-
Cureus May 2024People are constantly exposed to formaldehyde, a volatile and poisonous gas, in indoor environments. In particular, anatomists, pathologists, histologists, and those...
INTRODUCTION
People are constantly exposed to formaldehyde, a volatile and poisonous gas, in indoor environments. In particular, anatomists, pathologists, histologists, and those involved in embalming are exposed to higher amounts of formaldehyde continuously due to their work. This study aimed to investigate the effect of N-acetylcysteine on endostatin and humanin values in male rats exposed to experimental formaldehyde.
METHODS
In the study, 28 male Spraque-Dawley rats aged 12-14 weeks (seven animals in each group: control group, formaldehyde group, N-acetylcysteine group, formaldehyde+N-acetylcysteine group) were used. Four weeks later, the animals were sacrificed by decapitation. Following decapitation, endostatin and humanin levels in the serum of rats were studied by the enzyme-linked immunoassay (ELISA) method. In all analyses, p<0.05 was accepted as statistically significant.
RESULTS
Humanin and endostatin values were checked in the serum of rats. When humanin levels were compared between groups, a statistically significant difference was found between the formaldehyde group and both the control group (p<0.05) and the N-acetylcysteine group (p<0.05). In the formaldehyde+N-acetylcysteine group, it was determined that the humanin level was impaired due to formaldehyde exposure, approaching the control group values with the administered N-acetylcysteine. When the endostatin level was compared between the groups, a statistical significance (p<0.05) was found only between the formaldehyde group and the N-acetylcysteine group. In the formaldehyde+N-acetylcysteine group, it was determined that the endostatin level was impaired due to formaldehyde exposure, approaching the control group values with the administered N-acetylcysteine.
CONCLUSION
In this study, the effects of N-acetylcysteine on humanin and endostatin on rats exposed to formaldehyde were demonstrated for the first time. Formaldehyde exposure negatively affected humanin and endostatin levels in rat sera. N-acetylcysteine ameliorated the negative effects of formaldehyde, bringing humanin and endostatin levels closer to the healthy control group.
PubMed: 38947691
DOI: 10.7759/cureus.61354 -
European Review For Medical and... Jun 2024Eur Rev Med Pharmacol Sci 2023; 27 (24): 12103-12111-DOI: 10.26355/eurrev_202312_34808-PMID: 38164872, published online on December 22, 2023. After publication, the...
Eur Rev Med Pharmacol Sci 2023; 27 (24): 12103-12111-DOI: 10.26355/eurrev_202312_34808-PMID: 38164872, published online on December 22, 2023. After publication, the authors found that Table III's legend was the same as that of Table II. Therefore, Table III's legend has been corrected as follows: Table III. Plasma PK parameters following repeat doses of IV NAC 600 mg (n = 24). There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34808.
PubMed: 38946388
DOI: 10.26355/eurrev_202406_36449 -
Transplantation and Cellular Therapy Jun 2024Transplant associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic cell transplant (HCT) associated with endothelial injury resulting in severe...
BACKGROUND
Transplant associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic cell transplant (HCT) associated with endothelial injury resulting in severe end organ damage, acute and long-term morbidity, and mortality. Myeloablative conditioning is a known risk factor, though specific causative agents have not been identified. We hypothesized that the combination of cyclophosphamide and thiotepa (CY+TT) is particularly toxic to the endothelium, placing patients at elevated risk for TA-TMA.
METHODS
We conducted a retrospective review of pediatric and young adult patients who received conditioned autologous and allogeneic HCT between 2012 and August 2023 at UCSF Benioff Children's Hospital, San Francisco. We excluded patients undergoing gene therapy or triple tandem transplants for brain tumors. Neuroblastoma tandem transplants were classified a single transplant occurrence. High dose N-acetylcysteine (NAC) prophylaxis was incorporated into the institutional standard of care from December 2016-May 2019 and May 2022-August 2023. Defibrotide was given prophylactically to patients deemed high-risk for sinusoidal obstruction syndrome (SOS) per institutional guidelines or on clinical trial NCT#02851407 for SOS prophylaxis or NCT#03384693 for TA-TMA prophylaxis. Kaplan-Meier analysis was used to estimate the 1-year cumulative incidence of TA-TMA. Univariate analysis was performed for each of the potential risk factors of interest using log-rank tests and bivariate analysis with Cox regression models using backward selection and hazard ratios were built using all covariates with a univariate p-value <0.2 for allogeneic HCT. SPSS (v29) was used to estimate all summary statistics, cumulative incidences, and uni- and bi-variate analyses.
