Scavenging effect of nicorandil on free radicals and lipid peroxide in streptozotocin-induced diabetic rats

Mano, Takamitsu; Shinohara, Rikio; Nagasaka, Akio; Nakagawa, Hiroo; Uchimura, Keiko; Hayashi, Rina; Nakano, Itsuko; Tsugawa, Toru; Watanabe, Fumio; Kobayashi, Takako; Fujiwara, Kentaro; Nakai, Asami; Itoh, Mitsuyasu

doi:10.1016/s0026-0495(00)80003-7

Cited by 56 publications

(57 citation statements)

References 29 publications

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“…In addition, mild body weight loss was observed with high-dose nicorandil treatment. This finding is consistent with our laboratory's previous studies (9,19).…”

Section: Nicorandil Reduces Albuminuria Glomerular and Tubulointerssupporting

confidence: 94%

Nicorandil, a K_atp channel opener, alleviates chronic renal injury by targeting podocytes and macrophages

Tamura

Tanabe

Kitagawa

et al. 2012

American Journal of Physiology-Renal Physiology

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“…In addition, mild body weight loss was observed with high-dose nicorandil treatment. This finding is consistent with our laboratory's previous studies (9,19).…”

Section: Nicorandil Reduces Albuminuria Glomerular and Tubulointerssupporting

confidence: 94%

Nicorandil, a K_atp channel opener, alleviates chronic renal injury by targeting podocytes and macrophages

Tamura

Tanabe

Kitagawa

et al. 2012

American Journal of Physiology-Renal Physiology

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“…The antioxidant effects of gliclazide may attenuate ventricular mass. Furthermore, nicorandil possesses anti-free radical characteristics, since the nicotinamide moiety of its molecular structure is a known hydroxyl radical scavenger and an inhibitory effect on superoxide anion production (21). Thus the groups treated with nicorandil may attenuate ventricular mass by its antioxidant action.…”

Section: Discussionmentioning

confidence: 99%

Effects of sulfonylureas on left ventricular mass in type 2 diabetic patients

Lee¹,

Lin²,

Tsai³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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cardial ATP-sensitive potassium (KATP) channels have been implicated in attenuating cardiac hypertrophy by modulating endothelin-1 concentrations. Sulfonylureas differ in their affinity for cardiac KATP channels and therefore may vary in their effects on left ventricular (LV) mass. We sought to determine the differential effects of sulfonylureas on LV mass in type 2 diabetic patients. All patients had been taking glibenclamide for more than 3 mo before being randomized to either switch to an equipotent dose of gliclazide or continue glibenclamide. A total of consecutive 240 diabetic patients were randomized into glibenclamide, gliclazide, a combination of glibenclamide and nicorandil, or gliclazide and nicorandil for 6 mo. In the gliclazidetreated group, the LV mass index was significantly decreased compared with that in the glibenclamide-treated groups. Nicorandil administration significantly reduced LV mass in glibenclamide-treated patients compared with patients treated with glibenclamide alone. Measurements of endothelin-1 concentrations mirrored the functional status of KATP channel. Multivariate analysis revealed that regression of LV mass was significantly correlated only with the changes in endothelin-1 (P Ͻ 0.0001). Our results show that KATP channels may play a pathogenetic role, probably through an endothelin-1-dependent pathway, in diabetes mellitus-related ventricular hypertrophy. Patients treated with gliclazide may have a beneficial effect in attenuating ventricular mass. adenosine 5Ј-triphosphate-sensitive potassium channels; diabetes mellitus; glibenclamide; gliclazide; ventricular hypertrophy

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“…Nicorandil was reported to have free radical scavenging activity in in vitro studies [29][30][31][32] , but no reports have been published on the possible contribution of this property to its gastroprotective effect. In the present work, it has been found that nicorandil pretreatment significantly reduced the gastric mucosal MDA level, as compared to the saline-pretreated WIRS group.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the Mechanisms Underlying the Gastroprotective Effect of Nicorandil

Ismail

Khalifa²,

Hassan³

et al. 2006

Pharmacology

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Aim: This study investigated possible mechanisms underlying the gastroprotective effect of nicorandil on experimentally-induced gastric lesions in rats. Methods: Rats were randomly assigned to vehicle-, nicorandil (10 mg/kg)-, glibenclamide (6 mg/kg)-, nicorandil + glibenclamide- and cimetidine-pretreated groups, in addition to non-stressed control group, to demonstrate whether the K_ATPchannel opening contributed to nicorandil’s gastroprotection. Lesions were induced by water immersion-restraint stress (WIRS) and ulcer indices were determined. Gastric juice parameters (pH, acid output, pepsin and mucin concentrations) were determined. Another set of rats was divided into control, saline-pretreated and nicorandil (10 mg/kg)-pretreated groups. Rats underwent WIRS and their stomachs were used for determination of gastric mucosal lipid peroxides, histamine, PGE₂, and total nitrites levels. Results: Nicorandil displayed significant protection against gastric lesions formation, abolished by concomitant administration of glibenclamide. Nicorandil significantly reduced gastric acid and pepsin secretion, but upon coadministration with glibenclamide, these effects were blocked. Additionally, nicorandil significantly reduced gastric mucosal lipid peroxides and total nitrites, but did not affect PGE₂ and histamine levels. Conclusion: Results confirm a gastroprotective effect for nicorandil, the mechanism of which comprises K_ATP channel opening, free radical scavenging, decrease of pepsin and acid secretion and prevention of the detrimental rise in nitric oxide during WIRS.

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Scavenging effect of nicorandil on free radicals and lipid peroxide in streptozotocin-induced diabetic rats

Cited by 56 publications

References 29 publications

Nicorandil, a K_atp channel opener, alleviates chronic renal injury by targeting podocytes and macrophages

Nicorandil, a K_atp channel opener, alleviates chronic renal injury by targeting podocytes and macrophages

Effects of sulfonylureas on left ventricular mass in type 2 diabetic patients

Investigation of the Mechanisms Underlying the Gastroprotective Effect of Nicorandil

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Scavenging effect of nicorandil on free radicals and lipid peroxide in streptozotocin-induced diabetic rats

Cited by 56 publications

References 29 publications

Nicorandil, a Katp channel opener, alleviates chronic renal injury by targeting podocytes and macrophages

Nicorandil, a Katp channel opener, alleviates chronic renal injury by targeting podocytes and macrophages

Effects of sulfonylureas on left ventricular mass in type 2 diabetic patients

Investigation of the Mechanisms Underlying the Gastroprotective Effect of Nicorandil

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Product

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Nicorandil, a K_atp channel opener, alleviates chronic renal injury by targeting podocytes and macrophages

Nicorandil, a K_atp channel opener, alleviates chronic renal injury by targeting podocytes and macrophages