Cold exposure can induce a form of environmental stress. Cold stress (CS) alters homeostasis, results in the creation of reactive oxygen species and leads to alterations in the antioxidant defense system. The caffeic acid phenethyl ester (CAPE), an active component of propolis, has an antioxidant capacity. We investigated the effect of CS on oxidative stress and antioxidant defense system and the possible protective effect of CAPE in rat liver tissue. Twenty-four female Wistar Albino rats were divided into four groups: Control, CAPE-treated, CS, and CAPE-treated CS (CS + CAPE) group. Catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activities and total glutathione (GSH) and malondialdehyde (MDA) levels were measured. In addition, histological changes in liver tissue were examined by light microscopy. SOD, CAT and GSH-Px activities and total GSH level were significantly declined in the CS group. In the CS + CAPE group, the activities of these three enzymes and GSH level significantly raised with regard to the CS group. MDA levels increased in the CS group and decreased in the CS + CAPE group. The tissues of the CS group showed some histopathological changes such as necrosis, hepatocyte degeneration, sinusoidal dilatation, hemorrhage and vascular congestion and dilatation. In the CS + CAPE group, the histopathological evidence of hepatic damage was markedly reduced. Histological parameters were consistent with biochemical parameters. In this study, CS increased oxidative stress in liver tissue. CAPE regulated antioxidant enzymes, inhibited lipid peroxidation and reduced hepatic damage.

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Adrenomedullin (AdM) was originally discovered as a vasorelaxant peptide. The antioxidative properties of AdM have been reported recently. Through its antioxidative effect, adrenomedullin can protect organs from damage induced by stressors. Lead, commonly detected in air, soil, water and food, is a major source of oxidative stress. The effect of AdM in the liver of rats exposed to lead was investigated. Twenty-four female Wistar rats were divided into four groups: a control group (C), adrenomedullin group (AdM), lead (Pb) group and lead + adrenomedullin (Pb + AdM) group. In the Pb-treated groups, the animals were exposed to lead in drinking water containing 250 ppm PbCl2 for 4 weeks. In the AdM-treated group, the animals received an i.p. injection of AdM (3000 ng kg(-1) body weight) in the third week of lead treatment for 1 week. The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were determined in the liver of rats. Histological changes in the liver were examined by light and electron microscopy as well. The MDA levels were increased significantly in the Pb-treated groups, but in the Pb + AdM group the MDA levels were decreased significantly when compared with the Pb group. AdM reduced hepatic damage in the Pb + AdM group, but the difference in the total histopathological scores between the Pb and Pb + AdM groups was not significant. When the results are taken together, it can be concluded that AdM may have protective or compensating effects in lead toxicity.

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.

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