title: Adrenomedullin reduces antioxidant defense system and enhances kidney tissue damage in cadmium and lead exposed rats.
abstract: Adrenomedullin (AdM) is synthesized and secreted by a number of cells and tissue. AdM is a potent vasodilator but it is also considered a neuromodulator, an angiogenic factor, and a hormone regulator. AdM possess antiapoptotic, antioxidant, and antimicrobial properties. Heavy metals such as cadmium and lead are found widely in the environment and they have important biological functions. Lead (Pb) and cadmium (Cd) can accumulate in the lungs, liver, bone, and kidneys and cause serious organ damage. In the present study, we investigated the effect of AdM, Pb + AdM, and Cd + AdM treatments on superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as the level of malondialdehyde (MDA) in the kidney. Heavy metal accumulation was determined in kidney with and without AdM infusion and kidney damage was evaluated by light and electron microscopy. Increased heavy metal accumulation was observed in the heavy metal and AdM treated groups. SOD, CAT, GSH-Px activities, and MDA levels were significantly different in the treatment groups when compared with the control group. Tubular degeneration, necrosis, cell swelling, mononuclear cell infiltration, and degenerated organelles were observed in the kidney following treatment. Therefore, AdM infusion has no beneficial and/or compensatory role in cadmium and lead toxicity in the kidney. We conclude that heavy metal accumulation in the kidney in conjunction with AdM infusion is cytotoxic despite the known beneficial effects of adrenomedullin.
authors.affiliation: Department of Molecular Biology, Inonu University, Malatya 44280, Turkey. myurekli@inonu.edu.tr
authors.forename: Muhittin
authors.initials: M
authors.lastname: Yurekli
authors.forename: M
authors.initials: M
authors.lastname: Esrefoglu
authors.forename: M
authors.initials: M
authors.lastname: Ilker Doğru
authors.forename: Arzu
authors.initials: A
authors.lastname: Doğru
authors.forename: M
authors.initials: M
authors.lastname: Gul
authors.forename: M
authors.initials: M
authors.lastname: Whidden
mesh_terms: D053607:Adrenomedullin / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007854:Lead / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002104:Cadmium; D053607:Adrenomedullin; D007854:Lead; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase