title: Endogenous female sex hormones delay the development of renal dysfunction in apolipoprotein E-deficient mice.
abstract: BACKGROUND
  Hypercholesterolemia is a well-established risk factor for the development of kidney injury. Considering that female sex hormones may play a preventative role in both cardiovascular and renal diseases, the aim of the present study was to evaluate the effects of female sex hormones on hypercholesterolemia-induced renal dysfunction.
  
  
  METHODS
  Apolipoprotein E-deficient (ApoE) and C57 control female mice underwent an ovariectomy (OVX) or sham surgery and after 2 months, creatinine clearance, uremia and proteinuria were determined. Renal oxidative stress and lipid deposition were also quantified. Values are presented as mean ± SEM. Statistical analyses were performed using Two-way ANOVA followed by Tukey's post hoc test.
  
  
  RESULTS
  Creatinine clearance (μL/min) was similar between C57 (171 ± 17) and ApoE (140 ± 26) mice underwent sham surgery. OVX resulted in a reduced glomerular filtration rate in both C57 (112 ± 8, ~ - 35%, p < 0.05) and ApoE (61 ± 10, ~ - 56%, p < 0.05) animals. Plasma levels of urea (mg/dL) were higher in both ApoE groups (Sham: 73 ± 7; OVX: 73 ± 8, p < 0.05) when compared to C57 animals (Sham: 49 ± 3; OVX: 60 ± 4), with no changes among ovariectomized groups. Proteinuria levels (mg/24 h) were similar between C57 (Sham: 25.1 ± 5.7; OVX: 33.7 ± 4.7) and ApoE sham animals (26.4 ± 3.5), however, 24-h urine protein excretion was augmented in ApoE OVX animals (49.6 ± 5.8, p < 0.05). Histological kidney analysis demonstrated that the absence of female sex hormones resulted in increased oxidative stress, which was more severe in ApoE mice (C57 Sham: 9.2 ± 0.4; C57 OVX: 22.9 ± 1.0; ApoE Sham: 13.9 ± 0.7; ApoE OVX: 34.0 ± 1.4 au x 103, p < 0.05). As expected, ApoE mice presented higher lipid deposition, which was not affected by OVX (C57 Sham: 0 ± 0; C57 OVX: 0 ± 0; ApoE Sham: 6.8 ± 1.6; ApoE OVX: 5.2 ± 0.8% x 10-2, p < 0.05). Ovariectomy resulted in a similar reduction in ER-α protein expression in the renal cortex (C57: 0.78 ± 0.04; ApoE: 0.81 ± 0.04 au, p < 0.05) when compared to sham animals (C57:1.00 ± 0.04; ApoE: 1.03 ± 0.03 au).
  
  
  CONCLUSIONS
  Taken together these data indicate that female sex hormones may delay hypercholesterolemia-induced renal dysfunction and emphasizes the importance of plasma cholesterol control in post-menopausal women.
authors.forename: Sonila S
authors.initials: SS
authors.lastname: Carneiro
authors.forename: Raffaela Z
authors.initials: RZ
authors.lastname: Carminati
authors.forename: Flavia P S
authors.initials: FP
authors.lastname: Freitas
authors.forename: Priscila L
authors.initials: PL
authors.lastname: Podratz
authors.forename: Camille M
authors.initials: CM
authors.lastname: Balarini
authors.affiliation: Laboratory of Translational Physiology, Physiological Sciences Graduate Program, Health Sciences Center, Federal University of Espirito Santo, Av Marechal Campos 1468, 29042-755 Vitoria, ES, Brazil. jbgraceli@gmail.com.
authors.forename: Jones B
authors.initials: JB
authors.lastname: Graceli
authors.forename: Silvana S
authors.initials: SS
authors.lastname: Meyrelles
authors.forename: Elisardo C
authors.initials: EC
authors.lastname: Vasquez
authors.forename: Agata L
authors.initials: AL
authors.lastname: Gava
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006937:Hypercholesterolemia / Q000209:etiology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D047628:Estrogen Receptor alpha; D004967:Estrogens; D013481:Superoxides