Ahmadi-Beni M, Mokhtarian K, Mobini GR
… +4 more, Najafi-Chaleshtori S, Salehi-Vanani N, Anjomshoa M, Houshmand F
Oxid Med Cell Longev
· 2026 · PMID 41823333
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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 saniti...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.
James C, Weber J, Boyd C
… +2 more, Fournier PA, Arthur PG
Oxid Med Cell Longev
· 2026 · PMID 41812060
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Australian football is a demanding contact sport where high training loads during the pre-season have been identified as a potential cause of non-contact injuries. The level of thiol-oxidised albumin, a marker of oxidati...Australian football is a demanding contact sport where high training loads during the pre-season have been identified as a potential cause of non-contact injuries. The level of thiol-oxidised albumin, a marker of oxidative stress, might be related to the training load, and thus could be used to indirectly quantify the impact of training loads upon an athlete. The aim of this study was to investigate whether the level of thiol-oxidised albumin was affected by the pre-season training load in a team of professional Australian Football League (AFL) athletes and compare the effect of lower pre-season training loads caused by COVID-19 restrictions on the level of thiol-oxidised albumin. Forty-five participants collected daily dried blood spots in the morning prior to each training session to measure thiol-oxidised albumin using a novel methodology (OxiDx). Training load, which was operationally defined as the total distance covered during training as well as distance at certain velocities, and change of direction (COD), was measured using global positioning units. There was an association (R = 0.12) between the level of thiol-oxidised albumin with; (1) total distance covered (p < 0.0001), (2) distance covered at 10-20 km/h (p < 0.0001) and 20-25 km/h (p = 0.0082) and (3) COD running (p = 0.0025). Training loads and the level of thiol-oxidised albumin were highest in the early pre-season and lowest at the conclusion of the pre-season, when training loads were reduced as a consequence of COVID-19. The measurement of the level of thiol-oxidised albumin may provide a means to indirectly quantify the impact of training loads upon an athlete, especially given the simplicity of the OxiDx methodology for fingertip blood sample collection.
Lama S, Venditti M, Biasi A
… +6 more, Lenti C, Najahi H, Banni M, Tenore GC, Novellino E, Stiuso P
Oxid Med Cell Longev
· 2026 · PMID 41757226
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BACKGROUND: Humans are constantly exposed to environmental microplastic (MP) particles, which can be absorbed through the gut and exert adverse health effects. This study aimed to investigate the harmful effects of envir...BACKGROUND: Humans are constantly exposed to environmental microplastic (MP) particles, which can be absorbed through the gut and exert adverse health effects. This study aimed to investigate the harmful effects of environmental polyethylene MPs (PE, 2.6 μm) on differentiated Caco-2 (D-Caco-2) intestinal epithelial cells and to assess the protective potential of apple polyphenol extract (LAPE). METHODS: D-Caco-2 cells were exposed to PE, LAPE, or their combination. Cell viability and lipid peroxidation were evaluated using MTT and TBARS assays, respectively. The organization of F-actin and alkaline phosphatase proteins was evaluated by immunofluorescence, whereas occludin and NF-κB were evaluated by Western blot analysis. RESULTS: PE reduced D-Caco-2 viability and impaired cell differentiation by increasing lipid peroxidation. In addition, PE destructured F-actin organization and altered the expression of occludin, a tight-junction protein. CONCLUSIONS: Our findings show that PE increases oxidative stress, triggering epithelial-mesenchymal transition and dedifferentiation in Caco-2 cells. Interestingly, LAPE, owing to its antioxidant and anti-inflammatory properties, counteracted the harmful effects of PE, suggesting its potential as a nutraceutical strategy to prevent MP-induced damage in the gastrointestinal (GI) tract.
