Experimental model of lead nephropathy. I. Continuous high-dose lead administration

Abstract

This study followed the progression of lead nephropathy in male Sprague-Dawley rats (E) administered lead acetate (0.5%) continuously in drinking water for periods ranging from 1 to 12 months. Control animals (C) were pair-fed. Observations included renal pathology by light and electron microscopy, wet and dry kidney weights, and glomerular filtration rate (GFR) to assess renal function. Urinary excretion of lead, the enzymes N-acetyl-beta-D-glucosaminidase (NAG) and glutathione-S-transferase (GST), and brush border antigens (BB50, CG9, and HF5) were utilized to explore possible markers of kidney injury. GFR was increased significantly after three months of lead exposure, but was decreased significantly after 12 months. Kidney wet weights were significantly greater in E than C from three months on. Kidney dry weight/wet weight ratio was constant up to three months, but decreased in E at 12 months. Glomerular diameters were normal at all time periods; the nephromegaly was related primarily to hypertrophy of proximal tubules. Lead inclusion bodies were found in nuclei of proximal convoluted tubules and pars recta at all times. Tubular atrophy and interstitial fibrosis first appeared at six months, and increased in severity thereafter. Brush borders of proximal tubules were disrupted at one and three months, but recovered thereafter. Focal and segmental glomerulosclerosis was observed in 2 of 10 rats at 12 months. Arteries and arterioles remained normal at all time periods. Urinary NAG was elevated in E above C after three months of lead exposure. However, urinary NAG in C also increased with age, obscuring changes in the 12 month E rats. GST was elevated after three months of lead administration in E, not without an attendant age-related increase in C rats. In three-month E rats, urinary brush border antigens were increased above C, but were decreased at six and 12 months, correlating with the morphologic changes in brush border. We conclude that a high dose of lead in rats may initially stimulate both renal cortical hypertrophy and an increase in GFR. Later, the adverse effects of lead on the tubulointerstitium predominate, and GFR falls. The urinary marker, NAG, was abnormal in the early stages of the disease, but age-related changes obscured its utility at later stages; urinary GST appeared to be a more consistent marker of injury.

Activities of Antioxidant and Detoxifying Enzymes in Rats after Lead Exposure

“…furthermore, lead can induce pathological changes in the structure and function of this organ (Khalil-Manesh et al 1992). The results of research on the lead influence on the soD activity are divergent.…”

Heavy metal concentrations in female wild mink (Neovison vison) in Sweden: Sources of variation and associations with internal organ weights

“…A common finding in experimental studies on rats is that Pb seems to cause an increase in kidney weight [43][44][45][46][47]; however, there are also some studies reporting no effect on kidney …”

Lead Acetate Effects on Hepatocyte Degeneration in Chick Embryo Liver

“…[16] High levels of lead accumulate in tissues where lead-induced pathological changes occur in their structure and function. [17] Specifically, lead is known to cause impairment of liver functions and kidney dysfunction as well. [18] The present study supports that lead acetate treated chick embryo liver showed significant toxic changes which are manifested as hepatic damage ( Figure: 2&3).…”