Targeting NLRP3 inflammasome activation in styrene-induced ototoxicity: comparative efficacy of rosmarinic acid and anakinra in mitigating oxidative and inflammatory damage.

Objective: Styrene is a known ototoxic drug, causing increased oxidative stress and inflammation in cochlear structures. The aim of this study is exploring the possible involvement of NRLP3 inflammasome in mediating the interplay between oxidative stress and inflammation in a model of styrene ototoxicity and to compare the effectiveness of two therapeutic strategies.

Design: Styrene was administered 400 mg/kg, 5 days a week for 3 consecutive weeks in Wistar rats. An antioxidant (rosmarinic acid, 10 mg/kg), and an anti-inflammatory (anakinra, 30 mg/kg) drugs were used to evaluate the protective effects on auditory function. At the end of treatments functional, morphological and molecular analyses were used to study the mechanisms underlying ototoxicity and otoprotection. Study sample: 66 male adult Wistar rats. Results: Both antioxidant and anti-inflammatory treatments significantly reduced oxidative stress, NLRP3 inflammasome activation, and inflammatory markers. However, anakinra provided the best protective effect, with earlier hearing recovery and greater suppression of inflammation.

Study sample: 66 male adult Wistar rats of 2 months of age.

Results: Functional and molecular analyses revealed that both treatments significantly reduced oxidative stress, NLRP3 inflammasome activation, and inflammatory markers. However, anakinra provided the best protective effect, as evidenced by earlier auditory threshold recovery and greater suppression of inflammation. These findings underscore the pivotal role of inflammation in styrene-induced ototoxicity, highlighting NLRP3 inflammasome activation as a central mediator linking oxidative and inflammatory damage.

Conclusions: Our results suggest that targeting inflammation provides a more comprehensive and timely intervention for styrene ototoxicity. The dual mechanism of action of anakinra (reducing NLRP3 levels and directly modulating IL-1β) makes it a promising candidate for mitigating cochlear damage caused by environmental and toxic insults.