HDL Function and Atherosclerosis: Reactive Dicarbonyls as Promising Targets of Therapy.

Epidemiologic studies detected an inverse relationship between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major risk factor for ASCVD and suggesting atheroprotective functions of HDL. However, the role of HDL-C as a mediator of risk for ASCVD has been called into question by the failure of HDL-C-raising drugs to reduce cardiovascular events in clinical trials. Progress in understanding the heterogeneous nature of HDL particles in terms of their protein, lipid, and small RNA composition has contributed to the realization that HDL-C levels do not necessarily reflect HDL function. The most examined atheroprotective function of HDL is reverse cholesterol transport, whereby HDL removes cholesterol from plaque macrophage foam cells and delivers it to the liver for processing and excretion into bile. Indeed, in several studies, HDL has shown inverse associations between HDL cholesterol efflux capacity and ASCVD in humans. Inflammation plays a key role in the pathogenesis of atherosclerosis and vulnerable plaque formation, and a fundamental function of HDL is suppression of inflammatory signaling in macrophages and other cells. Oxidation is also a critical process to ASCVD in promoting atherogenic oxidative modifications of LDL (low-density lipoprotein) and cellular inflammation. HDL and its proteins including apoAI (apolipoprotein AI) and PON1 (paraoxonase 1) prevent cellular oxidative stress and LDL modifications. Importantly, HDL in humans with ASCVD is oxidatively modified rendering HDL dysfunctional and proinflammatory. Modification of HDL with reactive carbonyl species, such as malondialdehyde and isolevuglandins, dramatically impairs the antiatherogenic functions of HDL. Importantly, treatment of murine models of atherosclerosis with scavengers of reactive dicarbonyls improves HDL function and reduces systemic inflammation, atherosclerosis development, and features of plaque instability. Here, we discuss the HDL antiatherogenic functions in relation to oxidative modifications and the potential of reactive dicarbonyl scavengers as a therapeutic approach for ASCVD.

Metal-Organic Framework-Based Surface-Enhanced Raman Scattering Sensing Platform for Trace Malondialdehyde Detection in Tears.

Disease biomarkers in tears are crucial for clinical diagnosis and health monitoring. However, the limited volume of tear samples, low concentration of tear biomarkers, and complex tear composition present challenges for precise testing. We introduce a spot-on testing platform of metal-organic framework (MOF)-based surface-enhanced Raman scattering (SERS) capillary column, which is capable of target molecules selective separation and enrichment for tear biomarkers in situ detection. It consists of Au nanostars for effective SERS signal and a porous MOF shell for separating impurities through molecular sieving effect. This platform allows for simultaneous collection and detection of tear, capturing the disease biomarker malondialdehyde in tears with a 9.38 × 10-9 mol/L limit of detection. Moreover, we designed a hand-held device based on this tubular SERS sensor, successfully diagnosing patients with dry eye disease. This functional capillary column enables noninvasive and rapid diagnosis of biomarkers in biofluids, providing potential for disease diagnosis and healthcare monitoring.

Molecular regulators of exercise-mediated insulin sensitivity in non-obese individuals.

Insulin resistance is a significant contributor to the development of type 2 diabetes (T2D) and is associated with obesity, physical inactivity, and low maximal oxygen uptake. While intense and prolonged exercise may have negative effects, physical activity can have a positive influence on cellular metabolism and the immune system. Moderate exercise has been shown to reduce oxidative stress and improve antioxidant status, whereas intense exercise can increase oxidative stress in the short term. The impact of exercise on pro-inflammatory cytokine production is complex and varies depending on intensity and duration. Exercise can also counteract the harmful effects of ageing and inflamm-ageing. This review aims to examine the molecular pathways altered by exercise in non-obese individuals at higher risk of developing T2D, including glucose utilization, lipid metabolism, mitochondrial function, inflammation and oxidative stress, with the potential to improve insulin sensitivity. The focus is on understanding the potential benefits of exercise for improving insulin sensitivity and providing insights for future targeted interventions before onset of disease.

Autoreactive B cells against malondialdehyde-induced protein cross-links are present in the joint, lung, and bone marrow of rheumatoid arthritis patients.

