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34,35 Controversially, another research mentioned that serum SOD2 levels increased in patients with OA, indicating an elevated oxidative stress related with OA

[ 478 ] However, many natural NRF2 agonists are unstable under physiological conditions, with extremely low bioavailability, [ 479 ] and their reactions with cysteine residues are often irreversible, which can cause abnormal and persistent activation of NRF2 and may lead to carcinogenesis, [ 480 ] severely limiting their clinical application

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