Advanced Oxidation Protein Products Accelerate Renal Fibrosis in a Remnant Kidney Model

Abstract

Accumulation of plasma advanced oxidation protein products (AOPP) has been found in patients with chronic kidney disease. However, the biologic consequences of AOPP consumption on progression of renal disease still are unclear. For testing of the hypothesis that AOPP accelerate progression of chronic kidney disease, Sprague-Dawley rats were subjected to five-sixths nephrectomy (5/6 Nx) or to sham operation. Rats in each group were randomly assigned in three subgroups (n ‫؍‬ 30 in each group) and treated with repeated intravenous injections of AOPP-modified rat serum albumin (RSA), unmodified RSA, or vehicle for indicated period. Compared with RSA-or vehicle-treated 5/6 Nx rats, AOPP RSA-treated 5/6 Nx rats displayed greater proteinuria, higher serum creatinine, and lower creatinine clearance. AOPP challenge resulted in more renal hypertrophy, higher macrophage influx, and greater renal fibrosis in the remnant kidney. Chronic administration of AOPP in sham-operated rats increased urinary protein excretion and renal macrophage infiltration, but histologic renal fibrosis was not observed during the study period. AOPP treatment enhanced AOPP level in renal tissue. This was associated with marked increase of thiobarbituric acid reactive substances, decrease of glutathione peroxidase activity, and upregulated expression of monocyte chemoattractant protein-1 and TGF-␤1 in renal cortex. These data indicate that AOPP might be a new and potentially important mediator of renal fibrosis in the remnant kidney. Chronic accumulation of AOPP promotes renal fibrosis probably via a redox-sensitive inflammatory pathway.

Protective effect of baicalein on renal ischemia/reperfusion injury in the rat

“…16 It has been reported that in patients with chronic kidney disease, AOPPs act on redox-sensitive inflammatory pathways to promote renal fibrosis and accelerate disease progression. 17 In AKI such as that after coronary artery bypass graft surgery, AOPPs can be used as prognostic biomarkers to measure the recovery progress. 18 Additionally, ROS not only elicit injury to reperfused tissue directly, they also amplify the effect of injury of ROS through peroxidation (oxidative stress).…”

Ethanol extraction of Picrorhiza scrophulariiflora prevents renal injury in experimental diabetes via anti-inflammation action

“…The creatinine clearance rate (Ccr) was calculated as described and factored for body weight (Li et al 2007a). 24 hr UAE was measured using the Coomassie Blue method (Lott et al 1983).…”

“…3!0 . 3 mm areas of the tubulointerstitium for each kidney (Li et al 2007a). The intensity of glomerular staining of TGFB1, CCL2, and fibronectin was evaluated at a 400!…”

“…The level of advanced oxidation protein products (AOPP) in renal tissue was measured as described previously (Li et al 2007a).…”

Advanced oxidation protein products from the follicular microenvironment and their role in infertile women with endometriosis

“…Due to the sensitivity, stability, convenience and cost of detection, the role of AOPPs in predicting the severity of oxidative stress and disease prognosis has become increasingly important. AOPPs may accelerate renal fibrosis and atherosclerosis, and may be detrimental to the progression of chronic kidney disease (22)(23)(24). In postmenopausal women, AOPPs are negatively associated with a reduced bone mineral density, which increases an individual's risk of developing osteoporosis (25).…”