title: Oxidant stress in hyperlipidemia-induced renal damage.
abstract: Hyperlipoproteinemia can aggravate glomerulosclerosis and chronic tubulointerstitial (ti) damage in kidneys without primary immunologic disease. We evaluated whether the effect of hyperlipidemia on progression of renal damage differed between kidneys without preexisting glomerular disease and kidneys with mesangioproliferative glomerulonephritis and whether the renal actions of hyperlipidemia were dependent on oxidant-antioxidant balance. Hyperlipidemia was induced by high-fat and high-cholesterol diet in uninephrectomized rats. In rats without glomerulonephritis, hyperlipidemia led to a rise in glomerular and ti generation of reactive oxygen species (ROS). Oxygen radicals were mainly generated by enhanced xanthine oxidoreductase (XO), which rose with protein concentration and activity during hyperlipidemia; concurrently, glomerulosclerosis and chronic ti injury were noticed during hyperlipidemia [ti damage (% of total tubulointerstitium (TI) after 150 days): normolipidemia 0.1 +/- 0% vs. hyperlipidemia 3.4 +/- 0. 9%; P < 0.05]. In mesangioproliferative Thy-1 nephritis, ti injury was significantly accelerated by hyperlipidemia (ti damage after 150 days: normolipidemic Thy-1 nephritis 2.5 +/- 0.6% vs. hyperlipidemic Thy-1 nephritis 12.5 +/- 3.1%; P < 0.05). Antioxidant enzyme activities decreased and XO activity rose markedly in the TI (XO activity in TI after 150 days: normolipidemic Thy-1 nephritis 2.2 +/- 0.5 vs. hyperlipidemic Thy-1 nephritis 4.5 +/- 0.7 cpm/microg protein; P < 0.05). In hyperlipidemic Thy-1 nephritis rats, which had a higher urinary protein excretion than normolipidemic rats, hypochlorite-modified proteins, an indirect measure for enhanced myeloperoxidase activity, were detected in renal tissue and in urine, respectively. During hyperlipidemia, chronic damage increased in renal TI. Enhanced generation of ROS, rise in oxidant enzyme activity, and generation of hypochlorite-modified proteins in renal tissue and urine were noticed. These data suggest that oxidant stress contributed to the deleterious effects of hyperlipidemia on the renal TI.
authors.affiliation: Department of Pathology, German Cancer Research Center, Heidelberg Germany.
authors.forename: H
authors.initials: H
authors.lastname: Scheuer
authors.forename: W
authors.initials: W
authors.lastname: Gwinner
authors.forename: J
authors.initials: J
authors.lastname: Hohbach
authors.forename: E F
authors.initials: EF
authors.lastname: Gröne
authors.forename: R P
authors.initials: RP
authors.lastname: Brandes
authors.forename: E
authors.initials: E
authors.lastname: Malle
authors.forename: C J
authors.initials: CJ
authors.lastname: Olbricht
authors.forename: A K
authors.initials: AK
authors.lastname: Walli
authors.forename: H J
authors.initials: HJ
authors.lastname: Gröne
mesh_terms: D000818:Animals; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003893:Desmin / Q000032:analysis; D004041:Dietary Fats / Q000008:administration & dosage; D015432:Glomerulonephritis, Membranoproliferative / Q000150:complications; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology; D006949:Hyperlipidemias / Q000150:complications* / Q000652:urine; D007672:Kidney Cortex / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008163:Luminescent Measurements; D008297:Male; D009097:Multienzyme Complexes / Q000032:analysis; D009247:NADH, NADPH Oxidoreductases / Q000032:analysis; D019255:NADPH Oxidases / Q000032:analysis; D009392:Nephrectomy; D009395:Nephritis, Interstitial / Q000209:etiology* / Q000378:metabolism / Q000652:urine; D018384:Oxidative Stress; D011507:Proteinuria / Q000209:etiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D002791:Cholesterol, Dietary; D003893:Desmin; D004041:Dietary Fats; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D013482:Superoxide Dismutase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases