Recent studies have demonstrated that chronic cadmium administration induces oxidative stress. In the present study, we investigated the possible therapeutic effect of adrenomedullin, a potent antioxidant, in cadmium-induced morphological, ultrastructural and biochemical alterations. Two groups of rats were exposed to 100 ppm of CdCl2 in drinking water for four weeks. One of these groups received 3000ng/kg body weight of adrenomedullin (AdM) intraperitoneally during the last week. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides and changes in the antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPx) and glutathione reductase (GSH) levels. Hepatic damage score was significantly higher in Cd-administered rats than those of controls (p < 0.005). Cd-induced ultrastructural changes in hepatocytes included focal parenchymal cell necrosis, dilatation of rough endoplasmic reticulum, proliferation of lysosomes and mitochondrial degeneration. Hepatic damage was accompanied by significant increase in tissue MDA level (p < 0.05) and significant decrease in tissue GSH level (p < 0.05), and SOD and GPx activities (p, > 0.05, p > 0.005, respectively). Adrenomedullin failed to restore the light and electron microscopic, and biochemical changes. We conclude that although we administered a high dose of adrenomedullin, it failed to reduce cadmium-induced hepatic damage probably because of the irreversibility of Cd-induced hepatic injury. (c) 2006 Elsevier GmbH. All rights reserved.