Autoantibodies to malondialdehyde (MDA) proteins constitute a subset of anti-modified protein autoantibodies in rheumatoid arthritis (RA), which is distinct from citrulline reactivity. Serum anti-MDA IgG levels are commonly elevated in RA and correlate with disease activity, CRP, IL6, and TNF-α. MDA is an oxidation-associated reactive aldehyde that together with acetaldehyde mediates formation of various immunogenic amino acid adducts including linear MDA-lysine, fluorescent malondialdehyde acetaldehyde (MAA)-lysine, and intramolecular cross-linking. We used single-cell cloning, generation of recombinant antibodies (n = 356 from 25 donors), and antigen-screening to investigate the presence of class-switched MDA/MAA+ B cells in RA synovium, bone marrow, and bronchoalveolar lavage. Anti-MDA/MAA+ B cells were found in bone marrow plasma cells of late disease and in the lung of both early disease and risk-individuals and in different B cell subsets (memory, double negative B cells). These were compared with previously identified anti-MDA/MAA from synovial memory and plasma cells. Seven out of eight clones carried somatic hypermutations and all bound MDA/MAA-lysine independently of protein backbone. However, clones with somatic hypermutations targeted MAA cross-linked structures rather than MDA- or MAA-hapten, while the germline-encoded synovial clone instead bound linear MDA-lysine in proteins and peptides. Binding patterns were maintained in germline converted clones. Affinity purification of polyclonal anti-MDA/MAA from patient serum revealed higher proportion of anti-MAA versus anti-MDA compared to healthy controls. In conclusion, IgG anti-MDA/MAA show distinct targeting of different molecular structures. Anti-MAA IgG has been shown to promote bone loss and osteoclastogenesis in vivo and may contribute to RA pathogenesis.

Investigation of genetic diversity using molecular and biochemical markers associated with powdery mildew resistance in different flax (Linum usitatissimum L.) genotypes.

Under greenhouse conditions, the resistance of 18 different genotypes of flax to powdery mildew was evaluated. To investigate genetic diversity and identify the molecular and biochemical markers linked to powdery mildew resistance in the tested genotypes, two molecular marker systems-start codon targeted (SCoT) and inter-simple sequence repeat (ISSR)-as well as a biochemical marker (protein profiles, antioxidant enzyme activity, and secondary metabolites) were used. Based on the results, the genotypes were classified into four categories: highly susceptible, susceptible, moderately susceptible, and moderately resistant. The genotypes differed significantly in powdery mildew severity: Polk had a severity of 92.03% and Leona had a severity of 18.10%. Compared to the other genotypes, the moderately resistant genotypes had higher levels of flavonoids, antioxidant enzymes, phenolics, and straw yield; nevertheless, their hydrogen peroxide and malondialdehyde levels were lower. Protein profiles revealed 93.75% polymorphism, although the ISSR marker displayed more polymorphism (78.4%) than the SCoT marker (59.7%). Specific molecular and biochemical markers associated with powdery mildew resistance were identified. The 18 genotypes of flax were divided into two major clusters by the dendrogram based on the combined data of molecular markers. The first main cluster included Leona (genotype number 7), considered moderate resistance to powdery mildew and a separate phenetic line. The second main cluster included the other 17 genotypes, which are grouped together in a sub-cluster. This means that, besides SCoT, ISSR markers can be a useful supplementary technique for molecular flax characterization and for identifying genetic associations between flax genotypes under powdery mildew infection.

Predicting and optimizing reactive oxygen species metabolism in Punica granatum L. through machine learning: role of exogenous GABA on antioxidant enzyme activity under drought and salinity stress.

