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ACS Applied Electronic Materials

ACS Applied Electronic Materials

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Verapamil Attenuates the Severity of Tendinopathy by Mitigating Mitochondrial Dysfunction through the Activation of the Nrf2/HO-1 Pathway

Published:18 April 2024 DOI: 10.3390/biomedicines12040904
Zengguang Wang, Zhenglin Dong, Yiming Li, Xin-Ming Jiao, Yihao Liu, Hanwen Chang, Yaokai Gan

Abstract

Tendinopathy is a prevalent condition in orthopedics patients, exerting a profound impact on tendon functionality. However, its underlying mechanism remains elusive and the efficacy of pharmacological interventions continues to be suboptimal. Verapamil is a clinically used medicine with anti-inflammation and antioxidant functions. This investigation aimed to elucidate the impact of verapamil in tendinopathy and the underlying mechanisms through which verapamil ameliorates the severity of tendinopathy. In in vitro experiments, primary tenocytes were exposed to interleukin-1 beta (IL?1β) along with verapamil at a concentration of 5 μM. In addition, an in vivo rat tendinopathy model was induced through the localized injection of collagenase into the Achilles tendons of rats, and verapamil was injected into these tendons at a concentration of 5 μM. The in vitro findings highlighted the remarkable ability of verapamil to attenuate extracellular matrix degradation and apoptosis triggered by inflammation in tenocytes stimulated by IL?1β. Furthermore, verapamil was observed to significantly suppress the inflammation-related MAPK/NFκB pathway. Subsequent investigations revealed that verapamil exerts a remediating effect on mitochondrial dysfunction, which was achieved through activation of the Nrf2/HO-1 pathway. Nevertheless, the protective effect of verapamil was nullified with the utilization of the Nrf2 inhibitor ML385. In summary, the in vivo and in vitro results indicate that the administration of verapamil profoundly mitigates the severity of tendinopathy through suppression of inflammation and activation of the Nrf2/HO-1 pathway. These findings suggest that verapamil is a promising therapeutic agent for the treatment of tendinopathy, deserving further and expanded research.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
ML385 846557-71-9 C29H25N3O4S 154 suppliers $18.00-$2646.00
ML385 846557-71-9 C29H25N3O4S 154 suppliers $18.00-$2646.00
ML385 846557-71-9 C29H25N3O4S 154 suppliers $18.00-$2646.00
ML385 846557-71-9 C29H25N3O4S 154 suppliers $18.00-$2646.00
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