title: Aging and the disposition and toxicity of mercury in rats.
abstract: Progressive loss of functioning nephrons, secondary to age-related glomerular disease, can impair the ability of the kidneys to effectively clear metabolic wastes and toxicants from blood. Additionally, as renal mass is diminished, cellular hypertrophy occurs in functional nephrons that remain. We hypothesize that these nephrons are exposed to greater levels of nephrotoxicants, such as inorganic mercury (Hg(2+)), and thus are at an increased risk of becoming intoxicated by these compounds. The purpose of the present study was to characterize the effects of aging on the disposition and renal toxicity of Hg(2+) in young adult and aged Wistar rats. Paired groups of animals were injected (i.v.) with either a 0.5μmol·kg(-1) non-nephrotoxic or a 2.5μmol·kg(-1) nephrotoxic dose of mercuric chloride (HgCl2). Plasma creatinine and renal biomarkers of proximal tubular injury were greater in both groups of aged rats than in the corresponding groups of young adult rats. Histologically, evidence of glomerular sclerosis, tubular atrophy, interstitial inflammation and fibrosis were significant features of kidneys from aged animals. In addition, proximal tubular necrosis, especially along the straight segments in the inner cortex and outer stripe of the outer medulla was a prominent feature in the renal sections from both aged and young rats treated with the nephrotoxic dose of HgCl2. Our findings indicate 1) that overall renal function is significantly impaired in aged rats, resulting in chronic renal insufficiency and 2) the disposition of HgCl2 in aging rats is significantly altered compared to that of young rats.
authors.affiliation: Mercer University School of Medicine, Division of Basic Medical Sciences, Macon, GA 31207, United States. Electronic address: bridges_cc@mercer.edu.
authors.forename: Christy C
authors.initials: CC
authors.lastname: Bridges
authors.affiliation: Mercer University School of Medicine, Division of Basic Medical Sciences, Macon, GA 31207, United States.
authors.forename: Lucy
authors.initials: L
authors.lastname: Joshee
authors.affiliation: Mercer University School of Medicine, Division of Basic Medical Sciences, Macon, GA 31207, United States.
authors.forename: Rudolfs K
authors.initials: RK
authors.lastname: Zalups
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D008627:Mercuric Chloride; D003404:Creatinine
keywords: Aging; Kidney; Mercury; Nephrotoxicant; Toxicology