RESULTS
A total of 558 transplants were performed with 43 patients developing TA-TMA, for a 1-year cumulative incidence of 8.6% (95% CI, 5.9-11.3%) and 7.2% (95% CI, 2.9-11.5%) in allogeneic and autologous HCTs, respectively (p=0.62). In allogeneic recipients (n=417), the 1-year cumulative incidence of TA-TMA with CY+TT as part of conditioning was 35.7% (95% CI, 15.7-55.7%) compared to 11.7% (95% CI, 7.2-16.2%) with either CY or TT alone, and 1.2% (95% CI, 0-2.8%) if neither agent was included in the conditioning regimen (p<0.001). Use of either CY or TT (HR=10.14; p=0.002) or CY+TT (HR=35.93; p<0.001), viral infections (HR=4.3; p=0.017) and fungal infections (HR=2.98; p=0.027) were significant factors resulting in increased risk for developing TA-TMA. In subjects undergoing autologous HCT (n=141), the 1-year cumulative incidence of TA-TMA with CY+TT was 19.6% (95% CI, 8.8-30.6%) while TA-TMA did not occur in patients receiving either CY or TT alone or when neither were included (p<0.001). TA-TMA occurred only in patients with neuroblastoma receiving CY+TT as part of their conditioning. For autologous patients who received CY+TT, those who were CMV seronegative at the time of HCT had an incidence of TA-TMA of 6.7% (95% CI, 0.1-15.7%) compared to 38.1% (95% CI, 35-41.2%) for those CMV seropositive (p=0.007).
CONCLUSIONS
These data show that CY or TT alone or in combination as part of pre-transplant conditioning prior to HCT increase the incidence of TA-TMA. Alternative conditioning excluding the combination of CY+TT should be considered whenever possible to limit the development of TA-TMA.
PubMed: 38944154
DOI: 10.1016/j.jtct.2024.06.020 -
Journal of Ovarian Research Jun 2024This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests,...
BACKGROUND
This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests, ultrasonographic (US) imaging, and histopathology analysis.
METHODS
Forty-eight rats were divided into six groups (n = 8) as follows: Group A (control) (0.5 mL saline administered intraperitoneally [IP]), Group B (a single 10 mg/kg dose of DOX administered IP on day 1), Group C (a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice), Group D (100 mg/kg of NAC administered IP for 21 days), Group E ( a single 10 mg/kg dose of DOX administered IP on day 1 and 100 mg/kg of NAC administered IP for 21 days), and Group F (100 mg/kg of NAC administered IP for 21 days and a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice). The ovaries were examined using B-mode US on days 1, 14, and 21, and the histopathological examinations of the ovaries and the uterus were undertaken after sacrifice on day 22.
RESULTS
Histomorphological analyses showed that ovarian weight decreased after DOX administration in Group B but not in Group E. US revealed a transient increase in ovarian size in Group B and E, reverting to baseline levels over time, as well as a progressive increase in peritoneal fluid in Groups B and E. Group B exhibited a significant decrease in the thickness of the endometrium and myometrium and uterine cornual length, which was not observed in Group E. Histopathological examination showed that DOX caused a decline in follicular count, especially in primordial, secondary, and Graafian follicles, and resulted in follicular atresia, predominantly in Group B. Destructive degeneration/necrosis and vascular changes were most prominently seen in the corpus luteum of Groups C and B. In NAC-treated rats (Groups E and F), although germ cell damage was present, atretic follicles and vascular changes, such as hyperemia and congestion, were reduced. The anti-müllerian hormone (AMH) level was the highest in Group F.
CONCLUSIONS
NAC, an antioxidant, attenuated DOX-induced gonadotoxicity in rats.
Topics: Animals; Female; Doxorubicin; Acetylcysteine; Rats; Ovary; Ultrasonography; Uterus; Antibiotics, Antineoplastic
PubMed: 38943148
DOI: 10.1186/s13048-024-01459-4 -
Loss of Gcn2 exacerbates gossypol induced oxidative stress, apoptosis and inflammation in zebrafish.Fish & Shellfish Immunology Jun 2024Gossypol, a naturally occurring compound found in cottonseed meal, shows promising therapeutic potential for human diseases. However, within the aquaculture industry, it...
