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Niclosamide attenuates erectile dysfunction and corporal fibrosis via reversal of Smad signaling in diabetic rat model. | LitMetric

AI Article Synopsis

  • - The study investigates the effects of Niclosamide, an antihelmintic drug, on erectile dysfunction caused by diabetes (DMED) in a rat model, focusing on its antifibrotic properties and influence on Smad2/3 signaling.
  • - Male rats were induced with diabetes and treated with Niclosamide for four weeks to assess changes in erectile function and tissue composition, evaluating parameters like intracavernous pressure (ICP) and fibrosis levels.
  • - Results showed that Niclosamide significantly improved erectile function and reversed fibrotic changes in the penile tissues of diabetic rats, indicating its potential as a treatment for DMED.

Article Abstract

Background: Diabetes mellitus-induced erectile dysfunction (DMED) is a common urological complication of diabetes, and current drugs often fail to provide an effective treatment. Smad2/3 signaling-mediated corporal fibrosis has a critical role in the molecular basis of DMED.

Aim: We investigated the effect of Niclosamide (Nic), an antihelmintic drug with antifibrotic effects, on erectile function in a rat DMED model.

Methods: Male Sprague Dawley rats were injected intraperitoneally (i.p) with streptozotocin (75 mg/kg) to induce diabetes. At week 8, both diabetic and nondiabetic rats were treated with Nic (10 mg·kg-1/day; i.p) or vehicle for 4 weeks. At week 12, erectile function was evaluated as intracavernous pressure (ICP) response to the electrical stimulation of the cavernous nerve (CN). Penile tissues were harvested for Masson's trichrome staining or western blotting to determine corporal fibrosis and Smad2/3 pathway-related protein expression, respectively.

Outcomes: At the end of the experimental protocol, in vivo erectile function was assessed by measuring the ratio of ICP/ mean arterial pressure (MAP) and total ICP following CN stimulation. Smooth muscle content and collagen fibers were evaluated by Masson's trichrome staining of the penile tissues. The expressions of fibrosis-related proteins (Smad2, Smad3, fibronectin) were determined using western blotting in the penile tissues.

Results: Erectile function, as determined by the maximum ICP/MAP and total ICP/MAP ratios, was drastically decreased in diabetic rats. Corporal tissues of diabetic rats were severely fibrotic with a significant increase in collagen fibers and a marked reduction in smooth muscle content. Also, the protein expressions of phosphorylated (p-)Smad2, p-Smad3 and fibronectin were significantly increased in the penis of diabetic rats. Both functional and molecular alterations in DMED were effectively reversed by Nic-treated diabetic rats without a glycemic alteration.

Clinical Implications: Nic could be a promising candidate for the treatment of DMED due to its antifibrotic effects.

Strengths And Limitations: The present study provides the first evidence that Nic has beneficial effect on erectile dysfunction by attenuating corporal fibrosis in a rat model of DMED. The effect of Nic on penile endothelial function and the other potential underlying mechanisms needs to be further elucidated.

Conclusions: Nic improved erectile function in DMED rats possibly suppressing penile fibrosis by inhibiting Smad2/3 signaling. These results suggest a potential therapeutic repurposing of Nic as an adjuvant treatment in DMED.

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Source
http://dx.doi.org/10.1093/jsxmed/qdae129DOI Listing

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