Chronic Testosterone Replacement Exerts Cardioprotection against Cardiac Ischemia-Reperfusion Injury by Attenuating Mitochondrial Dysfunction in Testosterone-Deprived Rats

Pongkan, Wanpitak; Chattipakorn, Nipon

doi:10.1371/journal.pone.0122503

Cited by 60 publications

(53 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The weight loss found in NDO rats could be due to decreased food intake. This finding is consistent with previous studies, which reported that an orchiectomy could cause permanent hypophagia (Gentry & Wade 1976), an increase in oxidative stress (Pongkan et al 2015), and an increase in leptin (Baumgartner et al 1999). The possible mechanism for this could be due to the induction of proinflammatory cytokines (via nuclear factor-κ-B signaling molecules) causing oxidative stress (Vlantis & Pasparakis 2010).…”

Section: Discussionsupporting

confidence: 92%

“…The possible mechanism could be due to the increasing level of plasma and cardiac MDA, and increased cardiac mitochondrial ROS production in HFO rats. The increase in the level of oxidative stress in the heart may have aggravated an apoptotic pathway (Zorov et al 2006) and led to a decrease in anti-apoptotic (BCL2) levels, and an increase in pro-apoptotic protein (BAX) levels (Pongkan et al 2015), therefore, leading to cardiomyocyte apoptosis and finally LV dysfunction (Aon et al 2009). …”

Section: Metabolic Disturbancementioning

confidence: 99%

“…High-dose testosterone also increased oxidative stress levels by decreasing the expression of endothelial nitric oxide synthase and consequently the formation of NO, resulting in endothelial dysfunction (Skogastierna et al 2014). Moreover, in an ischemia and reperfusion (I/R) injury rabbit model, supraphysiological level of testosterone increased fibrosis and oxidative stress and exacerbated such detrimental effects of I/R (Chuang et al 2013), whereas testosterone replacement at the physiological level exerted antioxidative effects by reducing mitochondrial oxidative stress (Pongkan et al 2015, Pintana et al 2015b) and serum MDA levels (Pintana et al 2015b). …”

Section: Metabolic Disturbancementioning

confidence: 99%

“…The prevalence of testosterone deficiency increases substantially with age (Araujo et al 2007) and is associated with the development of several disorders including obesity, dyslipidemia, insulin resistance, metabolic syndrome, and cardiovascular disease (Grossmann et al 2008, Oskui et al 2013. Moreover, testosterone deprivation alone significantly induces left ventricular (LV) contractile dysfunction and cardiac sympathovagal imbalance in orchiectomized rats (Pongkan et al 2015).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Testosterone deprivation accelerates cardiac dysfunction in obese male rats

Pongkan

Pintana

Sivasinprasasn

et al. 2016

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Low testosterone level is associated with increased risks of cardiovascular diseases. As obese-insulin-resistant condition could impair cardiac function and that the incidence of obesity is increased in aging men, a condition of testosterone deprivation could aggravate the cardiac dysfunction in obese-insulin-resistant subjects. However, the mechanism underlying this adverse effect is unclear. This study investigated the effects of obesity on metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function in testosterone-deprived rats. Orchiectomized or sham-operated male Wistar rats (n=36per group) were randomly divided into groups and were given either a normal diet (ND, 19.77% of energy fat) or a high-fat diet (HFD, 57.60% of energy fat) for 12weeks. Metabolic parameters, HRV, LV function, and cardiac mitochondrial function were determined at 4, 8, and 12weeks after starting each feeding program. We found that insulin resistance was observed after 8weeks of the consumption of a HFD in both sham (HFS) and orchiectomized (HFO) rats. Neither the ND sham (NDS) group nor ND orchiectomized (NDO) rats developed insulin resistance. The development of depressed HRV, LV contractile dysfunction, and increased cardiac mitochondrial reactive oxygen species production was observed earlier in orchiectomized (NDO and HFO) rats at week 4, whereas HFS rats exhibited these impairments later at week 8. These findings suggest that testosterone deprivation accelerates the impairment of cardiac autonomic regulation and LV function via increased oxidative stress and impaired cardiac mitochondrial function in obese-orchiectomized male rats.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Metabolic Disturbancementioning

confidence: 99%

Section: Metabolic Disturbancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Testosterone deprivation accelerates cardiac dysfunction in obese male rats

