Effect of captopril on doxorubicin-induced nephrotoxicity in normal rats

Pharmacol Res. 1999 Mar;39(3):233-7. doi: 10.1006/phrs.1998.0432.

Abstract

Biochemical evaluations of the effects of the sulfhydryl-containing angiotensin-converting enzyme inhibitor (captopril) on the nephrotoxicity induced by doxorubicin in normal rats were carried out. A single dose of doxorubicin (15 mg kg-1) which caused nephrotoxicity was manifested biochemically by the elevation of serum urea after 24 and 48 h of administration. Also a severe decrease in total proteins and albumin after 4, 24 and 48 h was observed. Moreover, a decrease of non-protein sulfhydryl (-SH) concentrations in the kidney tissues after 24 h and an increase in the lipid peroxidation was observed after 4 h administration of doxorubicin. Captopril (60 mg kg-1 i.p.) injection did not induce any change in the biochemical parameters measured, however, captopril administered 1 h before doxorubicin ameliorated the biochemical toxicity induced by doxorubicin. This was evidenced by a significant reduction in serum urea and the lipid peroxidation after 4 and 24 h and a significant reduction in creatinine after 48 h. Also, the captopril amelioration was evidenced by an increase in total proteins and albumin after 4 and 24 h of doxorubicin administration. Captopril did not change non-protein sulfhydryl (-SH) concentrations or protein content in the kidney tissues. These results suggest that captopril may be beneficial as a protective agent against nephrotoxicity induced by doxorubicin.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Blood Proteins / metabolism
  • Calcium / blood
  • Captopril / pharmacology*
  • Creatinine / blood
  • Doxorubicin / antagonists & inhibitors
  • Doxorubicin / toxicity*
  • Female
  • Free Radical Scavengers
  • Kidney Diseases / chemically induced
  • Kidney Diseases / prevention & control*
  • Lipid Peroxides / metabolism
  • Male
  • Potassium / blood
  • Protective Agents / pharmacology
  • Rats
  • Serum Albumin / metabolism
  • Sodium / blood
  • Sulfhydryl Compounds / metabolism
  • Urea / blood

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antibiotics, Antineoplastic
  • Blood Proteins
  • Free Radical Scavengers
  • Lipid Peroxides
  • Protective Agents
  • Serum Albumin
  • Sulfhydryl Compounds
  • Doxorubicin
  • Urea
  • Captopril
  • Sodium
  • Creatinine
  • Potassium
  • Calcium