BACKGROUND: Drought and salinity stress have been proposed as the main environmental factors threatening food security, as they adversely affect crops' agricultural productivity. As a potential solution, the application of plant growth regulators to enhance drought and salinity tolerance has gained considerable attention. γ-aminobutyric acid (GABA) is a four-carbon non-protein amino acid that accumulates in plants as a response to stressful conditions. This study focused on a comparative assessment of several machine learning (ML) regression models, including radial basis function, generalized regression neural network (GRNN), random forest (RF), and support vector regression (SVR) to develop predictive models for assessing the effect of different concentrations of GABA (0, 10, 20, and 40 mM) on various physio-biochemical traits during periods of drought, salinity, and combined stress conditions. The physio-biochemical traits included antioxidant enzyme activities (superoxide dismutase, SOD; peroxidase, POD; catalase, CAT; and ascorbate peroxidase, APX), protein content, malondialdehyde (MDA) levels, and hydrogen peroxide (H2O2) levels. The non­dominated sorting genetic algorithm­II (NSGA­II) was employed for optimizing the superior prediction model. RESULTS: The GRNN model outperformed the other ML algorithms and was therefore selected for optimization by NSGA-II. The GRNN-NSGA-II model revealed that treatment with GABA at concentrations of 20.90 mM and 20.54 mM, under combined drought and salinity stress conditions at 20.86 and 20.72 days post-treatment, respectively, could result in the maximum values for protein content (by 0.80 and 0.69), APX activity (by 50.63 and 51.51), SOD activity (by 0.54 and 0.53), POD activity (by 1.53 and 1.72), CAT activity (by 4.42 and 5.66), as well as lower MDA levels (by 0.12 and 0.15) and H2O2 levels (by 0.44 and 0.55), respectively, in the 'Atabaki' and 'Rabab' cultivars. CONCLUSIONS: This study demonstrates that the GRNN-NSGA-II model, as an advanced ML algorithm with a strong predictive ability for outcomes in combined stressful environmental conditions, provides valuable insights into the significant factors influencing such multifactorial processes.

Oxidative modification of collagen by malondialdehyde in porcine skin.

Human skin is exposed to various physical and chemical stress factors, which commonly cause the oxidation of lipids and proteins. In this study, azo initiator AAPH [2,2' -azobis(2-methylpropionamidine) dihydrochloride] was employed to initiate lipid peroxidation in porcine skin as an ex vivo model for human skin. We demonstrate that malondialdehyde (MDA), a secondary product of lipid peroxidation, is covalently bound to collagen in the dermis, forming MDA-collagen adducts. The binding of MDA to collagen results in an unfolding of the collagen triple helix, formation of the dimer of α-chains of collagen, and fragmentation of the collagen α-chain. It is proposed here that the MDA is bound to the lysine residues of α-chain collagen, which are involved in electrostatic interaction and hydrogen bonding with the glutamate and aspartate of other α-chains of the triple helix. Our data provide crucial information about the MDA binding topology in the skin, which is necessary to understand better the various types of skin-related diseases and the aging process in the skin under stress.

Impact of a 50bp insertion/deletion polymorphism of the superoxide dismutase-1 on oxidative stress status and risk of keratoconus.

Keratoconus (KC) is characterized by the predominant primary ectatic disease, affecting the cornea, necessitating corneal transplants in some cases. While some loci associated with KC risk have been identified, the understanding of the disease remains limited. Superoxide dismutase (SOD) enzymes play a crucial role in countering the reactive oxygen species and providing protection against oxidative stress (OS). Accordingly, the objective of this study was to investigate a potential association of a 50 nucleotide base pairs (bp) insertion/deletion (I/D) within the SOD1 promoter, and the located 1684 bp upstream of the SOD1 ATG, with KC in the Iranian population. Additionally, an assessment was conducted on SOD activity and the total antioxidant capacity (TAC), as determined by the ferric reducing-antioxidant power assay, along with malondialdehyde (MDA) levels. In this case-control study, genomic DNA was extracted from the blood cells of KC (n = 402) and healthy (n = 331) individuals. The genotype of this gene was determined using the PCR technique. Furthermore, the amount of SOD enzyme activity and the MDA and TAC levels were measured in the serum of the study groups. The (I/I) genotype was present in 84.23%, the (I/D) genotype in 15.06%, and the (D/D) genotype in 0.69% of both groups. A statistically significant relationship was seen between different genotypes and TAC, MDA, and SOD1 activity indices (P < 0.05). Individuals with the D/D genotype exhibited a decrease in total antioxidant capacity, an increase in the amount of MDA, and a decrease in SOD1 enzyme activity (P < 0.05). Moreover, the logistic regression analysis of KC development indicated that elevated levels of MDA increased the risk of KC incidence in the patient group compared to the healthy group, while a higher activity of SOD1 and greater values of TAC decreased the KC risk. The removal of the 50 bp fragment reduced SOD1 activity and elevated OS levels, thereby impacting the oxidant-antioxidant balance. This could potentially play a significant role in individuals afflicted by KC.

Severity of Mitral Valve Stenosis　- Possible Relationships With Blood Oxidant Markers and Antioxidants.

BACKGROUND: This study examined whether the severity of mitral valve stenosis (MVS) is associated with oxidative stress (OS) markers in the blood, and other hematological and clinicodemographic parameters.Methods and Results: This prospective study was conducted between March and May 2022. Seventy-five patients with newly diagnosed MVS (25 mild, 25 moderate, 25 severe) were included. Mild, moderate, and severe MVS was defined as MV area >2, 1.5-2, and <1.5 cm2, respectively. Various OS markers and laboratory parameters were determined in venous blood samples. For predictive analyses, 2 different analyses were performed to detect patients with severe MVS and those with moderate or severe (moderate/severe) MVS. Age (P=0.388) and sex (P=0.372) distribution were similar in the 3 groups. Multiple logistic regression analysis revealed that a high white blood cell (WBC) count (P=0.023) and high malondialdehyde (P=0.010), superoxide dismutase (SOD; P=0.008), and advanced oxidation protein products (AOPP; P=0.007) levels were independently associated with severe MVS. A low platelet count (P=0.030) and high malondialdehyde (P=0.018), SOD (P=0.008), and AOPP (P=0.001) levels were independently associated with having moderate/severe MVS. The best discriminatory factors for severe MVS were SOD (cut-off >315.5 ng/mL) and glutathione (cut-off >4.7 µmol/L). CONCLUSIONS: MVS severity seems to be affected by oxidant markers (malondialdehyde and AOPP), antioxidant enzymes (SOD), and inflammation-related cells (WBC and platelets). Future studies are needed to examine these relationships in larger populations.

Naturalistic comparison of clomethiazole and Diazepam treatment in alcohol withdrawal: effects on oxidative stress, inflammatory cytokines and hepatic biomarkers.

Ethanol is metabolized by alcohol dehydrogenase to acetaldehyde and induces cytochrome P450 2E1 (CYP2E1), which generates reactive oxygen species that cause inflammatory liver damage. Clomethiazole, a drug approved for alcohol withdrawal treatment (AWT) in some European countries, inhibits CYP2E1. We hypothesized that clomethiazole would lead to a faster reduction in oxidative stress, inflammatory cytokines, and liver enzymes compared to diazepam treatment. We analysed respective biomarkers in 50 patients undergoing AWT and 25 healthy individuals but found no statistical difference between the two medication groups over 3-5 days. Hence, our hypothesis was not confirmed during this observation period.

Exploring bioluminescence in Aglaonema: Investigating Vibrio campbellii translocation and plant responses under CaCl2 stimulation.

The feasibility of creating light-emitting plants by immobilizing Vibrio campbellii RMT1 on the rhizospheric zone of Aglaonema sp. 'Banlangngoen' was investigated in depth, including bacteria translocation and plant response. Results from scanning electron microscope showed that an inorganic salt-containing medium affected the root. However, transmission electron microscope results displayed bacteria translocation through the root to the leaf and colonized in the cytosol of vascular tissues. Bacteria cell counts exhibited high colonization in the root zone, approximately 3.65 × 106 CFU/mL, resulting in a light-emitting intensity increase of 23.68-fold higher than the control after the first week. Nevertheless, light microscope revealed that inorganic salts in the culture medium led to enlarged air spaces, resulting in leaf and stalk withering. Notably, spraying plants with calcium chloride (CaCl2) solution effectively mitigated salt stress, activated luminescence, and facilitated bacterial movement from roots to leaves. Additionally, CaCl2 contributed to ongoing salinity reduction in the culture medium, as evidenced by reduced malondialdehyde levels, alongside increased indole-3-acetic acid and salicylic acid concentrations, indicating plant defense responses. The interaction between plants and luminescent bacteria demonstrated the potential for producing glowing plants following CaCl2 application, addressing salinity stress, enhancing luminescence, and maintaining plant growth.

Adjunctive silymarin supplementation and its effects on disease severity, oxidative stress, and inflammation in patients with Alzheimer's disease.

