Toxicological aspects of feprazone, a new nonsteroidal anti-inflammatory drug

Koyama, Tamotsu; Izawa, Yohei; Wada, Hiroshi; Makita, Tokutaro; Hashimoto, Yoshinobu; Enomoto, Makoto

doi:10.1016/0041-008x(82)90222-8

Cited by 4 publications

(4 citation statements)

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“…In our future work, the mechanism will be further confirmed by introducing the SOX-4-overexpressed chondrocytes. Feprazone has been used for pain control for a long time, but its toxicity has been reported . The current study provides molecular evidence of its therapeutic potential, but its effect in vivo remains to be investigated.…”

Section: Discussionmentioning

confidence: 85%

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Feprazone Ameliorates TNF-α-Induced Loss of Aggrecan via Inhibition of the SOX-4/ADAMTS-5 Signaling Pathway

Xiong

Liu

et al. 2021

ACS Omega

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Background: Arthritis is a cartilage degenerative disease that is mainly induced by the degradation of the cartilage extracellular matrix (ECM), which is found to be regulated by the expression level of a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMT-5), an enzyme degrading Aggrecans in the ECM. Feprazone is a classic nonsteroidal anti-inflammatory drug with promising efficacy in arthritis. The present study aims to investigate the protective effect of Feprazone on the degraded Aggrecan in the human chondrocytes induced with tumor necrosis factor-α (TNF-α) and to clarify the underlying mechanism. Methods: To investigate the effect of Feprazone, the CHON-001 chondrocytes were stimulated with TNF-α (10 ng/mL) in the presence or absence of Feprazone (3, 6 μM) for 24 h. Mitochondrial membrane potential was evaluated using the Rhodamine 123 assay. The gene expressions of interleukin-1β (IL-1β), interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and ADAMTS-5 in the treated chondrocytes were detected using real-time quantitative polymerase chain reaction (qRT-PCR), and the protein levels of these targets were determined using enzyme-linked immunosorbent assay (ELISA). SOX-4 was knocked down by transfecting the siRNA into the chondrocytes. Western blot analysis was utilized to evaluate the expression levels of SOX-4, Aggrecan, and protein kinase C (PKCα). Results: First, the reduced mitochondrial membrane potential (ΔΨm) and secretion of proinflammatory factors (IL-1β, IL-8, and MCP-1) induced by TNF-α were significantly reversed by treatment with Feprazone. Second, the expression of Aggrecan was significantly decreased by stimulation with TNF-α via upregulation of ADAMTS-5 but was dramatically reversed by the introduction of Feprazone. Third, we found that TNF-α elevated the expression of ADAMTS-5 by upregulating SOX-4, which was observed to be related to the activation of PKCα. Lastly, the elevated expression of SOX-4 induced by TNF-α was significantly reversed by Feprazone. Conclusions: Feprazone might ameliorate TNF-α-induced loss of Aggrecan via the inhibition of the SOX-4/ADAMTS-5 signaling pathway.

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Section: Discussionmentioning

confidence: 85%

“…Feprazone has been used for pain control for a long time, but its toxicity has been reported. 39 The current study provides molecular evidence of its therapeutic potential, but its effect in vivo remains to be investigated.…”

Section: ■ Discussionmentioning

confidence: 97%

Feprazone Ameliorates TNF-α-Induced Loss of Aggrecan via Inhibition of the SOX-4/ADAMTS-5 Signaling Pathway

Xiong

Liu

et al. 2021

ACS Omega

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“…Він про-являє протизапальну, жарознижуючу та знебо-люючу дію [1] та інтенсивно використовується при лікуванні хвороби Бехтєрєва, ревматоїдно-го артриту та синдрому Рейтера. Близьким за хі-мічною структурою є препарат «Фепразон» 2, який характеризується протизапальними властивостя-ми і застосовується при лікуванні захворювань суглобів опорно-рухового апарату та м'язів [2].…”

Section: Issn 2308-8303unclassified

“…Також відомо, що речовини з піразолідиндіо-новим фрагментом схильні проявляти антибак-теріальну та фунгіцидну активність [3]. Тому ство-рення нових препаратів шляхом модифікації пі-разолідиндіонового циклу є цікавим і перспек-тивним напрямком сучасних досліджень в галу-зі органічної та фармацевтичної хімії.…”

Section: Issn 2308-8303unclassified