The modifier protein of glyceraldehyde-3-phosphate dehydrogenase reduces free radical-mediated renal damage in a rat model of acute kidney injury.
BACKGROUND
The modifier protein (MP) of glyceraldehyde-3-phosphate dehydrogenase has been shown to promote growth of renal epithelial cells in vitro. The aim of this study was to show the in vivo effects of MP in a rat model of gentamicin-induced acute kidney injury (AKI).


METHODS
MP was purified from monkey renal tubular epithelial cell line BSC-1 and confirmed by amino acid sequencing. Male Sprague-Dawley rats were divided into the following groups: normal control, gentamicin-treated, epidermal growth factor (EGF) plus gentamicin-treated, and MP plus gentamicin-treated, as well as control groups for EGF and MP alone. Levels of serum creatinine (SCr), serum and tissue lipid peroxide, nitric oxide and glutathione-S-hydrogenase for each group were measured on the 7th and 14th days of treatment. Tissue sections were studied with light microscopy.


RESULTS
The gentamicin-treated group showed a marked increase in SCr compared to the normal control group. Co-treatment of gentamicin with MP and/or EGF produced similar significant decreases preventing the increase in SCr. There were also significant reductions in serum and tissue homogenate levels of lipid peroxide and nitric oxide, accompanied by an increase in the level of glutathione-S-hydrogenase, in the MP co-treated groups compared to the gentamicin-treated group. AKI was confirmed histologically in the gentamicin-treated group, with damage to the tubular epithelium recorded. This was attenuated by MP co-treatment. There were also reductions in the expression of intercellular adhesion molecule-1 and proliferating cell nuclear antigen in the MP co-treated groups.


CONCLUSIONS
Using a gentamicin model of AKI, MP was able to reduce free radical production in kidney tissue and in the circulation, thus preventing oxidant injury and minimizing damage in renal epithelial cells.
Li
Zi-Long
ZL
Department of Nephrology, First Affiliated Hospital of China Medical University, Shenyang, China. lzl1017@yahoo.com
Sun
Ying-Hui
YH
Fan
Qiu-Ling
QL
Wang
Jun
J
Wang
Juan
J
Ren
Qing
Q
Liang
Zai-Fu
ZF
Ma
Jian-Fei
JF
Wang
Li-Ning
LN
D000208:Acute Disease; D000818:Animals; D002522:Chlorocebus aethiops; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D005609:Free Radicals; D005839:Gentamicins / Q000494:pharmacology; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007668:Kidney / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000473:pathology*; D015227:Lipid Peroxidation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D005609:Free Radicals; D005839:Gentamicins; D018799:Intercellular Adhesion Molecule-1; D003404:Creatinine; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)