Tubular Injury and Regeneration in the Rat Kidney Following Acute Exposure to Gentamicin: A Time-Course Study
| Autor: | R P Schaudies, Guy Laurent, S Wrona, Jacqueline Zanen, Jeanine-Anne Heuson-Stiennon, Gérard Toubeau, Denis Nonclercq |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
medicine.medical_specialty
Pathology Time Factors Renal cortex Immunocytochemistry Critical Care and Intensive Care Medicine S Phase Nephrotoxicity Rats Sprague-Dawley Internal medicine medicine Animals Regeneration Phospholipidosis Kidney Epidermal Growth Factor business.industry Regeneration (biology) Aminoglycoside General Medicine Kidney Tubular Necrosis Acute Hyperplasia medicine.disease Immunohistochemistry Rats Kidney Tubules medicine.anatomical_structure Endocrinology Nephrology Female Gentamicins Lysosomes business |
| Zdroj: | Renal Failure. 14:507-521 |
| ISSN: | 1525-6049 0886-022X |
| DOI: | 10.3109/08860229209047660 |
| Popis: | Aminoglycoside antibiotics act as nephrotoxic drugs, inducing a lysosomal phospholipidosis and necrotic lesions essentially in convoluted proximal tubules. Previous studies have demonstrated that tubular injury caused by these compounds elicits a process of renal tissue repair (tubular regeneration) involving an increase of cell turnover in tubular epithelium. The present study was performed in order to: (i) achieve further insight into the temporal relationship between aminoglycoside-induced phospholipidosis, tubular necrosis, and tubular regeneration; and (ii) approach the control of tubular regeneration after nephrotoxin-induced insult. To investigate the latter point, we examined by immunocytochemistry the intrarenal distribution of epidermal growth factor (EGF) during tubular regeneration. Five groups of female Sprague-Dawley rats (n = 5) were treated for 4 days with gentamicin i.p. at a daily dose of 50 mg/kg delivered in 2 injections per day. Sham-treated animals (n = 5) received an equivalent amount of vehicle (0.9% NaCl) according to the same protocol. Groups of treated rats, and controls, were terminated 16 h (day 1), 4 days, 7 days, 14 days, and 21 days after the end of gentamicin administration. One hour prior to necropsy, each animal was given an i.p. injection of 40 mg 5-bromo-2'-deoxyuridine (BrdU) for the immunocytochemical demonstration of S-phase cells, using an anti-BrdU monoclonal antibody. Renal tissue was processed for light microscopy analysis, namely: a computer-aided morphometry of lysosomes in proximal tubular cells, a single-blind evaluation of gentamicin-induced tubular injury, the measurement of cell proliferation by immunocytochemical detection of BrdU-labeled nuclei, the demonstration of EGF-like immunoreactive material in renal tissue by using anti-rat EGF antiserum and immunogold-silver staining. As revealed by the morphometry of lysosomes in proximal tubular epithelium, the degree of gentamicin-induced phospholipidosis was maximum at day 1 (relative area occupied by lysosomes was increased 25-fold over mean control value) and declined thereafter. In contrast, tubular necrosis reached a peak 4 days after the end of drug administration. In proximal tubular epithelium, the stimulation of cell turnover associated with tubular regeneration showed a peak at day 7 (15-fold the mean control value). Tubular regeneration was also accompanied by mild interstitial hyperplasia. Three weeks after treatment with gentamicin, morphological evidence of drug-induced injury had disappeared due to the tissue repair process, except for the occasional presence of small hyperplastic foci in renal cortex interstitium. In both treated animals and controls, EGF immunoreactivity as revealed by immunocytochemical staining was associated with distal tubules (renal cortex and outer medulla).(ABSTRACT TRUNCATED AT 400 WORDS) |
| Databáze: | OpenAIRE |
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