BACKGROUND: Brain tissue in Alzheimer's patients is exposed to oxidative stress. Silymarin is an adjunct drug that has anti-inflammatory and antioxidant properties. OBJECTIVE: This study aimed to evaluate the effect of silymarin on biomarkers of oxidative stress, inflammation, and disease severity in Alzheimer's patients. METHODS: This randomized, single-blind clinical trial study was performed on 33 patients with Alzheimer's disease (AD) whose disease was confirmed by DSM-5 criteria and by brain imaging. Patients in the case group received three 250 mg silymarin capsules daily (each containing 150 mg silymarin), as an adjunctive medication in addition to the routine medication regimen. In the placebo group (control), patients received the same amount of placebo. All patients underwent Mini Mental State Exam (MMSE) and a panel of blood tests including malondialdehyde, neopterin, catalase, paraoxonase-1, total oxidative status, and total antioxidant capacity to reevaluate the changes pre/postintervention at the end of the trimester. RESULTS: The catalase and MDA serum levels after the adjunctive silymarin treatment decreased significantly (Catalasebefore silymarin = 9.29 ± 7.02 vs Catalaseafter silymarin = 5.32 ± 2.97, p = 0.007 and MDAbefore silymarin = 4.29 ± 1.90 vs MDAafter silymarin = 1.66 ± 0.84, p < 0.001) while MMSE increased notably (MMSEbefore silymarin = 10.39 ± 6.42 vs MMSEafter silymarin = 13.37 ± 6.81, p < 0.001). CONCLUSION: Silymarin can be effective as an adjunct drug and a powerful antioxidant in reducing oxidative stress and improving the course of AD.

Hydrogen sulfide regulates arsenic-induced cell death in yeast cells by modulating the antioxidative system.

Arsenic (As) is a metal with potentially toxic effects on different organisms. Hydrogen sulfide (H2S) plays a vital role in mitigating heavy metal toxicity by reducing oxidative stress in plants and animals. However, the role of H2S in alleviating arsenic toxicity in yeast cells remains unclear. In this study, the role of NaHS (exogenous physiological H2S) in alleviating As-induced yeast cell death was investigated. Yeast cells in the logarithmic phase were pretreated with 0.05 mmol/L NaHS for 6 h, and then incubated in the YPD medium with or without 1 mmol/L As. After 12 h of treatment, relative survival rate, H2S content, oxidative stress biomarkers, and antioxidant machinery were measured. Our results showed that sodium arsenite-induced yeast cell death and pretreatment with 0.05 mmol/L NaHS significantly alleviated sodium arsenite-induced cell death. Under sodium arsenite conditions, the levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) increased, accompanied by the inhibition of the catalase (CAT) activity and the downregulation of CTT1 expression. However, the activities of the superoxide dismutase (SOD) and glutathion peroxidase (GPX) increased, and the expression of SOD1 and GPX2 was markedly upregulated in the group treated with sodium arsenite. When yeast cells were pretreated with NaHS, the intracellular ROS and MDA levels decreased significantly, and the activities of SOD, CAT, and GPX increased significantly. This was associated with a significant increase in relative survival rate and H2S content compared to the arsenic treatment alone. Our findings indicate that NaHS alleviates sodium arsenite-induced yeast cell death, mainly by enhancing the antioxidant defense system.

Metarhabditis amsactae: A potential biopesticide isolated from Punjab (India) with potent insecticidal activity and immunomodulatory effects against Galleria mellonella (Lepidoptera: Pyralidae).

A survey was undertaken to isolate entomopathogenic nematodes from Amritsar district of Punjab, India. Out of 20 soil samples collected, two were found positive for the presence of nematodes. 18S and ITS rDNA gene sequencing revealed their identity as Metarhabditis amsactae. To assess its biocontrol potential, Galleria mellonella larvae were treated with concentrations of 20, 40, 80 and 160 IJs/L (infective juveniles/larva) and mortality was recorded from 24 h up to 96 h of nematode exposure. Distilled water without nematodes was used as an untreated control. M. amsactae showed potent larvicidal activity against G. mellonella that was found to be concentration and time dependent. Nematode infection caused 93.33 % larval mortality at 80 IJs/L after 72 h of treatment. 100 % mortality was observed after 96 h. No mortality was observed in control. To evaluate the immunomodulatory effects of M. amsactae, G. mellonella larvae were infected with 100 IJs/L and activities of antioxidant and detoxifying enzymes viz., superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APOX), phenol oxidase (PO), glutathione-S-transferase (GST) and acetylcholine esterase (AChE) were appraised after 12, 24, 36 and 48 h of nematode exposure. Malondialdehyde content was also determined. The results obtained demonstrated a significant elevation in all the enzyme activities at all time intervals in treated larvae when compared with untreated control. MDA levels were also enhanced in response to nematode infection. Thus, the present study revealed high insecticidal potential and immunomodulatory effects of M. amsactae on G. mellonella that should be further explored on other insect pests as well.

