Ulcer Formation in Rat Stomach with Diethyldithiocarbamate

Oginö, Kazuhíde; Oka, Shinji; Matsuura, Shinjiro; Sakaida, Isao; Yoshimura, Sayaka; Matsuda, Kazuya; Sasaki, Yoshiyuki; Yamamoto, K.; Yoshikawa, Toshikazu; Okazaki, Yukinori; Takemoto, Tadayoshi

doi:10.3164/jcbn.3.189

Cited by 22 publications

(8 citation statements)

References 19 publications

(18 reference statements)

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“…5) . DDC is a powerful copper-chelating agent, an inhibitor of SOD, and a scavenger of O 2 d) (Ogino et al 1987). The decrease in DCF fluorescence after addition of DDC (Fig.…”

Section: C9 and C10 Hydrocarbon Solvents Elevate Respiratory Burst Inmentioning

confidence: 95%

Transcellular signalling pathways and TNF-? release involved in formation of reactive oxygen species in rat alveolar macrophages exposed to tert-butylcyclohexane

Aam

Myhre

Fonnum

2003

Archives of Toxicology

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In the present work, the effects of aliphatic ( n-nonane and n-decane), alicyclic (1,2,4-trimethylcyclohexane and tert-butylcyclohexane, t-BCH) and aromatic (trimethylbenzene and tert-butylbenzene) hydrocarbon solvents on formation of reactive oxygen species (ROS) and the proinflammatory cytokine TNF-alpha in rat alveolar macrophages (AM) have been investigated. Formation of ROS was assessed by monitoring oxidation of 2',7'-dichlorofluorescin to 2',7'-dichlorofluorescein (DCF), and the proinflammatory cytokine tumour necrosis factor alpha (TNF-alpha) was detected using an enzyme-linked immunosorbent assay. DCF fluorescence was elevated in a concentration-dependent manner by the alicyclic hydrocarbons. The involvement of transcellular signalling pathways in the production of ROS by t-BCH, the most active compound, was elucidated by use of specific inhibitors. Preincubation of the AM with the mitogen-activated protein kinase (ERK 1/2) inhibitor U0126, the protein kinase C inhibitor bisindolylmaleimide, the superoxide dismutase inhibitor diethyldithiocarbamate, and the iron ion chelating agent deferoxamine reduced the DCF fluorescence significantly. t-BCH gave an increase in TNF-alpha release. Further, nitric oxide production measured by a modified Griess method, and intracellular calcium concentration measured by fura-2, were increased in the rat AM after exposure to t-BCH.

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“…5) . DDC is a powerful copper-chelating agent, an inhibitor of SOD, and a scavenger of O 2 d) (Ogino et al 1987). The decrease in DCF fluorescence after addition of DDC (Fig.…”

Section: C9 and C10 Hydrocarbon Solvents Elevate Respiratory Burst Inmentioning

confidence: 95%

Transcellular signalling pathways and TNF-? release involved in formation of reactive oxygen species in rat alveolar macrophages exposed to tert-butylcyclohexane

Aam

Myhre

Fonnum

2003

Archives of Toxicology

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“…Salim [36] found that radical removing agents such as dimethylsulfoxide and allopurinol, prevented the de velopment of chronic duodenal ulcers produced by intra venous reserpine. Ogino et al [37] reported that diethyldithiocarbamate, an inhibitor of CuZnSOD, was ulceragenic and that reactive oxygen species were involved in the pathogenesis of mucosal injury. It has, however, been an unsolved problem whether reactive oxygen species can cause gastric deep ulcer.…”

Section: Discussionmentioning

confidence: 99%

A New Gastric Ulcer Model in Rats Produced by Ferrous Iron and Ascorbic Acid Injection

Naito¹,

Yoshikawa²,

Yoneta³

et al. 1995

Digestion

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We developed a new gastric ulcer model in which the ulcers are induced by the local injection of a ferrous iron and ascorbic acid (Fe/ASA) solution into the gastric wall. These ulcers resemble human gastric ulcers that penetrate the muscularis mucosa. The involvement of oxygen radical-mediated lipid peroxidation as the cause of these ulcers was investigated. With ferrous iron or ascorbic acid alone, gastric ulcers did not form, whereas penetrating ulcers were produced by the simultaneous injection of the Fe/ASA solution in a dose-dependent manner. Lipid peroxides significantly accumulated in the gastric mucosa from 1 to 24 h after the injection of the Fe/ASA solution. This increase in lipid peroxides preceded grossly evident gastric ulcer. Treatment with superoxide dismutase (SOD, recombinant human CuZnSOD) significantly reduced the size of the ulcers and inhibited the accumulation in lipid peroxides in the gastric mucosa, while treatment with apo-SOD or heat-inactivated SOD did not. These results suggest that lipid peroxidation mediated by oxygen radicals plays a crucial role in the pathogenesis of the gastric ulceration induced by the Fe/ASA solution.

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“…It is well known that DDC has many biological actions. With regard to the toxic effect of DDC, it has been reported to potentiate oxygen toxicity in brain (Puglia & Loeb 1984) and lung (Goldstein et al 1979).and to cause gastric ulcers (Ogino et al 1987;Ishiyama et al 1988). It has been suggested that these deleterious effects of DDC were due to an inhibition of cytosolic SOD activity.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that DDC potentiates oxygen (Puglia & Loeb 1984) and xenobiotics toxicities (Goldstein et al 1979) and causes astrocyte cell toxicity (Trombetta et al 1988). We have reported previously that DDC caused gastric ulcers in rats (Ogino et al 1987;Ishiyama et al 1988). In the liver, it has been reported that long-term treatment with disulfiram, an oxidized form of DDC, caused hepatotoxicity in man (Keeffe & Smith 1974;Eisen & Ginsberg 1975;Ranek & Andeasen 1977) but there have been no such reports in experimental animals.…”

mentioning

confidence: 88%

Hepatotoxicity of Diethyldithiocarbamate in Rats

Ishiyama¹,

Oginö²,

Shimomura³

et al. 1990

Pharmacology & Toxicology

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Hepatotoxicity of diethyldithiocarbamate (DDC) was investigated in rats. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were markedly elevated 24 hr after subcutaneous administration of DDC and histologically, the liver showed submassive necrosis. A sustained inhibition in the liver of Cu,Zn-superoxide dismutase (Cu-SOD) activity was observed following DDC treatment. DDC produced a significant loss in liver reduced glutathione (GSH) level after 1 hr, but the nadir was observed later than that of Cu-SOD. Catalase activity decreased gradually from 7 hr. Thiobarbituric acid reactive substances (TBARS) in the liver were significantly increased from 15 hr. Hepatic haemodynamics were scarcely changed up to 15 hr. Desferrioxamine (a chelator of iron) and piperonyl butoxide (an inhibitor of cytochrome P-450) prevented DDC-induced increases of both ALT and TBARS, but GSH did not, DDC hepatotoxicity was not changed by phenobarbital induction. Thus, we have shown that subcutaneous dose of DDC caused hepatotoxicity in rats. Although the exact sequence of its hepatotoxic factors is unproven, it seems likely that lipid peroxidation through the dysfunction of antioxidant defence factors and a toxic metabolite contribute to the formation of this liver injury.

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Ulcer Formation in Rat Stomach with Diethyldithiocarbamate

Cited by 22 publications

References 19 publications

Transcellular signalling pathways and TNF-? release involved in formation of reactive oxygen species in rat alveolar macrophages exposed to tert-butylcyclohexane

Transcellular signalling pathways and TNF-? release involved in formation of reactive oxygen species in rat alveolar macrophages exposed to tert-butylcyclohexane

A New Gastric Ulcer Model in Rats Produced by Ferrous Iron and Ascorbic Acid Injection

Hepatotoxicity of Diethyldithiocarbamate in Rats

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