Protein-rich diet attenuates cyclosporin A-induced renal tubular damage in rats.
OBJECTIVE
The objective of the present study was to look at the effect of a protein-rich diet on cyclosporine A (CsA)-induced acute nephrotoxicity in rodents using markers of tubular damage.


METHODS
Female Sprague-Dawley rats were conditioned to either a standard or a casein-rich diet for 2 weeks. Then, they were given CsA intraperitoneally (25 mg/kg/24 h or an equivalent volume of vehicle (Cremophor EL; Sigma Chemical Co, St. Louis, MO) for 7 days at 7 AM.


RESULTS
During CsA treatment, bodyweight, caloric consumption, water intake, and urine output were not significantly different in animals fed with the standard Rat Chow and those on the high-protein feeding. On days 1 and 7, the 24-hour urine excretion of N-acetyl-beta-d-glucosaminidase (NAG) and beta-galactosidase (beta-GAL) were significantly (P < .001) lower in CsA-treated rats on the high-protein diet than in those on the standard Rat Chow. After 7 days of treatment with CsA, no significant difference in the renal function level was found between rats fed with the standard or the casein-rich diet. The post-necrotic cellular regeneration in renal cortex was significantly lower (p<0.001) in CsA-treated rats on the high-protein than on the standard diet. In CsA-treated rats on the standard diet, immunogold labeling showed a massive and specific concentration of the drug into lysosomes of proximal tubular cells. Contrastingly, no gold particle was found over the lysosomes of animals given the rich-protein feeding.


CONCLUSIONS
In our current experimental conditions, a protective effect of high-casein diet against CsA-induced proximal tubular damage was observed in Sprague-Dawley rats.
Pons
Marianne
M
Centre de Recherche en Infectiologie du Centre Hospitalier Universitaire de Québec, Pavillon, Canada.
Plante
Isabelle
I
LeBrun
Michel
M
Gourde
Pierrette
P
Simard
Marie
M
Grenier
Louis
L
Thibault
Louise
L
Labrecque
Gaston
G
Beauchamp
Denis
D
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D001835:Body Weight; D002364:Caseins / Q000008:administration & dosage; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects* / Q000032:analysis; D018752:Diet, Fat-Restricted; D004044:Dietary Proteins / Q000008:administration & dosage*; D004231:Diuresis; D004326:Drinking; D002149:Energy Intake; D005260:Female; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D001616:beta-Galactosidase / Q000652:urine; D005723:gamma-Glutamyltransferase / Q000652:urine
D002364:Caseins; D004044:Dietary Proteins; D016572:Cyclosporine; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D001616:beta-Galactosidase; D000118:Acetylglucosaminidase