Cadmium from smoking increases oxidative stress and metal imbalance in osteoarthritis.

Knee osteoarthritis (OA) is a leading cause of disability worldwide. Oxidative stress (OS), enhanced by exposure to heavy metals such as cadmium (Cd), may contribute to its progression. Cd, present in tobacco smoke, disrupts chondrocyte viability, redox balance, and essential metal homeostasis. This study aimed to determine whether Cd exposure, particularly through smoking, influences the development and severity of knee OA by affecting antioxidant defense, metallothioneins (MTs) expression, arginase II activity, and trace metal levels in blood, synovial fluid (SF), and cartilage. Fifty-one OA patients were stratified by smoking status (non-smokers, ex-smokers, smokers). Cd and other metals were quantified by ICP-MS, along with OS markers (MDA, MGO, AOPPs), antioxidant enzymes (GST, GGT, CAT), prooxidant enzymes (MPO, arginase II), and metallothinein-1A and 2A (MT-1A/2A) levels. Non-parametric tests assessed correlations between Cd and redox markers. Smokers exhibited higher Cd in blood (0.34 ng/mL) and cartilage (26.07 ng/g), with increased GST, GGT, MDA, and AOPPs. Cd correlated positively with MDA (rho = 0.319, P = 0.033). In SF, elevated CAT, GGT, and arginase II activity were found in patients with high Cd levels (Q3), alongside increased MT-2A expression in smokers (P = 0.018). Cd exposure was also linked to an imbalance of essential metals such as selenium (Se). These findings suggest that Cd, mainly from smoking, exacerbates OS, alters redox enzyme activity, induces MT-2A, and disrupts metal homeostasis, potentially mediating OA pathogenesis. Longitudinal studies are warranted to confirm its causal role in disease progression.