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Parasher, Gulshan; Frenklakh, L; Goodman,; Siddiqui, Tahmeena; Nandi, Jyotirmoy; Levine, Robert A.

doi:10.1023/a:1012304710187

Cited by 16 publications

(1 citation statement)

References 19 publications

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“…45) NOx production is a contributing factor in the pathogenesis of enteropathy. 31,32,46,47) It has been reported that the iNOS is closely related to the development of intestinal microvascular injury induced by indomethacin. 47) OGT influences microcirculatory blood flow, which is one of the mechanisms responsible for the efficacy of OGT.…”

Section: Fig 10 Localization Of Cox-2 Expressing Cellsmentioning

confidence: 99%

An Herbal Medicine Orengedokuto Prevents Indomethacin-Induced Enteropathy

Miura

Fukutake

Yamamoto

et al. 2007

Biological & Pharmaceutical Bulletin

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Prostaglandin E2 (PGE2) is a key regulator of gastrointestinal, immunological, and mucosal homeostasis. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the prostaglandin-producing enzyme cyclooxygenases (COXs), and can induce serious complications, such as gastrointestinal damage, with long-term treatment. Orengedokuto (OGT), a Japanese traditional herbal medicine (Kampo medicine), is effective in various animal models of enteropathy. In the present study we examined whether OGT prevents enteropathy induced by NSAIDs in mice. Ulceration in the small intestine was induced with 2 subcutaneous injections of indomethacin (20 mg/kg body weight). Orally administered OGT prevented or reduced lethality, intestinal lesions, bleeding, increased serum nitrate/nitrite levels, and reduction of mucosal PGE2 induced by indomethacin. These beneficial effects of OGT were accompanied by increased production of PGE2 and interleukin 10 by isolated lamina propria mononuclear cells; COX-2 in these cells may be a major source of PGE2 in normal intestines. These findings suggest that OGT could be an effective therapeutic agent for the treatment of inflammatory bowel disease and adverse reactions to NSAIDs.Key words nonsteroidal anti-inflammatory drug; interleukin 10; herbal medicine; inflammatory bowel disease; prostaglandin E2

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Section: Fig 10 Localization Of Cox-2 Expressing Cellsmentioning

confidence: 99%

An Herbal Medicine Orengedokuto Prevents Indomethacin-Induced Enteropathy

Miura

Fukutake

Yamamoto

et al. 2007

Biological & Pharmaceutical Bulletin

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Inhibition of iNOS with 1400W improves contractile function and alters nos gene and protein expression in reperfused skeletal muscle

Patel

Allen

et al. 2004

Microsurgery

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This study examined the effects of 1400W, an inhibitor of inducible nitric oxide (iNOS), on contractile function and iNOS expression in reperfused skeletal muscle. The right extensor digitorum longus (EDL) muscle of 104 rats underwent a sham operation or 3-h ischemia followed by 3-h or 24-h reperfusion (I/R). Rats received 3 mg/kg 1400W, 10 mg/kg 1400W, or water subcutaneously. Results showed that EDL contractile function in both 1400W-treated groups significantly outperformed the controls at 24-h but not at 3-h reperfusion. Although iNOS expression increased in all three I/R groups during reperfusion, a significantly smaller increase was found in 1400W-treated muscles after 3-h reperfusion, and more dramatically so after 24-h reperfusion. Our results indicate that inhibition of iNOS preserved the contractile function in reperfused skeletal muscle, perhaps via downregulating iNOS expression. Protection by 1400W at 24-h reperfusion suggests that the role of iNOS in exaggerating reperfusion injury is more prominent in the later stages of injury.

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Addition of nitric oxide donor S-nitroso-N-acetylcysteine to selective iNOS inhibitor 1400W further improves contractile function in reperfused skeletal muscle

Barker

Cai

et al. 2005

Microsurgery

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This study examines the effects of combination therapy with the nitric oxide (NO) donor S-nitroso-N-acetylcysteine (SNAC) and the iNOS inhibitor N-(3-(aminomethyl)benzyl) acetamidine (1400W) on contractile function in reperfused rat skeletal muscle. The right extensor digitorum longus (EDL) muscles of 104 rats were subjected to 3 h of ischemia followed by reperfusion times of 3 h, 24 h, and 7 days. For each time period, rats were further divided into sham operation, control, 1400W only, and 1400W plus SNAC groups. In vitro muscle contractile functional testing was performed in an organ chamber with electrical stimulation. The results showed that twitch and isometric tetanic forces were significantly improved in the 1400W-alone group compared to controls for 24 h and 7 days, but not 3 h of reperfusion. However, all three time periods of reperfusion showed that combination treatment of 1400W + SNAC significantly improved muscle contractile force compared to both control and 1400W-only groups. This corresponded to the decreased tissue necrosis and inflammation seen with combination therapy histologically. Our results demonstrate that combination treatment of 1400W + SNAC promotes functional recovery in reperfused skeletal muscle, supporting that manipulation of NO levels with a NO donor and an iNOS inhibitor is more beneficial than either treatment in isolation.

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Untitled

Cited by 16 publications

References 19 publications

An Herbal Medicine Orengedokuto Prevents Indomethacin-Induced Enteropathy

An Herbal Medicine Orengedokuto Prevents Indomethacin-Induced Enteropathy

Inhibition of iNOS with 1400W improves contractile function and alters nos gene and protein expression in reperfused skeletal muscle

Addition of nitric oxide donor S-nitroso-N-acetylcysteine to selective iNOS inhibitor 1400W further improves contractile function in reperfused skeletal muscle

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