen im Median. Dadurch war der Unterschied in der Häufigkeit und Schwere der Proktitis vor Therapiebeginn und 14 Tage später bzw. am Ende der Radiotherapie statistisch signifikant. Der mediane Follow-up lag bei 50 Monaten. 20 Patienten entwickelten keine späte Proktitis. 11 Patienten entwickelten eine Grad-I-und 2 von diesen Patienten ebenfalls eine Grad-II-Toxizität. Es konnte keine signifikante Korrelation zwischen der Effektivität der Natriumbutyrat-Einläufe und Prävention bzw. Entwicklung einer späten Toxizität entdeckt werden. Schlussfolgerung: Natriumbutyrat-Einläufe sind effektiv in der Behandlung der akuten radiotherapieinduzierten Proktitis bei Patienten mit Prostatakarzinom, haben aber keinen Einfluss auf die Häufigkeit und Schwere der späten Proktitis.Schlüsselwörter: Prostatakar...

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“…Recent literature assumes that a similar mechanism is used in the detoxification of the lowmolecular-weight thiols H 2 S and CH 3 SH (5)(6)(7)(8). Such methylation would result in the conversion of H 2 S to CH 3 SH, and then CH 3 SH to dimethylsulfide (CH 3 SCH 3 ), a relatively nontoxic compound.…”

Section: Introductionmentioning

confidence: 99%

Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa

Levitt¹,

Furne²,

Springfield³

et al. 1999

J. Clin. Invest.

225

155

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The colonic bacteria produce large quantities of hydrogen sulfide (H 2 S) and methanethiol (CH 3 SH), highly toxic compounds with LD 50 's for rodents that are on the same order of magnitude as cyanide. Given the very high exposure of the colonic mucosa to H 2 S and CH 3 SH, local tissue damage would be expected if the mucosa did not possess an efficient detoxification mechanism. The possibility that sulfide might be injurious to colonic mucosa was first proposed by Roediger and Nance (1), who postulated that excess sulfide production could play an etiological role in ulcerative colitis.A variety of high-molecular-weight thiols are detoxified in a methylation reaction catalyzed by thiol S-methyltransferase (2-4). Recent literature assumes that a similar mechanism is used in the detoxification of the lowmolecular-weight thiols H 2 S and CH 3 SH (5-8). Such methylation would result in the conversion of H 2 S to CH 3 SH, and then CH 3 SH to dimethylsulfide (CH 3 SCH 3 ), a relatively nontoxic compound. However, the reported rate of methylation of H 2 S by rat colonic mucosa is only about 10 -13 mol/min per milligram of protein (8). This activity appears to be many orders of magnitude less than that required to metabolize H 2 S released in the colon, which we found to occur at a rate of about 10 -7 mol/min in the rat cecum (9).In the process of incubating H 2 S and CH 3 SH with rat cecal mucosa, we observed that both gases disappeared far more rapidly than could be accounted for by reported methylation rates. The present report describes in vitro and in vivo experiments demonstrating that the colonic mucosa possesses a very efficient, but largely unrecognized, system to metabolize H 2 S and CH 3 SH. This system proceeds, not by methylation, but rather by demethylation of CH 3 SH to H 2 S and oxidation of H 2 S primarily to thiosulfate. MethodsTissues. Cecal and hepatic tissues were obtained from male Sprague-Dawley rats (300-400 g) while the animals were under pentobarbital anesthesia. The cecum was first cleansed of luminal debris by rinsing with isotonic saline, and the mucosa was then scraped off using the edge of a glass microscope slide. Tissue samples were maintained on ice until homogenized in an ice-cold buffer solution in a ratio of 1 part tissue to 15 parts buffer (wt/vol). Homogenization was performed with a Duall grinder (Kontes, Vineland, New Jersey, USA) with a Teflon pestle, using 8-10 strokes. Except when noted, studies were carried out using RPMI buffer, which has a pH of 7.4 when equilibrated with 5% CO 2 . This buffer contains a variety of electrolytes, including 0.4 mM sulfate. In addition, some studies were carried out in 0.1 M PBS (pH 7.0) or a buffer system containing 1.15% KCl, 5 mM Tris-HCl (pH 7.8), and 0.475 mM of the methyl donor S-adenosylmethionine, a milieu used in previously published studies (7) designed to assess thiol S-methyltransferase activity.Incubation studies. A 32-µL volume of homogenate or buffer was added to 20-mL polypropylene syringes. (Preliminary studies showed that bo...

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Methionine derivatives diminish sulphide damage to colonocytes--implications for ulcerative colitis.

Cited by 28 publications

References 35 publications

Antioxidants as novel therapy in a murine model of colitis

Antioxidants as novel therapy in a murine model of colitis

Sodium butyrate enemas in the treatment of acute radiation-induced proctitis in patients with prostate cancer and the impact on late proctitis

Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa

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