Differential Sensitivity of Endocrine and Non-Endocrine Tissues to Cadmium-Induced Lipid Peroxidation and the Protective Role of Melatonin ^†

Cadmium is a toxic heavy metal classified by the International Agency for Research on Cancer as a human carcinogen and recognized as an endocrine-disrupting chemical. The present study aimed to evaluate tissue-specific susceptibility to cadmium-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) and to assess the antioxidative effects of melatonin in porcine tissue homogenates representing endocrine (the thyroid and the ovary) and non-endocrine (the liver, the kidney, and the brain) organs. Homogenates were incubated with cadmium chloride (CdCl₂; 2.5–1000 µM) without/with melatonin (0.1–5.0 mM). Lipid peroxidation was assessed spectrophotometrically by measuring malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) levels. Cadmium significantly increased LPO in the liver (2.5–1000 μM) and in the kidney (25–1000 μM), whereas no prooxidative effect was observed in endocrine tissues or in the brain. Liver damage was mitigated by melatonin doses as low as 0.1 μM across the 250–1000 μM cadmium range, while protection in the kidney was limited to higher melatonin concentrations (2.5–5.0 mM) against damage induced by 100–1000 μM cadmium concentrations. The findings demonstrate pronounced tissue-specific differences in susceptibility to cadmium-induced oxidative stress and support the potential of melatonin as a preventive agent against heavy metal-induced oxidative stress, particularly in non-endocrine organs.