Effects of Silver Nanoparticles on the Red Microalga Porphyridium purpureum CNMN-AR-02, Cultivated on Two Nutrient Media.

The purpose of this study was to examine the influence of 10 and 20 nm nanoparticles (AgNPs) on the growth and biochemical composition of microalga Porphyridium purpureum CNMN-AR-02 in two media which differ by the total amount of mineral salts (MM1 with 33.02 g/L and MM2 with 21.65 g/L). Spectrophotometric methods were used to estimate the amount of biomass and its biochemical composition. This study provides evidence of both stimulatory and inhibitory effects of AgNPs on different parameters depending on the concentration, size, and composition of the nutrient medium. In relation to the mineral medium, AgNPs exhibited various effects on the content of proteins (an increase up to 20.5% in MM2 and a decrease up to 36.8% in MM1), carbohydrates (a decrease up to 35.8% in MM1 and 39.6% in MM2), phycobiliproteins (an increase up to 15.7% in MM2 and 56.8% in MM1), lipids (an increase up to 197% in MM1 and no changes found in MM2), antioxidant activity (a decrease in both media). The composition of the cultivation medium has been revealed as one of the factors influencing the involvement of nanoparticles in the biosynthetic activity of microalgae.

The efficacy of curcumin supplementation on serum total antioxidant capacity, malondialdehyde, and disease activity in women with rheumatoid arthritis: A randomized, double-blind, placebo-controlled clinical trial.

Oxidative stress plays a crucial role in the physiopathology of rheumatoid arthritis (RA), which is associated with impaired antioxidant defenses. This study aimed to investigate the effects of curcumin supplementation on serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), and disease activity in women with RA. In this clinical trial, 48 women with RA were treated with one capsule of curcumin (500 mg daily) or placebo for 8 weeks. Anthropometric measurements and fasting blood samples were collected at baseline and end of the study. Finally, we assessed the Disease Activity Score in 28 joints (DAS-28), dietary intake, and physical activity levels. While curcumin supplementation for 8 weeks significantly increased the serum levels of TAC (p < 0.05), it decreased tender joint counts, swollen joint counts, visual analog scale (VAS) for pain, and DAS-28 compared to the placebo at the end of the study (p < 0.001 for all). MDA levels significantly decreased in the curcumin group (p < 0.05). However, changes in MDA concentration were not significant between groups at the end of the trial (p = 0.145). Curcumin supplementation had a beneficial effect on increasing the serum levels of TAC and decreased DAS-28 in women with RA.

Click evoked otoacoustic emissions in occupational exposure to lead, concentrations of selected essential elements and markers of oxidative stress.

PURPOSE: This study focused on the selected markers of oxidative stress, impact of elevated lead levels on long-term hearing quality. We investigated whether the presence of certain essential minerals might provide protection to the auditory system against the effects of lead (and cadmium) compounds. METHODS: The research group included 280 male employees of the zinc and lead smelter, which was divided into: L-Pb-low blood lead concentration (PbB) subgroup, H-Pb-high PbB subgroup. Hearing tests were performed using the click evoked otoacoustic emission (CEOAE). RESULTS: Zinc protoporphyrin level was significantly higher in the H-Pb subgroup by 68%. Cd concentration was significantly higher in H-Pb by 33%. The Ca concentration was significantly lower in the H-Pb by - 2%. Selected oxidative stress markers concentration were significantly higher in the H-Pb group: malondialdehyde (MDA) by 4%, and lipofuscin (LPS) by 9%. In the CEOAE results showed statistically significant differences between the L-Pb and H-Pb subgroups. Larger negative changes in otoemission amplitude were observed in H-Pb subgroup. All otoemission results showed a statistically significant negative correlation with age, time of work, MDA concentration, and with PbB. Selected CEOAE parameters showed a significant negative correlation with cadmium blood concentration (CdB), and a positive correlation with Ca and Zn. CONCLUSION: Elevated blood lead content in occupational exposure is associated with an increase in MDA and LPS concentration, which negatively correlates with CEOAE parameters. This suggests an important role of oxidative stress in the long-term deterioration of hearing.

Effects of topical ketorolac tromethamine on tear parameters, meibography, goblet cell density, and conjunctival oxidative stress in healthy dogs.

