Short-term administration of tibolone reduces inflammation and oxidative stress in the hippocampus of ovariectomized rats fed high-fat and high-fructose

ABSTRACT

Inflammation and oxidative stress are critical events involved in neurodegeneration. In animal models, it has been shown that chronic consumption of a hypercaloric diet, which leads to inflammatory processes, affects the hippocampus, a brain region fundamental for learning and memory processes. In addition, advanced age and menopause are risk factors for neurodegeneration. Hormone replacement therapy (HRT) ameliorates menopause symptoms. Tibolone (TB), a synthetic hormone, exerts estrogenic, progestogenic and androgenic effects on different tissues. We aimed to determine the effect of short-term TB administration on oxidative stress and inflammation markers in the hippocampus of ovariectomized rats fed a high-fat-and-fructose diet (HFFD). Adult female rats were ovariectomized (OVX) and fed standard diet or HFFD—consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water—and administered vehicle or TB (1 mg/kg for seven days). Finally, we administered hormone receptor antagonists (MPP, RU486 or FLU) to each of the OVX + HFFD + TB groups. Bodyweight, triglycerides and cholesterol, oxidative stress and inflammation markers, and the activity and expression of antioxidant enzymes were quantified in the hippocampus of each experimental group. We observed that short-term TB administration significantly reduced body weight, AGEs, MDA levels, increased SOD and GPx activity, improved GSH/GSSG ratio, and reduced IL-6 and TNF-α. Our findings suggest that short-term administration of TB decreases oxidative stress and reduces inflammation caused by HFFD and early estrogenic decline. These effects occurred via estrogen receptor alpha.

KEYWORDS:

• Overnutrition
• hippocampus
• high-fat-and-high-fructose diet
• oxidative stress
• inflammation
• estrogenic decline
• hormone receptors
• hormone receptor antagonists

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement (DAS)

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was supported by the Instituto Mexicano del Seguro Social [grant number R-2018-785-016].

Notes on contributors

Norma A. Estrada-Cruz

Norma Angélica Estrada-Cruz (4 publications) completed a BSc in Experimental Biology (Universidad Autónoma Metropolitana, Mexico City, Mexico), a MSc in Pharmacology (Instituto Politécnico Nacional, Mexico City), and a PhD in Experimental Biology (Universidad Autónoma Metropolitana, Mexico City). Has. Research: Oxidative stress in neurodegenerative diseases, mainly metabolic syndrome and type 2 diabetes mellitus, sex hormone neuroprotection and high-calorie diet models.

Leticia Manuel-Apolinar

Leticia Manuel Apolinar (55 publications) studied a BSc in Chemistry, an MSc in Pharmacology, and a PhD in Medicine Research; currently works as Titular Researcher A at the Mexican Institute of Social Security, Mexico City, Mexico. Research: Neuroendocrinology of intake regulation related to metabolic disorders such as obesity (adipokines) and diabetes.

Julia J. Segura-Uribe

Julia J. Segura-Uribe (19 publications) obtained a BSc in Chemistry (Universidad Nacional Autónoma de México, Mexico City, Mexico), MSc in Biochemistry (Universidad Nacional Autónoma de Mexico, Mexico City, Mexico), and a PhD in Medical Research (Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico). Research: Sex hormones neuroprotection and Alzheimer’s disease.

Julio C. Almanza-Pérez

Julio C Almanza-Perez (45 publications) obtained a BSc in Experimental Biology (Universidad Autónoma Metropolitana, Mexico City), a MSc in Experimental Biology (Universidad Autónoma Metropolitana, Mexico City), and a PhD in Experimental Biology (Universidad Autónoma Metropolitana, Mexico City). He continued his research as a Visiting Professor (Universidad Autónoma Metropolitana). Currently, he works as Titular Professor-Researcher C at the Universidad Autónoma Metropolitana-Iztapalapa. Research: Diabetes, obesity, inflammation, and drug research (dual PPAR agonist).

Ángeles Fortis-Barrera

Ángeles Fortis-Barrera (14 publications) has a PhD in Experimental Biology (Universidad Autónoma Metropolitana). Titular Professor-researcher B in Universidad Autónoma Metropolitana. Research: Obesity, diabetes, and hypertension, and the study of medicinal plants effects on these pathologies.

Sandra Orozco-Suárez

Sandra Orozco-Suárez (103 publications) obtained a BSc in Biology (Universidad Nacional Autónoma de México, Mexico City), and MSc and PhD in Biomedical Sciencies (Universidad Nacional Autónoma de Mexico, Mexico City). She continued her research as a postdoc in the Neuroanatomy department of the California University program (Irvine CA, USA). Currently, she works as Titular Researcher B at the Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico. Research: Pathophysiological mechanisms of drug-resistant epilepsy and neurodegenerative diseases in clinical studies and experimental models to test new drugs with anticonvulsant and anti-inflammatory potential.

Guadalupe Bautista-Poblet

Guadalupe Bautista-Poblet (1 publication) has a BSc in Experimental Biology (Universidad Autónoma Metropolitana, Mexico City, Mexico) and an MSc in Health Sciences (Instituto Politécnico Nacional, Mexico City, Mexico). Research: Oxidative stress, mainly in traumatic spinal cord injury, Neuroprotection with sex hormones, memory and learning.

Angélica Coyoy-Salgado

Ángelica Coyoy Salgado (11 publications) obtained a BSc in Pharmacobiological Chemistry (Universidad Nacional Autónoma de México, Mexico City), and a PhD in Biochemistry (Universidad Nacional Autónoma de Mexico, Mexico City). She continued her research as a postdoc at DGAPA-UNAM program (Universidad Nacional Autónoma de Mexico, Mexico City). Currently, she works as Professor Researcher at the Consejo Nacional de Ciencia y Tecnología (CONACYT) – Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico. Research: Spinal cord injury, cell death and oxidative stress.

Christian Guerra-Araiza

Christian Guerra-Araiza (55 publications) obtained a BSc in Biology (Universidad Nacional Autónoma de México, Mexico City), and a PhD in Biochemistry (Universidad Nacional Autónoma de Mexico, Mexico City). He continued his research as a postdoc at DGAPA-UNAM program (Instituto Cajal, Madrid, Spain). Research: Sex hormones and neuroprotection, Alzheimer disease, neurological effects of pollution and metabolic syndrome.