Glucocorticoid activates glomerular antioxidant enzymes and protects glomeruli from oxidant injuries

Abstract

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.

Oxidants in Chronic Kidney Disease

“…• induction of antioxidant enzymes by ischemia-reperfusion injury protects against H 2 O 2 -induced proteinuria (126) • induction of antioxidant enzymes by glucocorticoids protects against PAN-induced proteinuria (127) Evidence for the role of oxidants in passive Heymann nephritis…”

Identification of Proteins Binding to E-Box/Ku86 Sites and Function of the Tumor Suppressor SAFB1 in Transcriptional Regulation of the Human Xanthine Oxidoreductase Gene

“…In acute renal failure, endotoxin-induced mucosal injury, viral pneumonia, ischemia-reperfusion injury, and cutaneous photosensitivity to hematoporphyrins, excess XOR-derived ROS have been demonstrated to cause tissue injury (15)(16)(17)(18)(19)(20)(21)(22). In addition, XOR activity and gene expression are induced by LPS, cytokines, and hypoxia and during ischemia/reperfusion (23)(24)(25)(26)(27).…”

“…Importantly, a central role for XOR also has been demonstrated in a variety of clinical disorders and relevant animal models associated with oxidative stress or injury, including inflammation, infection, ischemic tissue injury, and various cancers (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). In acute renal failure, endotoxin-induced mucosal injury, viral pneumonia, ischemia-reperfusion injury, and cutaneous photosensitivity to hematoporphyrins, excess XOR-derived ROS have been demonstrated to cause tissue injury (15)(16)(17)(18)(19)(20)(21)(22).…”

Effect of Methylprednisolone on Plasma Lipid Peroxidation Induced by Lipopolysaccharide

“…Kawamura et al (13) indicat ed that glucocorticoids enhanced the endogenous activity of glomerular antioxidant enzymes, instances of renal injury caused by reactive oxygen species and attenuated lipid peroxidation.…”