Gossypol, a naturally occurring compound found in cottonseed meal, shows promising therapeutic potential for human diseases. However, within the aquaculture industry, it is considered an antinutritional factor. The incorporation of cottonseed meal into fish feed introduces gossypol, which induces intracellular stresses and hinders overall health of farmed fish. The aim of this study is to determine the role of General control nonderepressible 2 (gcn2), a sensor for intracellular stresses in gossypol-induced stress responses in fish. In the present study, we established two gcn2 knockout zebrafish lines. A feeding trial was conducted to assess the growth-inhibitory effect of gossypol in both wild type and gcn2 knockout zebrafish. The results showed that in the absence of gcn2, zebrafish exhibited increased oxidative stress and apoptosis when exposed to gossypol, resulting in higher mortality rates. In feeding trial, dietary gossypol intensified liver inflammation in gcn2 zebrafish, diminishing their growth and feed conversion. Remarkably, administering the antioxidant N-acetylcysteine (NAC) was effective in reversing the gossypol induced oxidative stress and apoptosis, thereby increasing the gossypol tolerance of gcn2 zebrafish. Exposure to gossypol induces more severe mitochondrial stress in gcn2 zebrafish, thereby inducing metabolic disorders. These results reveal that gcn2 plays a protective role in reducing gossypol-induced oxidative stress and apoptosis, attenuating inflammation responses, and enhancing the survivability of zebrafish in gossypol-challenged conditions. Therefore, maintaining appropriate activation of Gcn2 may be beneficial for fish fed diets containing gossypol.
PubMed: 38936520
DOI: 10.1016/j.fsi.2024.109727 -
Antioxidants (Basel, Switzerland) Jun 2024Skeletal muscle contraction evokes numerous biochemical alterations that underpin exercise benefits. This present study aimed to elucidate the mechanism for electrical...
Skeletal muscle contraction evokes numerous biochemical alterations that underpin exercise benefits. This present study aimed to elucidate the mechanism for electrical pulse stimulation (EPS)-induced antioxidant adaptation in C2C12 myotubes. We found that EPS significantly upregulated Nrf2 and a broad array of downstream antioxidant enzymes involved in multiple antioxidant systems. These effects were completely abolished by pretreatment with a ROS scavenger, N-acetylcysteine. MitoSOX-Red, CM-H2DCFDA, and EPR spectroscopy revealed a significantly higher ROS level in mitochondria and cytosol in EPS cells compared to non-stimulated cells. Seahorse and Oroboros revealed that EPS significantly increased the maximal mitochondrial oxygen consumption rate, along with an upregulated protein expression of mitochondrial complexes I/V, mitofusin-1, and mitochondrial fission factor. A post-stimulation time-course experiment demonstrated that upregulated NQO1 and GSTA2 last at least 24 h following the cessation of EPS, whereas elevated ROS declines immediately. These findings suggest an antioxidant preconditioning effect in the EPS cells. A cell viability study suggested that the EPS cells displayed 11- and 36-fold higher survival rates compared to the control cells in response to 2 and 4 mM HO treatment, respectively. In summary, we found that EPS upregulated a large group of antioxidant enzymes in C2C12 myotubes via a contraction-mitochondrial-ROS-Nrf2 pathway. This antioxidant adaptation protects cells against oxidative stress-associated cytotoxicity.
PubMed: 38929155
DOI: 10.3390/antiox13060716 -
Antioxidants (Basel, Switzerland) May 2024Acetaminophen (APAP) overdose triggers a cascade of intracellular oxidative stress events, culminating in acute liver injury. The clinically used antidote,...
Acetaminophen (APAP) overdose triggers a cascade of intracellular oxidative stress events, culminating in acute liver injury. The clinically used antidote, N-acetylcysteine (NAC), has a narrow therapeutic window, and early treatment is essential for a satisfactory therapeutic outcome. For more versatile therapies that can be effective even at late presentation, the intricacies of APAP-induced hepatotoxicity must be better understood. Accumulation of advanced glycation end products (AGEs) and the consequent activation of the receptor for AGEs (RAGE) are considered one of the key mechanistic features of APAP toxicity. Glyoxalase 1 (Glo-1) regulates AGE formation by limiting the levels of methylglyoxal (MEG). In this study, we studied the relevance of Glo-1 in the APAP-mediated activation of RAGE and downstream cell death cascades. Constitutive Glo-1-knockout mice (GKO) and a cofactor of Glo-1, ψ-GSH, were used as tools. Our findings showed elevated oxidative stress resulting from the activation of RAGE and hepatocyte necrosis through steatosis in GKO mice treated with high-dose APAP compared to wild-type controls. A unique feature of the hepatic necrosis in GKO mice was the appearance of microvesicular steatosis as a result of centrilobular necrosis, rather than the inflammation seen in the wild type. The GSH surrogate and general antioxidant ψ-GSH alleviated APAP toxicity irrespective of the Glo-1 status, suggesting that oxidative stress is the primary driver of APAP toxicity. Overall, the exacerbation of APAP hepatotoxicity in GKO mice suggests the importance of this enzyme system in antioxidant defense against the initial stages of APAP overdose.
