Monoterpene Ketone Piperitone Mitigates Cataractogenesis via Antioxidant Enhancement, Redox Modulation, and Anti-inflammatory Mechanisms in a Selenite-induced Rat Model

Background: Cataracts remain the foremost cause of preventable blindness globally, with oxidative stress serving as a central contributor to their pathogenesis. Given the limited accessibility of surgical intervention in many populations, there is a pressing need for effective non-surgical therapeutic alternatives. We aimed to explore the protective role of piperitone against cataract development in experimental rodents. Objectives: We aimed to explore the protective role of piperitone against cataract development in experimental rodents. Materials and Methods: In the present study, cataracts were experimentally triggered in rat pups via a solitary subcutaneous dose of sodium selenite on post-natal day 12. Piperitone was administered at two different doses to evaluate its potential in mitigating cataractogenesis. Antioxidant capacity, oxidative stress markers, and indicators of lens protein oxidation were quantified to determine the compound’s antioxidative efficacy. Additionally, lens ascorbic acid levels and total calcium content were measured to assess their impact on lens clarity. Inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor kappa B were measured to investigate piperitone’s anti-inflammatory action. Furthermore, key components of the nuclear factor erythroid 2-related factor 2 (Nrf2) redox signaling pathway were evaluated to elucidate the underlying antioxidant mechanism. Lens opacification scores were recorded as a direct measure of cataract progression. Results: The findings revealed that piperitone significantly enhanced antioxidant defenses, reduced oxidative damage and protein modification in the lens, and suppressed inflammatory signaling. It also modulated redox homeostasis via activation of the Nrf2 pathway and led to a marked reduction in lens opacity. Conclusion: Collectively, our data support the therapeutic efficacy of piperitone as an antioxidant agent for the prevention or delay of cataract development.