The Effects of Exercise Training and High Triglyceride Diet in an Estrogen Depleted Rat Model

Cardiovascular morbidity and mortality of premenopausal women are significantly lower compared to men of similar age. However, this protective effect evidently decreases after the onset of menopause. We hypothesized that physical exercise could be a potential therapeutic strategy to improve inflammatory processes and cardiovascular antioxidant homeostasis, which can be affected by the loss of estrogen and the adverse environmental factors, such as overnutrition. Ovariectomized (OVX, n= 40) and sham-operated (SO, n= 40) female Wistar rats were randomized to exercising (R) and non-exercising (NR) groups. Feeding parameters were chosen to make a standard chow (CTRL) or a high triglyceride diet (HT) for 12 weeks. Aortic and cardiac heme oxygenase (HO) activity and HO-1 concentrations significantly decreased in all of the NR OVX and SO HT groups. However, the 12-week physical exercise was found to improve HO-1 values. Plasma IL-6 concentrations were higher in the NR OVX animals and rats fed HT diet compared to SO CTRL rats. TNF-α concentrations were significantly higher in the NR OVX groups. 12 weeks of exercise significantly reduced the concentrations of both TNF-α and IL-6 compared to the NR counterparts. The activity of myeloperoxidase enzyme (MPO) was significantly increased as a result of OVX and HT diet, however voluntary wheel-running exercise restored the elevated values. Our results show that estrogen deficiency and HT diet caused a significant decrease in the activity and concentration of HO enzyme, as well as the concentrations of TNF-α, IL-6, and the activity of MPO. However, 12 weeks of voluntary wheel-running exercise is a potential non-pharmacological therapy to ameliorate these disturbances, which determine the life expectancy of postmenopausal women

Multiple Applications of Different Exercise Modalities with Rodents

A large proportion of chronic diseases can be derived from a sedentary lifestyle. Raising physical activity awareness is indispensable, as lack of exercise is the fourth most common cause of death worldwide. Animal models in different research fields serve as important tools in the study of acute or chronic noncommunicable disorders. With the help of animal-based exercise research, exercise-mediated complex antioxidant and inflammatory pathways can be explored, which knowledge can be transferred to human studies. Whereas sustained physical activity has an enormous number of beneficial effects on many organ systems, these animal models are easily applicable in several research areas. This review is aimed at providing an overall picture of scientific research studies using animal models with a focus on different training modalities. Without wishing to be exhaustive, the most commonly used forms of exercise are presented

The Effects of Exercise Training and High Triglyceride Diet in an Estrogen Depleted Rat Model: the Role of the Heme Oxygenase System and Inflammatory Processes in Cardiovascular Risk

L

Distinct Approaches of Raloxifene: Its Far-Reaching Beneficial Effects Implicating the HO-System

Selective estrogen receptor modulators (SERMs) were discovered in the mid-1900s in connection with estrogen-related pathological conditions. They were developed to antagonize the adverse effects of estrogen and have been shown to be effective against postmenopausal disorders manifested by estrogen deficiency. Raloxifene (RAL), one of the most widely used SERMs, expresses estrogen-like effects on bones, while it is found to be an antagonist on breast and uterus. RAL has multiple beneficial effects throughout the body, including antioxidant and anti-inflammatory properties, because of which it gains particular attention. Additionally, previous studies have revealed that RAL is an efficient modulator of heme-oxygenase (HO) expression. HO, through its general activity, participates in comprehensive cell defense processes, thus the induction of HO by RAL administration indicates a major role in its therapeutic efficacy. In this review, we compile the current knowledge about the overall metabolic, neurocognitive, and cardiovascular effects of RAL involving the cytoprotective HO-system

Cardioprotective effect of selective estrogen receptor modulator raloxifene are mediated by heme oxygenase in estrogen-deficient rat

Estrogens and raloxifene (RAL) have beneficial effects on certain cardiovascular indices in postmenopausal women characterized by estrogen deficiency. Heme oxygenase (HO) activity is increased by 17 beta-estradiol (E-2) and RAL in estrogen-deficient rat resulting in vasorelaxation mediated by carbon monoxide. We determined the expressions of HO in cardiac and aortic tissues after ovariectomy (OVX) and subsequent RAL or E-2 treatment. We investigated the effects of pharmacological inhibition of HO enzyme on the arginine vasopressin-(AVP-) induced blood pressure in vivo, the epinephrine- and phentolamine-induced electrocardiogram ST segment changes in vivo, and the myeloperoxidase (MPO) enzyme activity. When compared with intact females, OVX decreased the HO-1 and HO-2 expression, aggravated the electrocardiogram signs of heart ischemia and the blood pressure response to AVP, and increased the cardiac MPO. E-2 and RAL are largely protected against these negative impacts induced by OVX. The pharmacological inhibition of HO in E-2- or RAL-treated OVX animals, however, restored the cardiovascular status close to that observed in nontreated OVX animals. The decreased expression of HO enzymes and the changes in blood pressure ischemia susceptibility and inflammatory state in OVX rat can be reverted by the administration of E-2 or RAL partly through its antioxidant and anti-inflammatory roles