Adrenomedullin fails to reduce cadmium-induced oxidative damage in rat liver.
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 CdCl(2) in drinking water for four weeks. One of these groups received 3000 ng/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.
Eşrefoglu
Mukaddes
M
Department of Histology and Embryology, Medical Faculty, Inonu University, Malatya 44280, Turkey. mdrmukaddes@yahoo.com
Gül
Mehmet
M
Dogru
Mehmet Ilker
MI
Dogru
Arzu
A
Yürekli
Muhittin
M
D053607:Adrenomedullin / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D019256:Cadmium Chloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005980:Glutathione Reductase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D008054:Lipid Peroxides; D053607:Adrenomedullin; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D019256:Cadmium Chloride