Glucocorticoid activates glomerular antioxidant enzymes and protects glomeruli from oxidant injuries.
We examined the effect of glucocorticoid on intrinsic glomerular antioxidant enzyme (AOE) activities. Munich-Wistar rats were treated with daily i.p. injection of vehicle or methylprednisolone [MP, 15 mg/kg body wt, (MP15)] either for three days or nine days. Glomeruli isolated from rats given MP15 had significantly higher activities of total (T-) and manganese (Mn-) superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase than vehicle-treated rats (P less than 0.05). MP15-treated rats were subjected to intrarenal arterial infusion of hydrogen peroxide (35 mumol over 1 hr). Values for urinary protein excretion rate (UprV) after hydrogen peroxide infusion were markedly lower in rats pretreated with MP15 for both three days and nine days than in untreated rats (109 +/- 18 and 55 +/- 24 vs. 416 +/- 73 micrograms/min, respectively, both P less than 0.005). To test whether the same therapeutic intervention attenuates reactive oxygen species (ROS)-mediated glomerular injury in another model, rats given a single i.v. dose of puromycin aminonucleoside (PAN) (50 mg/kg body wt) were treated with daily i.p. injection of vehicle or MP15. Two days after PAN administration, when compared to vehicle-treated controls, PAN rats given MP15 had significantly higher activities of Mn-SOD, GSH-Px and catalase. After eight days of PAN injection, T- and Mn-SOD activities were, likewise, significantly higher in MP15- than vehicle-treated PAN rats. PAN rats given MP15 also had substantially less proteinuria, compared to PAN rats given vehicle alone, UprV averaging 32.3 +/- 9.4 versus 159.0 +/- 13.8 mg/24 hr (P less than 0.05). Elevated glomerular malondialdehyde (MDA) level characteristic of PAN rats was absent in rats treated with MP15. Moreover, epithelial foot process fusion and cell vacuolization seen in vehicle-treated PAN rats were markedly attenuated in MP15-treated PAN rats. These data indicate that the mechanism for therapeutic effect of glucocorticoids on ROS-mediated renal injuries includes an enhancement of endogenous glomerular AOE activities, which attenuates lipid peroxidation of glomerular tissue.
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
T
T
Kawamura
T
T
Yoshioka
T
T
Bills
A
A
Fogo
I
I
Ichikawa
D000818:Animals; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008775:Methylprednisolone / Q000494:pharmacology*; D011507:Proteinuria / Q000139:chemically induced / Q000517:prevention & control; D011692:Puromycin Aminonucleoside / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism
D008315:Malondialdehyde; D011692:Puromycin Aminonucleoside; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D008775:Methylprednisolone