Oxidative Medicine and Cellular Longevity最新文献

[This corrects the article DOI: 10.1155/2021/8830880.].

Infertility, a major global health problem affecting ~17.5% of couples, is influenced by various intrinsic (e.g., individual genetics) and extrinsic (e.g., related to environmental stimuli) factors. Oxidative stress and reactive oxygen species (ROS) are at the crossroads of these different stimulus-response pathways for both male and female gametes. While ROS are essential for ovarian processes such as folliculogenesis and oocyte maturation, changes in the ovarian ROS generation/recycling equilibrium can lead to impaired reproductive outcomes. Against this backdrop, noninvasive therapeutic approaches aimed at supplementing antioxidant (AO) molecules have emerged to correct prooxidant imbalances encountered in various stress situations. Numerous molecules have been tested, alone or in combination, for their beneficial effects on reproductive success in both men and women. The aim of this study was to investigate the effects of vitamin E supplementation at different levels on female reproductive performance and the molecular pathways involved. Groups of mice were treated with three different doses of vitamin E (optimal, overdose and severe overdose) and compared with control groups (no supplementation, sham groups [water and olive oil]). The results showed that both overdose and severe overdose of vitamin E showed significant reductions in pregnancy rates, litter size, and oocyte development capacity compared to the other groups. Blastocyst formation rates and quality were also significantly lower in these vitamin E overdosed groups, reflecting compromised embryonic quality. Severe vitamin E overdosage resulted in impaired folliculogenesis, with fewer antral follicles and corpora lutea and an increased number of atretic follicles. Notably, uterine thickness was significantly reduced in the severe vitamin E overdose group. Molecular analyses revealed increased GSH/GSSG ratios and higher ROS levels in granulosa cells. Intriguingly, in a context of increased ROS, we did not record any stimulation of the Nrf2 pathway and associated genes. A decrease in apoptosis in the ovarian environment marked by a lower Bax/Bcl2 ratio accompanied situations of vitamin E overdose. These findings shed new light on the consequences of excessive vitamin E intake and its implications for reproductive health. While optimal supplementation promotes fertility, excessive intake disrupts the redox balance, adversely affecting ovarian function and reproductive outcomes. This study highlights the importance of precise AO management to mitigate stress-induced infertility and provides a framework for further research into the molecular mechanisms underlying vitamin E's effects on ovarian physiology.

Objectives: Obstructive sleep apnea (OSA) and the related intermittent hypoxia (IH) are recognized as major cardiovascular risk factors. In a previous meta-analysis, we confirmed the impact of IH on structural and functional remodeling of vessels in rodent models of IH. Here, we conducted a systematic review and meta-analysis to investigate the molecular mechanisms related to vascular remodeling induced by IH and to analyze the impacts of patterns of exposure on the effect of IH.

Methods: We searched PubMed, Web of Science, and EMBASE and included 52 articles, among them 44 concerning wild type (WT) rodents and eight concerning apolipoprotein E knockout (ApoE^-/-) mice. We used standardized mean difference (SMD) to compare results between studies. A hypoxic score was designed and calculated, and metaregressions were performed to explore the impact of IH exposure parameters on the selected outcomes.

Results: IH induced an increase in oxidative stress, inflammation markers, leucocyte infiltration, and apoptosis, and a decrease in endothelial nitric oxide synthase (eNOS) expression and activity in arteries of WT mice. In metaregressions, inflammation and oxidative stress markers were associated with total duration of IH exposure, and eNOS was associated with hypoxic score. In ApoE^-/- mice, inflammation markers were significantly increased in atherosclerotic plaques, but leukocyte infiltration and oxidative stress were not modified by IH. Rodent characteristics had only few impacts on the outcomes.

Conclusions: Our meta-analysis confirms that IH, independently of measured confounders, has a major impact on oxido-inflammatory mechanisms in vessels, and that the duration of IH can modulate these effects. Our findings strengthen our understanding of molecular mechanisms associated with vascular alterations in IH/OSA.

[This corrects the article DOI: 10.1155/2015/358396.].

[This corrects the article DOI: 10.1155/2022/6371048.].

