Scatchard analysis of methane sulfinic acid production from dimethyl sulfoxide: A method to quantify hydroxyl radical formation in physiologic systems

Babbs, Charles F.; Griffin, David

doi:10.1016/0891-5849(89)90042-7

Cited by 82 publications

(41 citation statements)

References 54 publications

(40 reference statements)

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“…In this research we have been able to develop a simple and effective means to detect hydroxyl radicals in biologic systems by trapping them with dimethyl sulfoxide (DMSO) and measuring the primary, non-radical product of the trapping reaction, methane sulfinic acid (MSA) [32]. Searching for productive applications of this new method, we tested without success the ability of colon bacteria, obtained from feces, to stimulate free radical production in rat lung when the bacteria were injected into the pulmonary circulation.…”

Section: Evolution Of the Hypothesis And Relevant Physiological Mechamentioning

confidence: 99%

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Free radicals and the etiology of colon cancer

Babbs

1990

Free Radical Biology and Medicine

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313

174

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This hypothesis paper reviews diverse evidence suggesting that intracolonic production of oxygen radicals may play a role in carcinogenesis. The hypothesis began to evolve when the author made the chance discovery that 1/10,000 dilutions of feces generated detectable quantities of highly reactive hydroxyl radicals (HO). The rate of HO formation, detected using DMSO as a molecular probe, was quite remarkable, corresponding to that which would be produced by over 10,000 rads of gamma irradiation per day, absorbed in the periphery of the fecal mass adjacent to the mucosa. The relatively high concentrations of iron in feces, together with the ability of bile pigments to act as iron chelators that support Fenton chemistry, may very well permit efficient HO generation from superoxide and hydrogen peroxide produced by bacterial metabolism. Such free radical generation in feces could provide a missing link in our understanding of the etiology of colon cancer: the oxidation of procarcinogens either by fecal HO, or by secondary peroxyl radicals (ROO) to form active carcinogens or mitogenic tumor promotors. Intracolonic free radical formation may explain the high incidence of cancer in the colon and rectum, compared to other regions of the GI tract, as well as the observed correlations of a higher incidence of colon cancer with red meat in the diet, which increases stool iron, and with excessive fat in the diet, which may increase the fecal content of procarcinogens and bile pigments. OVERVIEW OF THE HYPOTHESIS AND RELEVANT CHEMICAL MECHANISMSMy intention in this hypothesis paper is to present a new hypothesis suggesting how oxygen derived free radicals, generated in fecal material next to colonic epithelium, may play a significant role in the etiology of colon cancer. This hypothesis derives from an earlier conjecture by Graf and Eaton [1], coupled with the serendipitous discovery in our laboratory that highly reactive HO radicals can be produced abundantly by suspensions of feces under aerobic conditions. As do many other hypotheses for the pathogenic effects of oxygen centered free radicals in biologic systems [2][3][4][5][6], this one also invokes the superoxide driven Fenton reaction:In feces a ready biologic source of superoxide is the respiratory activity of bacteria [7][8][9][10], notably E. coli [11], perhaps together with spontaneous autoxidation of ferrous iron chelates that have been previously reduced by metabolites of the anerobic subpopulation of fecal flora. Another intriguing source of colonic superoxide is the lipoxygenase activity of normal or sloughed colonic epithelial cells [12]. The necessary iron is provided from the diet, since only a small fraction of dietary iron is absorbed in upper GI tract [13,14]. Hydroxyl (HO) radicals so formed within the colon could easily trigger a variety of carcinogenic mechanisms. For example, they could participate in aromatic hydroxylation reactions [15,16] to form carcinogenic products [17]; they could abstract hydrogen atoms from indoles to form radicals t...

