Highlights

• This study demonstrated that epalrestat alone aggravates RA symptoms by increasing the levels of toxic aldehydes, such as 4-HNE.
• Combining epalrestat with N-acetylcysteine (NAC) effectively reduces the accumulation of toxic aldehydes and improves arthritic conditions in AIA rats.
• This combined therapy represents a potential and safer treatment approach for RA patients, especially those with diabetic complications.

Summary

Epalrestat is an aldose reductase inhibitor (ARI) used for diabetic neuropathy in China and Japan. This research investigated the effectiveness of epalrestat in treating rheumatoid arthritis (RA).

Initially, epalrestat alone was found to aggravate RA symptoms in an adjuvant-induced arthritis (AIA) model due to an increase in 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) levels. These compounds are associated with inflammation and oxidative stress. However, when scientists combined epalrestat with N-acetylcysteine (NAC), an antioxidant, these harmful compounds and inflammatory cytokines were significantly reduced. This led to an improvement in the arthritic condition.

These findings suggest that while epalrestat alone may worsen RA symptoms due to the accumulation of toxic aldehydes, its combination with NAC mitigates this effect and enhances the drug’s anti-arthritic potential. Combined therapy could offer a novel and safer treatment option for RA, especially in patients who also require the management of diabetic complications.

L. Wang et al., “N -Acetylcysteine overcomes epalrestat-mediated increase of toxic 4-hydroxy-2-nonenal and potentiates the anti-arthritic effect of epalrestat in AIA model,” Int. J. Biol. Sci., vol. 19, no. 13, pp. 4082–4102, 2023, doi: