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.

Endothelial Relaxation Mechanisms and Oxidative Stress Are Restored by Atorvastatin Therapy in Ovariectomized Rats

“…Those treatments lasted 14 days. As previously described [ 35 ], the effects of ovariectomy and estrogen treatment were confirmed by measuring the body and uterine weights at the time of the experiment.…”

Astrocytes Mediate Protective Actions of Estrogenic Compounds after Traumatic Brain Injury

“…For instance, it has been shown that estrogenic compounds regulate oedema, extracellular glutamate levels, reactive astrogliosis and inflammatory response after brain trauma [14, 15]. Therefore, they may be useful molecules for the management of TBI [11]. In the next sections, we review the participation of astrocytes in the response of neural tissue to injury and their role in mediating neuroprotective actions of estrogenic compounds to improve neuronal survival and functional outcomes after TBI.…”

Effects of Atrial Natriuretic Peptide on p53 and Estrogen Receptor in Breast Cancer Cells

“…These effects may be mediated through NPR-A receptors or crosstalk between ERα and NPR-A receptors. 25 , 26 Treatment with ANP alone or with E 2 increased the expression of NPR-A in breast cancer cells and these effects were reduced with antiestrogen in combination with E 2 and ANP. Further studies are warranted to examine the molecular mechanism of NPR-A effects by hormone and antihormone in breast cancer cells.…”