title: Tibolone has anti-inflammatory effects in estrogen-deficient female rats on the natriuretic peptide system and TNF-alpha.
abstract: Cardiovascular and immune system abnormalities have been reported in females with estrogen deficiency. To control these disorders in post-menopausal women, hormone replacement therapy (HRT) has been used. Tibolone has been used as a HRT, but the effects of tibolone on the natriuretic peptide system have not been determined. We investigated the effects of tibolone on the natriuretic peptide system and pro-inflammatory cytokines in ovariectomized (OVX) rats. Female rats were divided into four groups: SHAM, OVX, OVX treated with 17β-estradiol (OVX+E: 14 days) and OVX treated with tibolone (OVX+T: 14 days) beginning 21 days after ovariectomy. On day 35, blood was collected to determine atrial natriuretic peptide (ANP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. In addition, tissues were collected for determining ANP, natriuretic peptide receptor type-A (NPR-A), and NPR type-C (NPR-C) gene expression levels by RT-PCR. The cytokine levels of both IL-6 and TNF-α were increased in OVX animals. In comparison, IL-6 and TNF-α levels were reduced in OVX+E animals. TNF-α levels were reduced similarly in OVX+T animals, but IL-6 levels remained elevated in this group. The concentrations of ANP in the left atrium tissue and plasma were decreased after ovariectomy, as were ANP mRNA levels in the left atrium and NPR-A mRNA levels in kidney. No variation in NPR-C gene expression in the kidney tissue was observed among the groups. Tibolone and 17β-estradiol effectively increased plasma ANP and ANP mRNA levels in the left atrium, but did not normalize renal NPR-A levels. Since HRT with tibolone normalizes plasma ANP and serum TNF-alpha levels our results suggest that treatment with tibolone has anti-inflammatory effects and could prevent cardiovascular disease in the long-term.
authors.affiliation: Biological and Health Sciences, Federal Institute of Espírito Santo, Vila Velha, ES, Brazil.
authors.forename: Ana Raquel Santos
authors.initials: AR
authors.lastname: de Medeiros
authors.forename: Aline Zandonadi
authors.initials: AZ
authors.lastname: Lamas
authors.forename: Izabela Facco
authors.initials: IF
authors.lastname: Caliman
authors.forename: Polyana L Meireles
authors.initials: PL
authors.lastname: Dalpiaz
authors.forename: Luciana Barbosa
authors.initials: LB
authors.lastname: Firmes
authors.forename: Gláucia Rodrigues
authors.initials: GR
authors.lastname: de Abreu
authors.forename: Margareth Ribeiro
authors.initials: MR
authors.lastname: Moysés
authors.forename: Elenice Moreira
authors.initials: EM
authors.lastname: Lemos
authors.forename: Adelina Martha
authors.initials: AM
authors.lastname: dos Reis
authors.forename: Nazaré Souza
authors.initials: NS
authors.lastname: Bissoli
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology; D006339:Heart Rate / Q000187:drug effects; D020249:Hormone Replacement Therapy / Q000379:methods*; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000378:metabolism; D009652:Norpregnenes / Q000627:therapeutic use*; D009929:Organ Size; D010052:Ovariectomy / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D004967:Estrogens; D015850:Interleukin-6; D009652:Norpregnenes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C; C027385:tibolone