Pongkan

Pintana

Sivasinprasasn

et al. 2016

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Orchiectomy was performed using the method described in previous studies (Dulisch 1976, Pongkan et al 2015.…”

Section: Orchiectomy Proceduresmentioning

confidence: 99%

Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats

Potikanond¹,

Rattanachote²,

Pintana³

et al. 2016

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

The present study aimed to test the hypothesis that testosterone deprivation impairs osteoblastic insulin signaling, decreases osteoblast survival, reduces bone density, and that obesity aggravates those deleterious effects in testosterone-deprived rats. Twenty four male Wistar rats underwent either a bilateral orchiectomy (O, nZ12) or a sham operation (S, nZ12). Then the rats in each group were further divided into two subgroups fed with either a normal diet (ND) or a high-fat diet (HF) for 12 weeks. At the end of the protocol, blood samples were collected to determine metabolic parameters and osteocalcin ratios. The tibiae were collected to determine bone mass using microcomputed tomography and for osteoblast isolation. The results showed that rats fed with HF (sham-operated HF-fed rats (HFS) and ORX HF-fed rats (HFO)) developed peripheral insulin resistance and had decreased trabecular bone density. In ND-fed rats, only the ORX ND-fed rats (NDO) group had decreased trabecular bone density. In addition, osteoblastic insulin resistance, as indicated by a decrease in tyrosine phosphorylation of the insulin receptor and Akt, were observed in all groups except the sham-operated ND-fed rats (NDS) rats. Those groups, again with the exception of the NDS rats, also had decreased osteoblastic survival. No differences in the levels of osteoblastic insulin resistance and osteoblastic survival were found among the NDO, HFS, and HFO groups. These findings suggest that either testosterone deprivation or obesity alone can impair osteoblastic insulin signaling and decrease osteoblastic survival leading to the development of osteoporosis. However, obesity does not aggravate those deleterious effects in the bone of testosterone-deprived rats.

show abstract

Mechanisms of Sex Disparities in Cardiovascular Function and Remodeling

Chaudhari

Cushen

Osikoya

et al. 2018

Comprehensive Physiology

View full text Add to dashboard Cite

Epidemiological studies demonstrate disparities between men and women in cardiovascular disease prevalence, clinical symptoms, treatments, and outcomes. Enrollment of women in clinical trials is lower than men, and experimental studies investigating molecular mechanisms and efficacy of certain therapeutics in cardiovascular disease have been primarily conducted in male animals. These practices bias data interpretation and limit the implication of research findings in female clinical populations. This review will focus on the biological origins of sex differences in cardiovascular physiology, health, and disease, with an emphasis on the sex hormones, estrogen and testosterone. First, we will briefly discuss epidemiological evidence of sex disparities in cardiovascular disease prevalence and clinical manifestation. Second, we will describe studies suggesting sexual dimorphism in normal cardiovascular function from fetal life to older age. Third, we will summarize and critically discuss the current literature regarding the molecular mechanisms underlying the effects of estrogens and androgens on cardiac and vascular physiology and the contribution of these hormones to sex differences in cardiovascular disease. Fourth, we will present cardiovascular disease risk factors that are positively associated with the female sex, and thus, contributing to increased cardiovascular risk in women. We conclude that inclusion of both men and women in the investigation of the role of estrogens and androgens in cardiovascular physiology will advance our understanding of the mechanisms underlying sex differences in cardiovascular disease. In addition, investigating the role of sex‐specific factors in the development of cardiovascular disease will reduce sex and gender disparities in the treatment and diagnosis of cardiovascular disease. © 2019 American Physiological Society. Compr Physiol 9:375‐411, 2019.

show abstract

Chronic Testosterone Replacement Exerts Cardioprotection against Cardiac Ischemia-Reperfusion Injury by Attenuating Mitochondrial Dysfunction in Testosterone-Deprived Rats

Cited by 60 publications

References 54 publications

Testosterone deprivation accelerates cardiac dysfunction in obese male rats

Testosterone deprivation accelerates cardiac dysfunction in obese male rats

Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats

Mechanisms of Sex Disparities in Cardiovascular Function and Remodeling

Contact Info

Product

Resources

About