Gastric Mucosal Protection and Superoxide Dismutase

Oginö, Kazuhíde; Oka, Shinji; Okazaki, Yukinori; Takemoto, Tadayoshi

doi:10.1097/00004836-198812001-00019

Cited by 25 publications

(17 citation statements)

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“…8, 20] reported that indometha cin itself activated neutrophils, enhanced neutrophilendothelium adhesion interaction, and caused tissue damage through oxyradical formation. Since DDC is an inhibitor of the radical scavenging enzyme SOD, and since SOD has a negative influence on neutrophil activa tion [11,21], it is supposed that DDC might potentiate the cellular toxicity of indomethacin and worsens gastric lesions by accumulating superoxide radicals.…”

Section: Discussionmentioning

confidence: 99%

“…a potent metal chela tor, is known to inhibit copper-modulated cytosolic super oxide dismutase (SOD), which scavenges Superoxide radi cals and inhibits neutrophil activation [11][12][13]. If neutro phil-related oxyradical formation is primarily involved in the pathogenic events of indomethacin-induced injury, it may be assumed that DDC potentiates the cellular toxici ty of indomethacin and worsens gastric lesions by accu mulating superoxide radicals.…”

Section: Introductionmentioning

confidence: 99%

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Diethyldithiocarbamate, a Superoxide Dismutase Inhibitor, Reduces Indomethacin-lnduced Gastric Lesions in Rats

Takeuchi¹,

Takehara²,

Ohuchi

1996

Digestion

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We examined the effect of diethyldithiocarbamate (DDC), the superoxide dismutase (SOD) inhibitor, on the development of gastric lesions induced by indomethacin in rats. Indomethacin (25 mg/kg) was given subcutaneously, and gastric acid secretion, motility, lipid peroxidation, vascular permeability, and myeloperoxidase as well as gastric lesions were measured. Indomethacin produced high-amplitude contractions of the stomach and caused hemorrhagic lesions in the corpus mucosa with significant increase in neutrophil-related processes such as myeloperoxidase activity, vascular permeability and lipid peroxidation. These changes caused by indomethacin were all significantly inhibited by prior administration of atropine (3 mg/kg s.c). Pretreatment of the animals with DDC (75-1,000 mg/kg s.c.) prevented these lesions induced by indomethacin in the corpus mucosa in a dose-dependent manner ( > 100 mg/kg), though at high doses ( > 750 mg/kg) some damage was found in both the antrum and duodenum. DDC showed a significant inhibition against the gastric mucosal SOD activity ( > 400 mg/kg), yet potently suppressed the increase of lipid peroxidation, vascular permeability, and myeloperoxidase activity caused by indomethacin. DDC dose-dependently ( > 75 mg/kg) inhibited the enhancement of gastric motility caused by indomethacin and showed a weak antisecretory effect at high doses ( > 750 mg/kg). These results showed that DDC reduced indomethacin-induced gastric lesions by suppressing gastric motility, despite inhibiting SOD activity. This study also indicates the prime importance of gastric hypercontraction in the pathogenesis of this lesion model and suggests that other events including the neutrophil-related processes may be secondary to gastric hypercontraction caused by indomethacin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diethyldithiocarbamate, a Superoxide Dismutase Inhibitor, Reduces Indomethacin-lnduced Gastric Lesions in Rats

Takeuchi¹,

Takehara²,

Ohuchi

1996

Digestion

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“…In some cases, we examined the effects of allopurinol (50 mg/kg), glu tathione (200 mg/kg), SOD (50000 units/kg), cimetidine (100 mg/kg) and 16,16-dimethyl prostaglandin E2 (dmPGE2: 10 ,ug/kg) on the severity of the duodenal ulcers induced by DDC. The doses of these agents were selected to represent the inhibition of xanthine oxidase (9), radical scavenging activity (2,10), inhibi tion of acid secretion (5) or stimulation of duodenal alkaline secretion (11); and they were given s.c. 10 min before each injection of DDC.…”

Section: Methodsmentioning

confidence: 99%

“…Diethyldithiocarbamate (DDC), a potent metal chelator, is known to induce damage in the gastrointestinal mucosa in rats (1,2). Re cently, we found that repeated administration of DDC to fed rats produced penetrating ulcers in the duodenum with a high incidence (3).…”

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confidence: 92%

Duodenal Ulcers Induced by Diethyldithiocarbamate, a Superoxide Dismutase Inhibitor, in the Rat: Role of Antioxidative System in the Pathogenesis.

