The aim of this study was to investigate the effect of aging and ovariectomy on various physiological parameters related to inflammation and oxidative stress in livers obtained from old female rats, and the influence of chronic administration of melatonin on these animals. Twenty‐four female Wistar rats of 22 months of age were used. Animals were divided into four experimental groups: two intact groups that were untreated or given melatonin (1 mg/kg/day), and two ovariectomized groups that also untreated and treated with melatonin (1 mg/kg/day). After 10 wk of treatment, rats were sacrificed by decapitation, and livers were collected and homogenized. A group of 2‐month‐old female rats was used as young controls. Protein expression of inducible nitric oxide synthase (iNOS), heme oxygenase‐1 (HO‐1), IL‐6, TNF‐α and IL‐1β were determined by Western blot analysis. The levels of nitric oxide metabolites (NOx), lipid hydroperoxide (LPO), TNF‐α, IL‐1β, IL‐6 and IL‐10 were determined. Levels of LPO in the liver homogenates as well as iNOS protein expression and NOx levels were increased in old rats as compared with young animals; this effect was more evident in ovariectomized animals. Pro‐inflammatory cytokines TNF‐α, IL‐1β and IL‐6 were significantly increased and anti‐inflammatory IL‐10 decreased during aging and after ovariectomy. Aging also significantly increased the expression of HO‐1 protein, and ovariectomized rats showed an additional increase. Administration of melatonin, both to intact and to the ovariectomized animals significantly reduced NOx, LPO levels and pro‐inflammatory cytokines in the liver as compared with untreated rats. Significant rice in IL‐10 and reductions in the iNOS, HO‐1, IL‐6, TNF‐α and IL‐1β protein expression were also found in rats treated with melatonin. Oxidative stress and inflammation induced during aging in the liver are more marked in castrated than in intact females. Administration of melatonin reduces both these situations.
The aim of our study was to elucidate the role of growth hormone (GH) replacement therapy in three of the main mechanisms involved in sarcopenia: alterations in mitochondrial biogenesis, increase in oxidative stress, and alterations in protein balance. We used young and old Wistar rats that received either placebo or low doses of GH to reach normal insulin-like growth factor-1 values observed in the young group. We found an increase in lean body mass and plasma and hepatic insulin-like growth factor-1 levels in the old animals treated with GH. We also found a lowering of age-associated oxidative damage and an induction of antioxidant enzymes in the skeletal muscle of the treated animals. GH replacement therapy resulted in an increase in the skeletal muscle protein synthesis and mitochondrial biogenesis pathways. This was paralleled by a lowering of inhibitory factors in skeletal muscle regeneration and in protein degradation. GH replacement therapy prevents sarcopenia by acting as a double-edged sword, antioxidant and hypertrophic.
The aim of this study was to determine the concentrations of oxidative stress markers, antioxidant enzymes and cytokines in the follicular fluid of young women with low response in ovarian stimulation cycles compared with high responders and fertile oocyte donors of the same age, to assess the impact of oxidative stress on ovarian reserve. The activity of follicular fluid antioxidant enzymes glutathione transferase, glutathione reductase and glutathione peroxidase was significantly lower in young women with reduced ovarian reserve compared with that in high responders and oocyte donors. Follicular fluid concentrations of oxidative stress marker malondialdehyde combined with 4-hydroxyalkenals and nitric oxide were higher in low responders than in high responders and oocyte donors. Significant differences between low responders and donors in concentrations of IL-2, IL-6, IL-8 and vascular endothelial growth factor were observed, with higher concentrations in low responders. However, IL-10 concentration was lower in low responders than in high responders and donors. No significant differences were found in follicular fluid concentrations of tumour necrosis factor alpha between the three groups. These results demonstrate that different concentrations of oxidative stress markers, oxidant enzymes and cytokines in low responders compared with high responders and oocyte donors may negatively impact ovarian response.
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