Enhancement of detoxification of xenobiotic aromatic amine dyes by N-acetyltransferase 1 (NAT1) enzyme on human keratinocytes cells through structural modification

The metabolic conversion of aromatic amines to N-acetylated forms in skin and keratinocytes depends on N-acetyltransferase-1 (NAT1). Common hair color ingredient such as para-phenylenediamine (PPD) causes allergic contact dermatitis. We explored how different electronic substituents on PPD aided NAT1 enzyme biotransform oxidative arylamine (AA) compounds G1-G13 by N-acetylation, NAT-1 activity assays, metabolism, and in vitro clearance investigations in human keratinocytes, while identifying NAT-1 protein levels by Western blot and qRT-PCR. Electron-donating groups (EDG) compounds G2,G3,and G8, N-acetylate at a higher rate (58–62 nmol/mg/min), increase NAT1 activity by 20–25 %, and showed 3.4–3.8 times faster elimination and clearance rates than electron withdrawing groups (EWG) compounds G6 and G11. We found that chemicals substituted with EDG at ortho position increase aromatic system electron density, improving N-acetylation and detoxification on HaCaT cells. Our research facilitates the effective identification of aromatic amine hair dyes characterized by rapid metabolism, detoxification, and environmental safety.