Experimental model of lead nephropathy

Journal Article · Mon Jun 01 00:00:00 EDT 1992 · Environmental Research; (United States)

DOI:https://doi.org/10.1016/S0013-9351(05)80203-8· OSTI ID:7159299

Khalil-Manesh, F; Gonick, H C ^[1]; Cohen, A ^[2]; Bergamaschi, E; Mutti, A ^[3]

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1. Cedars-Sinai Medical Center, Los Angeles, CA (United States)
2. UCLA-Harbor General Hospital, Torrance, CA (United States)
3. Univ. of Parma (Italy)

Male Sprague-Dawley rats were exposed to high-dose (0.5%) lead acetate for periods ranging from 1 to 9 months; then lead exposure was discontinued, and animals were sacrificed after 12 months. Two additional groups of low-dose (0.01%) and high-dose (0.5%) rats were exposed to lead for 6 months, then lead was discontinued and the rats were treated with three 5-day courses of 0.5% DMSA (dimercaptosuccinic acid) over the next 6 months. Low-dose lead-treated rats showed no significant pathological changes with or without DMSA treatment, but exhibited a significant increase in GFR after DMSA. High-dose lead-treated animals showed no functional or pathological changes when lead exposure was discontinued after 1 month. However, when duration of exposure was 6 or 9 months, GFR was decreased and serum creatinine and urea nitrogen were increased as compared to controls. Tubulointerstitial disease was severe. Administration of DMSA resulted in an improvement in GFR and a decrease in albuminuria, together with a reduction in size and number of nuclear inclusion bodies in proximal tubules. However, tubulointerstitial scarring was only minimally reduced. It may be concluded that, except for brief initial exposure, discontinuation of high-dose lead exposure fails to reverse lead-induced renal damage. Treatment with the chelator, DMSA, improves renal function but has less effect on pathological alterations. As GFR improved after DMSA treatment in both low-dose and high-dose lead-treated rats, irrespective of the degree of pathological alterations, it may be concluded that the DMSA effect is most likely mediated by hemodynamic changes.

• OSTI ID: 7159299
• Journal Information: Environmental Research; (United States), Vol. 58:1, Issue 1-2; ISSN 0013-9351
• Country of Publication: United States
• Language: English

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