Influence of β-adrenergic antagonists on cell proliferation rates in the kidney of untreated and diethylnitrosamine-treated male F344 rats

Rosanna Cardani, Giovanni Ragnotti, Giuseppe Radaelli, Teresa Zavanella

Research output: Contribution to journalArticle

Abstract

Some nongenotoxic chemicals which cause kidney tumors have been shown to stimulate tubular cell proliferation. The aim of this study was to evaluate the effects of two β-adrenoreceptor blocking agents, propranolol and atenolol, on cell proliferation rates in the kidneys of male F344 rats. Immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and mitotic index have been examined in formalin-stored kidneys from F344 rats used in an initiation-promotion study of carcinogenesis. Cell proliferation rate was quantified in the proximal tubule epithelium. Non-initiated rats and rats initiated with a single dose of diethylnitrosamine (DEN, 200 mg/kg, i.p.) were continuously treated with propranolol (75-100 mg/kg) or atenolol (300 mg/kg) by gavage and were sacrificed after 2, 4, 8 or 21 months of experimentation. There were two control groups, one untreated (D0) and one given distilled water by gavage (D1). Control group D1 showed significantly lower cell proliferation rates than the D0 group. In non-initiated rats, propranolol had a weak enhancing effect on cell proliferation, most evident after 4 months, while atenolol had a clear enhancing effect most evident after 8 months of promoting regimen. Treatment with DEN alone resulted in a significant increase in cell proliferation rate as compared to group D1. In DEN-initiated rats given propranolol, there was a borderline significant increase in cell proliferation rates, compared to rats given DEN alone, after 8 months of promoting regimen. Atenolol had no effect. Because of the differences in body weight gain and food consumption observed among the various groups, it is suggested that the state of nutrition may have obscured the effects of β-blockers on cell proliferation rates. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)217-231
Number of pages15
JournalChemico-Biological Interactions
Volume118
Issue number3
DOIs
Publication statusPublished - Apr 15 1999

Keywords

  • β-Blockers
  • Carcinogenesis
  • Cell proliferation
  • F344 rats
  • Kidney

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Influence of β-adrenergic antagonists on cell proliferation rates in the kidney of untreated and diethylnitrosamine-treated male F344 rats'. Together they form a unique fingerprint.

  • Cite this