PubMed: 38929087
DOI: 10.3390/antiox13060648 -
International Journal of Molecular... Jun 2024Endometriosis in half of affected women is closely related to problems with fertility. Endometriosis-associated infertility is caused by a wide range of abnormalities... (Review)
Review
Endometriosis in half of affected women is closely related to problems with fertility. Endometriosis-associated infertility is caused by a wide range of abnormalities affecting the female reproductive tract, from oocyte quality impairment to disturbances in the eutopic endometrium or mechanical abnormalities resulting from disease progression. Since supportive antioxidant therapies, in addition to surgical treatment or assisted reproductive techniques (ARTs), have overall been proven to be effective tools in endometriosis management, the objective of our review was to analyze the role of antioxidant substances, including vitamins, micronutrients, N-acetylcysteine (NAC), curcumin, melatonin, and resveratrol, in endometriosis-related infertility. Most of these substances have been proven to alleviate the systemic oxidant predominance, which has been expressed through decreased oxidative stress (OS) markers and enhanced antioxidative defense. In addition, we demonstrated that the predominant effect of the aforementioned substances is the inhibition of the development of endometriotic lesions as well as the suppression of pro-inflammatory molecules. Although we can undoubtedly conclude that antioxidants are beneficial in fertility support, further studies explaining the detailed pathways of their action are needed.
Topics: Endometriosis; Humans; Female; Antioxidants; Oxidative Stress; Infertility, Female; Acetylcysteine
PubMed: 38928002
DOI: 10.3390/ijms25126298 -
The Journal of Dermatology Jun 2024Peroxisomal acyl-CoA oxidase 1 (ACOX1), is a peroxisomal enzyme that catalyzes β-oxidation of very-long-chain fatty acids (VLCFA). The gain-of-function variant...
Peroxisomal acyl-CoA oxidase 1 (ACOX1), is a peroxisomal enzyme that catalyzes β-oxidation of very-long-chain fatty acids (VLCFA). The gain-of-function variant p.Asn237Ser in ACOX1 has been shown to cause Mitchell syndrome (MITCH), a neurodegenerative disorder characterized by episodic demyelination, hearing loss, and polyneuropathy, through the overproduction of hydrogen peroxide. Only eight cases of MITCH have been reported. While all these patients experienced cutaneous abnormalities, detailed skin features and potential treatment have not been documented. Herein, we report two MITCH patients who harbored a de novo heterozygous variant p.Asn237Ser in ACOX1 and experienced progressive ichthyosiform erythroderma. Skin histopathology revealed hyperkeratosis and parakeratosis with focal hypogranulosis as well as dyskeratotic keratinocytes. Lipid accumulation in the epidermis was observed using Oil Red O staining. Both patients exhibited a remarkable response to treatment with the topical antioxidant N-acetylcysteine (NAC), with Patient 1 achieving complete recovery after 3 months of consistent treatment. This study provides the first comprehensive description of the clinicopathological characteristics and effective treatment of skin lesions in MITCH patients. The successful treatment with topical NAC suggests excessive reactive oxygen species might play a significant role in the pathogenesis of skin lesions in MITCH.
PubMed: 38923010
DOI: 10.1111/1346-8138.17346 -
La Medicina Del Lavoro Jun 2024In the regeneration of waste oil, a strategical technological process for the European Union circular economy action plan, exhausted oils are regenerated to produce high...
BACKGROUND
In the regeneration of waste oil, a strategical technological process for the European Union circular economy action plan, exhausted oils are regenerated to produce high performing oil bases. Aim of this work was to assess the exposure to benzene in plant workers during ordinary activities.
METHODS
59 workers, potentially exposed to benzene, and 9 administrative workers from an Italian plant were monitored for the whole work shift with personal air samplers; urinary benzene (BEN-U) and S-phenyl mercapturic acid (SPMA) were measured by mass spectrometry methods in end-shift urine samples. Different job tasks were identified among workers.
RESULTS
Median (minimum-maximum) airborne exposures to benzene were <0.9 (<0.9-6.3) and <0.9 (<0.9-0.9) µg/m3, BEN-U and SPMA levels were 0.094 (<0.015-3.095) µg/L and 0.15 (<0.10-9.67) µg/g crt and 0.086 (0.034-0.712) µg/L and <0.10 (<0.10-3.19) µg/g creatinine in workers and administrative workers, respectively. No differences were found among job tasks and between workers and administrative workers, while higher levels were found in smokers than in non-smokers. For all job tasks, the exposure to benzene was always below occupational limit values.
CONCLUSIONS
This study has investigated for the first time the exposure to benzene of workers employed in the re-refining of exhaust oil. The results showed that normal production activities in regenerating used oils do not pose a risk of exposure to benzene in workers.
Topics: Humans; Benzene; Occupational Exposure; Adult; Male; Biological Monitoring; Middle Aged; Air Pollutants, Occupational; Italy; Female; Oil and Gas Industry; Acetylcysteine
PubMed: 38922839
DOI: 10.23749/mdl.v115i3.15863