OBJECTIVES: The objective of the study was to evaluate whether a twice-daily instillation of 0.45% preservative-free ketorolac tromethamine (FKT) or 0.4% benzalkonium chloride-preserved ketorolac tromethamine (BACKT), every 12 h for 30 days may affect tear film parameters and the meibography in healthy dogs. Additionally, we assessed whether the same treatments irritated the ocular surface, affected goblet cell density (GCD), and the levels of oxidative stress biomarkers (OSB) in the conjunctiva of the same dogs. PROCEDURES: Experimental and masked comparison study. In 11 healthy dogs baseline values of the lipid layer thickness, tear meniscus height, non-invasive tear breakup time (NI-TFBT), and the meibomian gland (MG) loss were assessed by OSAvet®. For each dog, one eye received 40 µL of BACKT, while the other received 40 µL FKT, every 12 h for 30 consecutive days. Tear parameters and meibography were repeated 15, 30, and 60 days post-treatments. Conjunctival hyperemia and blepharospasm were monitored at the same time points. At baseline and Day 30, a conjunctival biopsy was collected for GCD and OSB determination. RESULTS: Conjunctival hyperemia and blepharospasm were not observed. At Day 15, the MG loss increased only in FKT-treated eyes (p < .001). On Day 30, both treatment groups showed increased MG loss, shortened NI-TFBT, and reduced GCD and catalase (p < .05). At Day 30, BACKT-treated eyes showed lower levels of superoxide dismutase (SOD) (p = .006) and higher levels of malondialdehyde (MDA) (p = .02). Differences between treatments were not observed for any parameter at any time point (p > .05). 60 days after treatment, OSAvet® parameters tended to return to values assessed at baseline; however, significant differences remained for MG loss (p < .05). CONCLUSIONS: Twice-daily instillation of KT, containing or not BAC, for 30 consecutive days shortened NI-TFBT, decreased GCD, and increased the MG loss in healthy dogs. KT should be used with caution when prescribed for long periods, particularly in patients with tear film abnormalities. However, future controlled studies using KT, BAC, and other topical NSAIDs are indicated to further support this finding.

Male reproductive hormone disorders among copper smelter workers.

Male workers in copper smelting are exposed to copper, lead, and arsenic. This study aimed to assess the effects of combined exposure to these metals on male reproductive hormone levels and assesses malondialdehyde (MDA) as an oxidative stress parameter. The study was conducted on 40 copper smelter workers compared with 40 non-exposed workers. Laboratory investigations included levels of serum copper, blood lead, serum arsenic, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and MDA. Levels of copper, arsenic, lead, FSH, and LH were significantly increased compared to controls. However, a statistically significant decrease in the mean value of testosterone was found among exposed workers. Positive correlations between serum copper and both serum FSH and MDA levels were statistically significant as were correlations between serum arsenic and MDA levels. Testosterone levels showed significant negative correlations with both copper and arsenic among exposed workers. A linear regression model of copper, arsenic, and lead levels as independent variables with FSH, LH, and testosterone as dependent variables revealed a significant negative association between serum copper and testosterone levels. The current study concluded that combined exposure to copper, arsenic, and lead in secondary copper smelters had a negative impact on male reproductive hormone levels that may be mediated by oxidative stress.

Relationship between phthalates exposure, risk of decreased ovarian reserve, and oxidative stress levels.

Phthalates (PAEs), a group of environmental endocrine disruptors, are associated with oxidative stress and have adverse effects on female ovarian reserves. However, this association has been poorly investigated, particularly with respect to clinical evidence. In this study, we provided clinical evidence of a relationship between exposure levels of PAEs, oxidative stress and decreased ovarian reserve (DOR). Firstly, the urinary concentrations of metabolites of PAEs were measured by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), and the biomarkers of oxidative stress, malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), were determined. Finally, statistical analyses were conducted to describe the relationship between the PAEs exposure, oxidative stress and DOR. We found that the levels of monomethyl phthalate (MMP), monoisobutyl phthalate (MiBP), mono-(2-ethylhexyl) phthalate (MEHP), and mono-(2-ethyl-5-hydroxypentyl) phthalate (MECPP) in the DOR group were significantly higher than those in the control group. There was a significant negative association between AMH and MMP, MiBP levels. and a significant positive association between FSH and MMP levels. PAEs exposure was also associated with a significant increase in MDA levels and decrease in SOD levels. In conclusion, the exposure of PAEs was closely associated with DOR, potentially mediated by oxidative stress pathways; however, small sample size was a limitation in this study.