Nukitram J, Kanjanavattana A, Rungruang P
… +8 more, Yotyatthai N, Kaewudom P, Promkasikorn P, Kaowsuwan P, Zaima N, Cheaha D, Thukhammee W, Wattanathorn J
Oxid Med Cell Longev
· 2026 · PMID 41694330
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The neuropharmacological benefits for sleep quality and mental health from the extracts of L. leaves (MA) and L. flowers (CT) have been revealed previously. However, due to synergistic interactions of polyherbal ingred...The neuropharmacological benefits for sleep quality and mental health from the extracts of L. leaves (MA) and L. flowers (CT) have been revealed previously. However, due to synergistic interactions of polyherbal ingredients, the positive effects of MA mixed with CT are still controversial. Preliminary outcomes from in vitro assessment exposed that a 3:1 ratio of MA:CT (MACT) yielded the highest antioxidant capacity and gamma-aminobutyric acid (GABA)-promoting activity among seven combination ratios: 0MA:1CT, 1MA:0CT, 1MA:1CT, 1MA:2CT, 1MA:3CT, 2MA:1CT, and 3MA:1CT. Male Wistar rats ( = 6/group) were electroencephalographically and electromyographically monitored to confirm the sedative-hypnotic function of the assigned ingredients over 3 h after oral administration. Cognitive and anxiolytic effects were also evaluated thereafter. Following drug administration, it was found that MACT exhibited positive influences in a dose-dependent manner (125, 250, and 500 mg/kg), and in a significantly better manner than either 500 mg/kg MA or CT alone. Interestingly, a majority of these effects, including sedative-hypnotic parameters, that is, decreasing of latency to rapid eye movements (REMs) sleep and wake duration, increasing of REM sleep duration, number of REM sleep bouts, as well as elevating of cognitive function and anxiolytic parameters was reversed by pretreatment with bicuculline methiodide (2 mg/kg), a GABA receptor antagonist. Overall, the advantages of MACT-based polyherbal drugs, which act preferentially on GABA receptors, may pave the way for further development of MACT as an alternative drug or food supplement for neuropharmacological improvements in GABA receptor-related disorders.
Anavi S, Giltman N, Zeigerman H
… +2 more, Madar Z, Tirosh O
Oxid Med Cell Longev
· 2026 · PMID 41684462
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BACKGROUND AND AIMS: Ferroptosis, a form of cell death marked by iron dysregulation and lipid peroxidation, has been implicated in liver and neurodegenerative diseases. 7-ketocholesterol (7KC), a cholesterol oxidation pr...BACKGROUND AND AIMS: Ferroptosis, a form of cell death marked by iron dysregulation and lipid peroxidation, has been implicated in liver and neurodegenerative diseases. 7-ketocholesterol (7KC), a cholesterol oxidation product, induces oxidative stress and inflammation at high concentrations. However, the effects of low, subtoxic levels of 7KC are unclear. This study investigates the potential hormetic effects of low concentrations of 7KC on hepatocytes and neuronal cells during ferroptosis. METHOD: Ferroptosis was induced in AML12 hepatocytes using 20 µM Erastin, with cells co-treated with varying concentrations of 7KC. Cell death was assessed, and gene expression was analyzed via RNA sequencing (RNA-seq) and real-time PCR. HT4 hippocampal neuronal cells were treated with glutamate to induce ferroptosis, both with and without 7KC. RESULTS: Low, nontoxic concentrations of 7KC protected both hepatocytes and neuronal cells from ferroptosis induced by Erastin and glutamate, respectively. In contrast, higher concentrations of 7KC increased cell death. 7KC's protective effects in hepatocytes were linked to lower malondialdehyde (MDA) levels and reduced peroxidation of polyunsaturated fatty acids (PUFAs). The cholesterol synthesis pathway, as well as lipid accumulation, was suppressed by 7KC. Conversely, these processes were upregulated by Erastin. Notably, 7KC showed a stronger anti-ferroptotic effect than 7-dehydrocholesterol (7DHC) at low concentrations, possibly through Nrf2-independent upregulation of the gamma-glutamylcysteine ligase catalytic (GCLC) unit. CONCLUSION: This study reveals that 7KC can have a hormetic effect on ferroptosis at low concentrations, suggesting a potential advantage. Further research is needed to clarify the underlying mechanisms, particularly regarding GCLC upregulation.