Regular hookah smoking (Reg-HS) has become a major global public health issue, linked to significant health risks, including kidney damage. A less frequent pattern of use, known as occasional hookah smoking (Occ-HS), is also common; however, there has been little progress in understanding the direct impact of Occ-HS on kidneys. To investigate how varying frequencies of HS inhalation affect the kidney, we exposed mice to nose-only HS under two regimens, occasional (30 min once weekly) and regular (30 min five times per week) for a duration of 6 months. This study explored the impact on renal damage, inflammatory responses, oxidative stress levels, genotoxicity, and mitochondrial activity as well as the possible modulation of MAPK signaling pathway. Both Occ-HS and Reg-HS led to a marked elevations in plasma levels of urea and creatinine (p < 0.05-p < 0.0001). Additionally, concentrations of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were significantly increased in both groups (p < 0.01-p < 0.0001). Notably, only the Reg-HS regimen induced a substantial rise in plasma levels of indoxyl sulfate, cystatin C, and adiponectin (p < 0.01-p < 0.0001). Similarly, relative to the control group, mice subjected to Reg-HS exposure exhibited significantly elevated levels of proinflammatory cytokines, tumor necrosis factor-α, and interleukin-6 (p < 0.0001). Exposure to either Occ-HS or Reg-HS caused significant increase in interleukin-1β (p < 0.05, p < 0.0001), thiobarbituric acid reactive substances (TBARS; p < 0.05, p < 0.0001) compared with air-exposed mice. Our findings revealed that Occ-HS inhalation triggered only a decrease in superoxide dismutase (SOD) activity (p < 0.001). On the other hand, nitric oxide (NO; p < 0.001), SOD (p < 0.0001), and Glutathione (GSH; p < 0.0001) levels were significantly decreased in Reg-HS group. Furthermore, DNA damage marker, 8-Hydroxy-2^'-deoxyguanosine was significantly augmented in both regimens (p < 0.0001). Exposure to both regimens resulted in significant elevation in mitochondrial complexes I, II and III, and IV (p < 0.0001). Increased expression of activation of mitogen-activated protein kinases (MAPKs) was observed exclusively in the Reg-HS group, as evidenced by increased levels of p-JNK, p-p38, and p-ERK (p < 0.001-p < 0.0001). In conclusion, our study is the first to demonstrate that despite the significant differences in the amount of smoke inhaled, both Occ-HS or Reg-HS inhalation deteriorate kidney function and induce oxidative damage, inflammatory response, DNA injury, and mitochondrial impairment with modulation of the MAPK signaling. These findings highlight the importance of further research into the public health risks associated with occasional hookah smoking.

[This retracts the article DOI: 10.1155/2019/2432416.].

Myocardial infarction (MI) remains a leading cause of mortality worldwide, with type 2 MI (T2MI) carrying a worse prognosis than type 1 MI (T1MI). The hygiene hypothesis suggests that reduced microbial exposure in sanitized environments contributes to immune dysregulation and inflammation-related diseases. While helminth therapy has shown potential in modulating the inflammatory responses in myocardial injury, its effects on oxidative stress remain underexplored. We hypothesize that Fasciola hepatica total protein extract (FhTE) attenuates myocardial injury in T2MI via immune modulation consistent with the hygiene hypothesis, affecting both inflammation and oxidative stress. To investigate this, male Wistar rats were pretreated with FhTE (2.5 mg/kg, intraperitoneally) daily for 6 days. MI was induced by subcutaneous isoproterenol (100 mg/kg) on days five and six. Electrocardiographic analysis 24 h post-final treatment revealed that FhTE pretreatment attenuated MI-induced changes. FhTE reduced cardiac hypertrophy and decreased serum cardiac injury markers. It enhanced antioxidant defense by increasing superoxide dismutase (SOD) and catalase (CAT) activities, lowering nitric oxide (NO) and malondialdehyde (MDA) levels, and modulating nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA levels. FhTE also reduced neutrophil and M1 macrophage activity, evidenced by decreased myeloperoxidase (MPO) levels and inducible nitric oxide synthase (iNOS) mRNA expression, and downregulated inflammatory cytokine genes (IL-1β, IL-6, TNF-⍺, and IL-33). FhTE demonstrates significant cardioprotective effects by modulating inflammation and oxidative stress, thereby preconditioning the myocardium against T2MI. These findings offer robust experimental support for the hygiene hypothesis in the context of ischemic heart disease, highlighting its potential for novel MI therapies.