"Old is gold" hydralazine, a magic bullet for dry eye disease

Dry eye disease (DED) is a highly prevalent ocular condition characterized by insufficient tear production or poor tear quality, leading to inflammation, discomfort, and potential vision impairment. Current treatments, primarily artificial tears and limited prescription options like steroids, often provide only partial or temporary relief, underscoring the critical need for more effective and safer therapeutic strategies. A key pathological driver of DED is oxidative stress, which generates reactive aldehyde species (RASP) like malondialdehyde and 4-HNE. These cytotoxic electrophiles form adducts with cellular macromolecules, causing widespread damage. This work explores a therapeutic approach focused on scavenging RASP to mitigate this damage. Inspired by the known carbonyl-scavenging ability of the hydrazide group, we found hydralazine, an anti-hypertensive drug that contains highly nucleophilic hydrazide group can react rapidly with aldehydes to form stable, non-toxic products. This compound is engineered to be potent scavengers of RASP, offering a promising new avenue for the treatment of Dry Eye Disease by directly targeting a root cause of oxidative cellular damage.