Oxidative Stress as a Therapeutic Target of Cardiac Remodeling.

Cardiac remodeling is defined as a group of molecular, cellular, and interstitial changes that clinically manifest as changes in the heart's size, mass, geometry, and function after different stimuli. It is important to emphasize that remodeling plays a pathophysiological role in the onset and progression of ventricular dysfunction and subsequent heart failure. Therefore, strategies to mitigate this process are critical. Different factors, including neurohormonal activation, can regulate the remodeling process and increase cell death, alterations in contractile and regulatory proteins, alterations in energy metabolism, changes in genomics, inflammation, changes in calcium transit, metalloproteases activation, fibrosis, alterations in matricellular proteins, and changes in left ventricular geometry, among other mechanisms. More recently, the role of reactive oxygen species and oxidative stress as modulators of remodeling has been gaining attention. Therefore, this review assesses the role of oxidative stress as a therapeutic target of cardiac remodeling.

Role of Nutrients and Foods in Attenuation of Cardiac Remodeling through Oxidative Stress Pathways.

Cardiac remodeling is defined as a group of molecular, cellular, and interstitial changes that manifest clinically as changes in the heart's size, mass, geometry, and function after different injuries. Importantly, remodeling is associated with increased risk of ventricular dysfunction and heart failure. Therefore, strategies to attenuate this process are critical. Reactive oxygen species and oxidative stress play critical roles in remodeling. Importantly, antioxidative dietary compounds potentially have protective properties against remodeling. Therefore, this review evaluates the role of nutrients and food as modulators of cardiac remodeling.

Parental exposure to benzo(a)pyrene in the peripubertal period impacts reproductive aspects of the F1 generation in rats.

Benzo(a)pyrene (BaP) is an ubiquitous environmental pollutant which can lead to adverse effects on male reproduction. However, the persistence of these changes on a multigenerational scale has not been sufficiently explored. This study evaluated if peripubertal exposure to BaP in male rats can induce reproductive impairment in offspring. Male rats received BaP at environmentally relevant doses (0, 0.1, 1, or 10 µg/kg/day) orally from post-natal (PND) 23-53. On PND 90, treated males were mated with non-treated females for obtaining the next generation (F1). The paternal exposure to BaP decreased the body weight of offspring on PND 1, 13 and 22, as well as it provoked a reduction in the relative anogenital distance of the males. This exposure also brought forward the onset of puberty, evidenced by an earlier vaginal opening and first estrous in females of the lowest dose group and by a delay in the testicular descent and preputial separation ages in males. The males presented a decrease in the daily sperm production and a disrupted sperm morphology. Furthermore, the testicular histology was altered, evidenced by a reduction in the Leydig cell numbers and in the seminiferous tubules diameter, as well as a disrupted seminiferous tubules staging. The estrous cyclicity and some fertility parameters were changed in the females, as well as alterations in the ovary and uterus histology were observed. BaP compromised several reproductive parameters of the F1 generation, suggesting that peripubertal exposure to this compound provokes permanent modifications in male germ line of F0 generation.

Exposure to benzo(a)pyrene from juvenile period to peripubertal impairs male reproductive parameters in adult rats.

Benzo(a)pyrene (BaP) is a persistent organic pollutant and endocrine disruptor that can compromise the steroidogenesis process by interacting with the StAR protein, causing adverse effects on male reproduction. However, consequences of prepubertal BaP exposure and its impacts on adult life are yet unknown. This study investigated the effects of BaP exposure from the juvenile period to peripubertal on reproductive parameters in adult male rats. Males were exposed to 0; 0.1; 1 or 10 µg/kg/day of BaP from post-natal (PND) 23 to PND 53 (by gavage). The lowest dose of BaP was able to compromise the male copulatory behavior, as evidenced by the delay in the first mount, intromission and ejaculation. Furthermore, BaP-treated groups showed lower sperm quality (disrupted motility and morphology) and quantity, reduced relative weights of the thyroid and seminal gland. Serum testosterone levels and the Leydig cells nuclei volume were decreased by BaP exposure whereas the StAR expression was increased. Histopathological changes in the testis also were detected in the males exposed to BaP. These results showed that prepubertal BaP-exposure adversely influenced the male reproductive system in the adult life, indicating that a comprehensive risk assessment of BaP-exposure on prepubertal period is necessary.

Maternal exposure to ibuprofen can affect the programming of the hypothalamus of the male offspring.

Ibuprofen, a non-steroidal anti-inflammatory drug, inhibits the activity of cyclooxygenase enzyme, leading to reduction in Prostaglandin E2 (PGE2) production. Due to the importance of PGE2 in promoting the brain masculinization in male fetus, this study aimed to evaluate the effects of in utero and lactational exposure to ibuprofen and their late repercussions on reproductive parameters in male rats. Pregnant rats were exposed to ibuprofen (10, 30 or 60 mg/kg) or vehicle (control group) per gavage daily from gestational day 15 to day 21 after birth, and late reproductive effects were assessed during the sexual development and in the reproductive adult life in the male offspring. Males exposed to ibuprofen had a decrease in body weight and anogenital distance, as well as a delay in the ages of testicular descent and preputial separation. In adulthood, there was a decrease in the Leydig cells nuclei volume, testosterone levels and percentage of normal sperm morphology. All animals exposed to ibuprofen presented male copulatory behavior, however, in the presence of another male, they also presented a female-typical behavior. Maternal exposure to ibuprofen during the sensitive windows of brain development adversely impacted the reproductive parameters of male rats, suggesting an incomplete masculinization of the hypothalamus.

Effects of exposure to ethanolic extract from Achyrocline satureioides (Lam.) D.C. flowers on reproductive and developmental parameters in Wistar rats.

Achyrocline satureioides (LAM) D.C. is a species plant used in folk medicine with several medicinal properties; however, few studies have focused on its potential adverse effects. The aim of this study was to examine the effects of ethanolic extract of A. satureioides flowers administered during pre-mating, mating, pregnancy and postpartum period on reproductive and developmental parameters in rats. Male and female rats received by gavage 0, 250, 500 or 750 mg/kg of extract. The animals were treated from pre-mating until 13 days post-partum. Phytochemical analysis revealed the presence of important flavonoids (quercetin, luteolin, caffeic acid, rutin, and ferulic acid). In females, biochemical, hematological or gestational parameters were not markedly altered by the extract. However, an increase in calcium and thyroid stimulating hormone (TSH) levels was found in treated-dams. Although TSH and T4 levels were not significantly altered in pups, there was a rise in body weight of pups whose mothers were treated with the extract. All males treated were able to successfully copulate with treated-females. However, rats exposed to 500 and 750 mg/kg of extract exhibited a significant decrease in daily testicular sperm production and delay in sperm transit time in the epididymis. The ethanolic extract of A. satureioides flowers produced adverse effects in the male reproductive system as evidenced by diminished sperm production and transport. In addition, the extract elevated TSH levels of exposed mothers which may consequently affect the development of pups but this requires further evaluation.