Antioxidant Effects of Photodegradation Product of Nifedipine

Horinouchi, Yuya; Tsuchiya, Koichiro; Taoka, Chiaki; Tajima, Soichiro; Kihira, Yoshitaka; Matsuda, Yuko; Shishido, Kozo; Yoshida, Masahiro; Hamano, Shuichi; Kawazoe, Kazuyoshi; Ikeda, Yasumasa; Ishizawa, Keisuke; Tomita, Shuhei; Takahashi, Toshiaki

doi:10.1248/cpb.59.208

Cited by 18 publications

(29 citation statements)

References 61 publications

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“…NO-NIF has a unique, strong, and long-lasting radical scavenging activity through its reaction with unsaturated fatty acids within the cell membrane, and its protective effects on endothelial cells [5,6]. In the present study, we found that NO-NIF suppressed pharmacologically induced aortic aneurysm formation.…”

Section: Discussionsupporting

confidence: 62%

“…We showed that it suppresses N ω -nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced ICAM-1 expression in aortic endothelial cells and urinary protein elevation in rats, without changing blood pressure [5]. We have suggested that NO-NIF generates strong radical scavenging activity through its reaction with unsaturated fatty acids within the cell membrane [6]. Our in vitro studies have shown that NO-NIF suppresses cumene hydroperoxide-induced membrane peroxidation and cell death in endothelial cells [5].…”

Section: Introductionmentioning

confidence: 99%

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Nitrosonifedipine, a Photodegradation Product of Nifedipine, Suppresses Pharmacologically Induced Aortic Aneurysm Formation

et al. 2018

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Background/Aims: We have reported that nitrosonifedipine (NO-NIF), a photodegradation product of nifedipine, has strong antioxidant and endothelial protective effects, and can suppress several cardiovascular diseases in animal models. The objective of the present study was to investigate the effects of NO-NIF on aortic aneurysm formation. Methods: The mice were infused with β-aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. The oxidative stress was measured by dihydroethidium staining and nitrotyrosine staining. The expressions of inflammation-related genes were assessed by quantitative real-time PCR and immunohistochemical staining. To clarify the mechanisms of how NO-NIF suppresses vascular cell adhesion molecule (VCAM)-1, endothelial cells were used in in vitro system. Results: NO-NIF suppressed pharmacologically induced the aortic aneurysm formation and aortic expansion without blood pressure changes. NO-NIF suppressed elastin degradation and matrix metalloproteinase-2 mRNA expression. NO-NIF suppressed the reactive oxygen species-cyclophilin A positive feedback loop. Upregulated mRNA expressions of inflammation-related genes and endothelial VCAM-1 were suppressed by NO-NIF co-treatment in aortae. Conclusion: NO-NIF has the potential to be a new, nifedipine-derived therapeutic drug for suppressing aortic aneurysm formation by directly improving aortic structure with its strong ability to reduce oxidative stress and inflammation.

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Section: Discussionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Nitrosonifedipine, a Photodegradation Product of Nifedipine, Suppresses Pharmacologically Induced Aortic Aneurysm Formation

et al. 2018

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“…NO-NIF does not have a calcium channel blocking effect ; however, it has a strong and unique radical scavenging ability. It reacts with lipid-derived radicals in vitro and participates in radical scavenging activities in the cell membrane (8). We focused on this unique radical scavenging activity and previously investigated the effects of NO-NIF in some oxidative -stress-related cardiorenal diseases using animal models (10 -12).…”

Section: Antioxidative Effect Of Nifedipine Photodegradation Product mentioning

confidence: 99%

“…Interestingly, a mixture of NO-NIF and unsaturated fatty acids exhibited an extremely stronger radical scavenging activity than NO-NIF alone did (8). Furthermore, an electron paramagnetic resonance (EPR) method revealed that NO-NIF could be converted to its radical form through an in vitro reaction with unsaturated fatty acids, which are abundant in cell membranes, but not with saturated fatty acids.…”

Section: Antioxidative Effect Of Nifedipine Photodegradation Product mentioning

confidence: 99%

“…In addition, characteristic aeolotropic triplet signals suggested that the radical stayed within the cell membrane. Thus, it was proposed that NO-NIF shows a unique strong radical scavenging activity that is prolonged by reacting with unsaturated fatty acids, after which it is converted to its radical form in the cell membrane (8).…”

Section: Antioxidative Effect Of Nifedipine Photodegradation Product mentioning

confidence: 99%

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Pharmacological approach for drug repositioning against cardiorenal diseases

et al. 2017

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: New applications of approved clinically used drugs are being discovered. Drug repositioning is a proposed strategy for developing these drugs as therapeutic agents for different diseases. Currently, approximately 2000 drugs are used in Japan. However, the compound targets and pathways involved in the pharmacological actions of 70-80% of these drugs have not been adequately clarified. Pharmacological examination of approved drugs is an important task in drug repositioning and vital for improving drug development efficiency. This review reports that angiotensin II type 1 receptor blockers show receptor-independent effects against reactive oxygen species generation in renal cells. Additionally, nitrosonifedipine has an antioxidative effect and protects endothelial cells against oxidative stress, and pioglitazone has multiple effects that improve dysfunctions in vascular control regulated by adrenergic and calcitonin gene-related peptide-containing nerves in animal models of diabetes. These data suggest that some approved drugs could be useful for treating cardiorenal diseases. Since cardiorenal diseases are likely to have chronic pathological conditions and require chronic drug administration, highly safe drugs are needed. Compared to newly developed drugs, drug repositioning of approved drugs with safety information is considered a particularly useful technique for searching new treatments for cardiorenal diseases.

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Comparative Bioequivalence and Food Effect of Two Formulations of 30‐mg Nifedipine Controlled‐Release Tablets in Healthy Chinese Adults

Zhang,

Wang,

Wang

et al. 2024

Clinical Pharm in Drug Dev

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Nifedipine is a potent antihypertensive medication classified as a dihydropyridine calcium channel blocker. The objective of this trial was to assess the bioequivalence of a 30‐mg nifedipine controlled‐release tablet and a reference drug in a cohort of healthy Chinese individuals. Two independent open‐label, randomized, single‐dose, crossover studies were conducted, 1 under fasting conditions (N = 44, with 1 participant dropping out midway) and the other under fed conditions (N = 44, with 4 participants dropping out midway). Plasma concentrations of nifedipine were determined using liquid chromatography‐mass spectrometry, and pharmacokinetic (PK) parameters were calculated using noncompartmental analysis with Phoenix WinNonlin 8.0 software. In both fasting and fed studies, reasonable bioequivalence was observed for the PK parameters of both the test product and the reference drug. A good safety profile was demonstrated for both the test product and reference drug, with no serious adverse events reported, and both were similarly well tolerated. An important observation with food coadministration was that systemic exposure to nifedipine (based on area under the curve, AUC0‐∞) was reduced by approximately 12%. The bioequivalence of the test product and reference drug under fasting/fed conditions in healthy subjects in China was demonstrated by the study results.

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Antioxidant Effects of Photodegradation Product of Nifedipine

Cited by 18 publications

References 61 publications

Nitrosonifedipine, a Photodegradation Product of Nifedipine, Suppresses Pharmacologically Induced Aortic Aneurysm Formation

Nitrosonifedipine, a Photodegradation Product of Nifedipine, Suppresses Pharmacologically Induced Aortic Aneurysm Formation

Pharmacological approach for drug repositioning against cardiorenal diseases

Comparative Bioequivalence and Food Effect of Two Formulations of 30‐mg Nifedipine Controlled‐Release Tablets in Healthy Chinese Adults

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