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Section: Evolution Of the Hypothesis And Relevant Physiological Mechamentioning

confidence: 99%

“…1 to 1.0 M [32,52,53] to trap the major portion of HO radicals generated and thus estimate their true abundance. Fortunately, DMSO is an extremely nontoxic [54,55] and rapidly penetrating molecular probe that can be tolerated by living tissues in adequately high concentrations [54,[56][57][58][59][60].…”

Section: Preliminary Tests Of the Hypothesismentioning

confidence: 99%

Free radicals and the etiology of colon cancer

Babbs

1990

Free Radical Biology and Medicine

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313

174

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“…Because such large quantities of sulfasalazine are given (and required), the concentrations achieved approach those necessary for efficient scavenging of O H  [83]. In addition to acting as a phenolic antioxidant, there is also the intriguing possibility that 5-ASA may also function as an iron chelator that inhibits Fenton chemistry.…”

Section: Effectiveness Of Azulfadine (Sulfasalazine) Which May Act Amentioning

confidence: 99%

Oxygen radicals in ulcerative colitis

Babbs

1992

Free Radical Biology and Medicine

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268

169

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This article reviews the pathophysiologic concept that superoxide and hydrogen peroxide, generated by activated leukocytes, together with low-molecular-weight chelate iron derived from fecal sources and from denatured hemoglobin, amplify the inflammatory response and subsequent mucosal damage in patients with active episodes of ulcerative colitis. The putative pathogenic mechanisms reviewed are as follows: ( l ) Dietary iron is concentrated in fecal material owing to normally limited iron absorption. (2) Mucosal bleeding, characteristic of ulcerative colitis, as well as supplemental oral iron therapy for chronic anemia, further conspire to maintain or elevate mucosal iron concentration in colitis. (3) Fenton chemistry, driven especially by leukocyte-generated superoxide and hydrogen peroxide, leads to formation of hydroxyl radicals. (4) The resultant oxidative stress leads to the extension and propagation of crypt abscesses, either through direct membrane disruption by lipid peroxidation or through generation of secondary toxic oxidants such as chloramines. (5) Chemotactic products of lipid peroxidation, including 4-hydroxynonenal, provide positive feedback to accelerate this inflammatory/oxidative process, leading to acute exacerbations of the disease. (6) Other oxidized products, such as oxidized tryptophan metabolites, created by free radical mechanisms in or near the mucosa, may act as carcinogens or tumor promotors that contribute to the exceedingly high incidence of colon carcinoma in patients suffering from chronic ulcerative colitis. In this way, self-sustaining cycles of oxidant formation may amplify flare-ups of inflammation and mucosal injury in ulcerative colitis. This concept, if proved correct by subsequent research, would provide a rationale for several novel clinical approaches to the management of ulcerative colitis, including use of SOD mimetics, iron chelators, and chain-breaking antioxidants.

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“…Thirdly, it is nontoxic at relatively high concentrations, which makes it suitable to determine • OH in some AOPs involving microorganism [18,19]. Fourthly, it is highly reactive with the hydroxyl radicals (k = 4.5 ∼ 7.1 × 10 9 mol L −1 s −1 ) forming methanesulfinic acid (MSA), methyl radicals and formaldehyde [20][21][22][23]:…”

Section: Introductionmentioning

confidence: 99%

Determination of hydroxyl radicals in advanced oxidation processes with dimethyl sulfoxide trapping and liquid chromatography

Tai

Peng

Liu

et al. 2004

Analytica Chimica Acta

244

109

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In this paper, a simple and sensitive method for the determination of hydroxyl radicals generated in advanced oxidation processes is described. The proposed method employed the reaction between hydroxyl radicals and dimethyl sulfoxide (DMSO) to generate quantitatively formaldehyde, which then reacted with 2,4-dinitrophenylhydrazine (DNPH) to form the corresponding hydrazone (HCHO-DNPH) and analyzed by liquid chromatography-UV. Factors affecting the derivatization reaction of HCHO and trapping reaction of hydroxyl radicals, as well as the applicability of the method, were investigated. The detection limit for hydroxyl radicals was 0.54 mol L −1 . The method had been used to determine the yield of hydroxyl radicals in various advanced oxidation processes (AOPs) to compare their oxidation ability.

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Scatchard analysis of methane sulfinic acid production from dimethyl sulfoxide: A method to quantify hydroxyl radical formation in physiologic systems

Cited by 82 publications

References 54 publications

Free radicals and the etiology of colon cancer

Free radicals and the etiology of colon cancer

Oxygen radicals in ulcerative colitis

Determination of hydroxyl radicals in advanced oxidation processes with dimethyl sulfoxide trapping and liquid chromatography

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