Effects of captopril on the development of rat doxorubicin nephropathy.
The effects of a daily administration of an anti-converting enzyme inhibitor. Captopril (CPT) (100 mg/kg/orally), on the development of functional and morphological alterations induced in rats by a single injection (7.5 mg/kg/iv) of Doxorubicin (DXR) (Adriamycin*), were investigated. Twenty-four-hour protein excretion, urine output, food intake, water intake, and body weight gain were measured weekly for 30 days. Transmission and scanning electron microscopy observations were performed on kidney samples after 30 days. Four groups were studied. Group 1 were control rats. Group 2 were rats injected with DXR. Group 3 were rats injected with DXR and treated with CPT for 30 days. Group 4 were rats injected with DXR and treated with CPT for 15 days (CPT treatment started 15 days after DXR injection). Group 1 did not show significant functional or morphological changes. Group 2 showed severe proteinuria, significant increase in urinary volume within 2 weeks, significant body weight reduction and diffuse morphological changes. These changes mainly consisted of podocyte swelling, severe foot process fusion, and presence of casts within tubular lumen. Group 3, with respect to group 2, showed a significant reduction of the 24 h protein excretion and urine output. This group displayed morphological changes similar to those observed in group 2, but with a focal distribution. Group 4 showed functional and morphological changes comparable with those of group 2. It is concluded that CPT partially inhibits the development of the functional and morphological damage induced by DXR in the rat kidney. However, CPT did not influence the natural development of nephropathy when treatment started 15 days after DXR injection.
Squadrito
F
F
Institute of Pharmacology, Medical School, University of Messina, Italy.
Macchiarelli
G
G
Santoro
G
G
Arcoraci
V
V
Trimarchi
G R
GR
Sturniolo
R
R
Nottola
S A
SA
Motta
P M
PM
Caputi
A P
AP
D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D009393:Nephritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D004317:Doxorubicin; D002216:Captopril