Prevention of cyclosporine-induced nephrotoxicity with dietary glycine.
BACKGROUND
The nonessential amino acid glycine has been used previously to prevent hypoxic and ischemic injury to kidney tissue in vitro. Furthermore, it was recently shown that glycine prevents activation of macrophages and neutrophils in vitro. Because there is some evidence that the immunosuppressant cyclosporine causes nephrotoxicity through a hypoxia-reoxygenation mechanism that could involve infiltration and activation of macrophages and neutrophils, we hypothesized that dietary glycine could prevent this injury.


METHODS
Rats were fed a diet containing glycine (5%) or a control diet for 3 days before cyclosporine treatment. To produce nephrotoxicity, cyclosporine (25 mg/kg daily by gavage) was administered for 28 days while animals were maintained on glycine or control diets. Serum creatinine, urea, glomerular filtration rates, and kidney histology were evaluated in different treatment groups.


RESULTS
All rats gained weight; however, overall weight gain in the cyclosporine, glycine, and cyclosporine+glycine groups was significantly less by about 40% compared with the control group. Diet consumption was not statistically different between the groups. As expected, cyclosporine caused kidney damage in the rats fed control diet, reflected in significantly elevated serum urea and creatinine. In addition, cyclosporine treatment decreased glomerular filtration rate by nearly 70%, caused proximal tubular dilation and necrosis as well as increased macrophage and neutrophil infiltration into the kidney. Dietary glycine prevented or minimized kidney damage due to cyclosporine in all parameters studied nearly completely. Furthermore, feeding glycine for up to 1 month had no detrimental effect on kidney function.


CONCLUSIONS
Dietary glycine is a safe and effective treatment to reduce the nephrotoxicity of cyclosporine.
Thurman
R G
RG
Department of Pharmacology, The University of North Carolina at Chapel Hill, 27599-7365, USA.
Zhong
Z
Z
von Frankenberg
M
M
Stachlewitz
R F
RF
Bunzendahl
H
H
D000821:Animal Feed; D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D004032:Diet; D004435:Eating / Q000502:physiology; D005998:Glycine / Q000008:administration & dosage* / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007962:Leukocytes / Q000473:pathology; D008264:Macrophages / Q000166:cytology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000502:physiology
D016572:Cyclosporine; D005998:Glycine