High glucose can induce lipid peroxidation in the isolated rat glomeruli.
The present study examined the effect of elevated glucose on glomerular cell membrane lipid peroxidation. Glomeruli were isolated from male Sprague-Dawley rat kidneys utilizing a standard sieving method and incubated in medium containing different concentrations of glucose at 37 degrees C for one and 48 hours. The levels of lipid peroxides (LPO) in the glomeruli were quantitated by malondialdehyde-thiobarbituric acid adduct formation. The levels of LPO in the glomeruli were significantly increased after one hour of exposure to high glucose (HG; 30 mM) medium, and this increase was sustained after 48 hours of exposure to HG. In contrast, osmotic control media containing either L-glucose or mannitol did not increase glomerular LPO. Dimethylthiourea (20 mM), a hydroxyl radical scavenger, completely blocked the increase of LPO in the glomeruli exposed to HG not only for one hour but also for 48 hours without altering LPO levels in the glomeruli exposed to control glucose. This provides evidence that oxidative stress can be induced by high ambient concentrations of glucose. Pretreatment with PKC antagonists, either 500 microM H-7 or 100 nM staurosporine, prevented the increase of LPO in the glomeruli exposed to HG for one hour but not in glomeruli exposed for 48 hours. These data suggest that (i) elevated glucose levels per se can cause oxidative stress and augment membrane lipid peroxidation of glomeruli, and (ii) activation of PKC may play a role in early phase of glucose-induced glomerular lipid peroxidation.
Ha
H
H
Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
Yoon
S J
SJ
Kim
K H
KH
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine
D000470:Alkaloids; D007546:Isoquinolines; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; D005947:Glucose