# Resveratrol and Its Nitric Oxide–Donor Hybrid as an Emerging Therapy for Oxidative-Stress-Driven Priapism in Sickle Cell Disease

## TL;DR

This review explores resveratrol and its NO-donor hybrids as potential treatments for priapism in sickle cell disease by targeting oxidative stress and NO dysregulation.

## Contribution

The paper highlights resveratrol and its NO-donor hybrids as novel therapeutic candidates for oxidative-stress-driven priapism in SCD.

## Key findings

- Resveratrol and its NO-donor hybrids show preclinical promise in addressing oxidative stress and NO dysregulation in SCD-related priapism.
- Combining resveratrol with existing treatments may enhance therapeutic outcomes for priapism in SCD.
- Translational challenges remain in moving resveratrol-based therapies from preclinical to clinical use.

## Abstract

Priapism is a frequent and debilitating complication in patients with sickle cell disease (SCD), characterized by recurrent ischemic episodes that can culminate in fibrosis of the erectile tissue and irreversible erectile dysfunction. Despite significant advancements in the management of acute episodes, current therapies remain largely ineffective in preventing recurrences, emphasizing the need for novel strategies that target the underlying pathophysiology. This narrative review describes the mechanistic links between oxidative stress and nitric oxide (NO) dysregulation in the pathogenesis of SCD-associated priapism, with a particular focus on the NO–cyclic guanosine monophosphate (cGMP)–phosphodiesterase type 5 (PDE5) signaling axis. We analyze preclinical evidence supporting resveratrol, a natural polyphenolic compound, as well as its NO-donor hybrid derivatives, as emerging therapeutic candidates. Additionally, we discuss the potential of combining resveratrol with current treatment approaches, and address the translational challenges that must be overcome to move from preclinical data to clinical application. Taken together, the evidence presented in this review supports resveratrol-based therapies as a promising approach for oxidative-stress-driven priapism in SCD and delineates critical perspectives for their further investigation.