et al. 1991

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ABSTRACT-Pathogenesis of duodenal ulcers induced by diethyldithiocarbamate (DDC), a superoxide dismutase (SOD) inhibitor, was investigated in the rat. Repeat ed s.c. administration of DDC (750 mg/kg) every 12 hr induced duodenal ulcers in the fed rats, and the severity of the ulcers reached the maximum after three injections. DDC not only reduced basal acid output but also impaired duodenal alkaline secre tion. These ulcers were significantly prevented by antioxidative agents such as SOD (50000 units/kg, s.c.), allopurinol (50 mg/kg, s.c.) or glutathione (200 mg/kg, s.c.) as well as the antisecretory agent cimetidine (100 mg/kg, s.c.). The impaired HCO3 re sponse caused by DDC was partially but significantly reversed by either SOD (15000 units/kg/hr, i.v.), allopurinol or glutathione; and SOD by itself significantly elevated the rate of basal alkaline secretion. 16,16-Dimethyl prostaglandin E2 (10 ,ug/kg, s.c.) increased duodenal HCO3 output in the presence of DDC and significantly prevented the development of duodenal ulcers in response to DDC. These results suggest that the mucosal antioxidative system including SOD may play a role in the regulatory process of alkaline secretion and contribute to the mucosal defensive ability in the duodenum. The insufficiency of this system may be involved in the pathogenesis of DDC-induced duodenal ulcers. Diethyldithiocarbamate (DDC), a potent metal chelator, is known to induce damage in the gastrointestinal mucosa in rats (1, 2). Re cently, we found that repeated administration of DDC to fed rats produced penetrating ulcers in the duodenum with a high incidence (3). Although inhibition of copper modulated cytosolic superoxide dismutase (SOD) is thought to be a significant factor in the pathogenesis of this toxicity, the precise mechanism remains unknown. Since the anti oxidative system including SOD may play a role in maintaining the functional integrity of these organs, the pathogenesis of DDC-in duced toxicity might involve the functional dis orders related to the insufficiency of this sys tem. We have previously shown that the im pairment of alkaline secretion is commonly in volved in the mechanism of experimental pro duction of duodenal ulcers as induced by mepirizole, antiinflammatory drugs or digi toxin (4-7). Thus, it is of interest to study the relationship between the antioxidative system and duodenal alkaline secretion.In the present study, we examined the effects of DDC and antioxidative drugs on duodenal alkaline secretion in the rat to in vestigate (a) the pathogenesis of DDC-induced duodenal ulcers and (b) the role of the anti oxidative system in duodenal alkaline secretion.

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“…After reperfusion, ROS are generated from the xanthine oxidase system and potentiate neutrophils, leading to tissue lipid peroxidation (LPO), which in association with gastric acid secretions results in cellular damage and death (Rao and Vijayakumar, 2007). Some antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) protect gastric tissue against IR injury by inhibiting the expression of ROS and decreases the levels of the superoxide anion (O 2 -) and hydrogen peroxide (H 2 O 2 ) (Ogino et al, 1988;Stein et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

The antiulcer and antioxidant mechanisms of the butanolic fraction extract obtained from Bauhinia forficata leaves: A medicinal plant frequently used in Brazilian folk medicine

Rey¹,

Guimarães²,

Toledo³

et al. 2018

J. Med. Plants Res.

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The objectives of this work were to evaluate the antiulcer activity, antioxidant mechanisms, phytochemical analysis and ecotoxicological risk of the butanolic fraction (ButFr) obtained from the leaf extracts of Bauhinia forficata. In an ischemia-reperfusion (IR), gastric ulcer model with doses 12.5 and 6.25 mg kg -1 promoted significant decreases in the ulcerative lesion area (ULA) by 50% (p<0.001) and 46% (p<0.001), respectively. Regarding the antioxidant mechanisms, the dose of 6.25 mg kg -1 promoted a significant increase in SOD (41%), GPx (62.7%) and GR (54.5%) activities (p <0.001) when compared to the negative control. 38% reduction in Myeloperoxidase activity (MPO) activity was also observed as well as 35.5% reduction in the LPO index when compared to the negative control (p <0.001). Phytochemical analysis demonstrated the presence of flavonoids (kaempferitrin and rutin) in ButFr, compounds responsible for the pharmacological activities observed. Conclusively the ButFr has antiulcer activity via antioxidant mechanisms.

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Gastric Mucosal Protection and Superoxide Dismutase

Cited by 25 publications

References 0 publications

Diethyldithiocarbamate, a Superoxide Dismutase Inhibitor, Reduces Indomethacin-lnduced Gastric Lesions in Rats

Diethyldithiocarbamate, a Superoxide Dismutase Inhibitor, Reduces Indomethacin-lnduced Gastric Lesions in Rats

Duodenal Ulcers Induced by Diethyldithiocarbamate, a Superoxide Dismutase Inhibitor, in the Rat: Role of Antioxidative System in the Pathogenesis.

The antiulcer and antioxidant mechanisms of the butanolic fraction extract obtained from Bauhinia forficata leaves: A medicinal plant frequently used in Brazilian folk medicine

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