Mehrtash M, Salesi M, Daryanoosh F
… +2 more, Tanideh N, Jamhiri I
Oxid Med Cell Longev
· 2026 · PMID 41659161
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BACKGROUND/AIMS: Obesity and insulin resistance induced by excessive calorie intake remain major health challenges. Caloric restriction (CR) and resistance training (RT) are known strategies to improve metabolic health,...BACKGROUND/AIMS: Obesity and insulin resistance induced by excessive calorie intake remain major health challenges. Caloric restriction (CR) and resistance training (RT) are known strategies to improve metabolic health, but their combined effects on lipid droplet-associated proteins and metabolic regulators remain unclear. This study aimed to evaluate the impact of CR and RT, alone and in combination (CR + RT), on lipid droplet-associated proteins and signaling pathways in rats exposed to a high-fat diet (HFD). METHODS: Fifty male Sprague-Dawley rats were fed HFD for 8 weeks and were then randomly assigned to five groups: HFD, normal-fat diet (NFD), CR, RT, and CR + RT. Each intervention was performed for 8 weeks following the initial 8-week HFD induction. Body weight, insulin resistance index (HOMA-IR), and mRNA expression of perilipin 1 was measured in both adipose and skeletal muscle tissues, whereas perilipin 5, fat-specific protein 27 (FSP-27), adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1), sirtuin 1 (SIRT1), and AMP-activated protein kinase (AMPK) were measured only in skeletal muscle after the subsequent 8-week intervention period. RESULTS: At baseline, no significant differences in body weight were observed among the groups ( > 0.05). After 16 weeks, rats in HFD group exhibited the highest body weight (509.8 ± 6.0g), whereas CR + RT group showed the most pronounced reduction (292.2 ± 1.8 g; < 0.001). Insulin resistance (HOMA-IR) was significantly elevated in the HFD group (5.55 ± 0.21) compared to all other groups, while the CR + RT group demonstrated the lowest value (1.24 ± 0.05), comparable to the normal diet group ( > 0.05). At the molecular level, CR + RT downregulated perilipin 1 and FSP-27, while significantly upregulating ATGL, AMPK, SIRT1, and PGC-1 compared to HFD (all < 0.05). CONCLUSION: Combined CR and RT produced superior benefits over either intervention alone, improving insulin sensitivity and lipid metabolism through coordinated regulation of lipid droplet proteins and metabolic signaling pathways. These findings suggest CR+RT as an effective strategy against diet-induced obesity.
Rabiee F, Fattahi M, Iranzad M
… +5 more, Rahimi Andani M, Jafarpour F, Sanei MH, Drevet JR, Nasr-Esfahani MH
Oxid Med Cell Longev
· 2026 · PMID 41586152
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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...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.
Reveyaz MA, Peyronnel C, Boëte Q
… +8 more, Fournier J, Arnaud C, Belaïdi E, Harki O, Pépin JL, Khouri C, Faury G, Briançon-Marjollet A
Oxid Med Cell Longev
· 2026 · PMID 41541542
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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 functi...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.
Hamadi N, Nemmar A, Beegam S
… +3 more, Zaaba NE, Elzaki O, Nemmar A
Oxid Med Cell Longev
· 2026 · PMID 41523312
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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...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 ( < 0.05- < 0.0001). Additionally, concentrations of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were significantly increased in both groups ( < 0.01- < 0.0001). Notably, only the Reg-HS regimen induced a substantial rise in plasma levels of indoxyl sulfate, cystatin C, and adiponectin ( < 0.01- < 0.0001). Similarly, relative to the control group, mice subjected to Reg-HS exposure exhibited significantly elevated levels of proinflammatory cytokines, tumor necrosis factor-, and interleukin-6 ( < 0.0001). Exposure to either Occ-HS or Reg-HS caused significant increase in interleukin-1 ( < 0.05, < 0.0001), thiobarbituric acid reactive substances (TBARS; < 0.05, < 0.0001) compared with air-exposed mice. Our findings revealed that Occ-HS inhalation triggered only a decrease in superoxide dismutase (SOD) activity ( < 0.001). On the other hand, nitric oxide (NO; < 0.001), SOD ( < 0.0001), and Glutathione (GSH; < 0.0001) levels were significantly decreased in Reg-HS group. Furthermore, DNA damage marker, 8-Hydroxy-2-deoxyguanosine was significantly augmented in both regimens ( < 0.0001). Exposure to both regimens resulted in significant elevation in mitochondrial complexes I, II and III, and IV ( < 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 ( < 0.001- < 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.