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.

Protective Effects of Curcumin on Cadmium-Induced Renal Injury in Young and Aged Rats

“…The kidney is one of the most vulnerable organ against the toxic effects of Cd (15). Intoxication of Cd results in common transport defects of the proximal tubules (9,16,17). In the present study, Cd caused severe renal damage in both the aged and young groups.…”

“…The effects of Cd on various cell types include chromatin condensation and damage to cell membranes, including the mitochondrial cristae membrane, resulting in an increase in their permeability (6). Cd exposure results in the impairment of the antioxidant defense system in the kidney and liver (7)(8)(9). As a matter of fact, the kidney is the most sensitive organ against Cd.…”

The Protective Effect of Adrenomedullin on Renal Injury, in a Model of Abdominal Aorta Cross-Clamping

“…11 Yurekli et al also found that AM significantly decreased MDA levels in kidney tissue after damage in cadmium and lead exposed rats. 12 In this study, AM significantly decreased the renal tissue level of MDA, which indicates that it decreased the magnitude of oxidative stress and subsequently lipid peroxidation. SOD and CT are naturally occurring intracellular enzymes which play a critical role in the defense of cells against the toxic effects ROS products by their scavenging capacity.…”

Accumulation of methylglyoxal and d‐lactate in Pb‐induced nephrotoxicity in rats

“…In the present study, Pb did not alter any biochemical parameters but damaged the renal structure and reduced the weight in rats (Table and Figure ). This might be due to the different salts of Pb that were used (chloride vs. nitrate) (Yurekli et al ., ). Consistent with our results, the poisoning of Pb damaged the proximal tubular function, which induced histopathological lesions and disturbed the cell integrity (McLachlin, Goyer, & Cherian, ; Navarro‐Moreno et al ., ; Yurekli et al ., ; Martinez‐Alfaro et al ., ; Reddy, Chalamaiah, Ramesh, Balaji, & Indira, ).…”