Decreased Antioxidant Levels Research Articles

Oxidative Stress-induced Hormonal Disruption in Male Reproduction.

Research into the impacts of oxidative stress (OS), and hormonal balance on reproductive potential has increased over the last 40 years possibly due to rising male infertility. Decreased antioxidant levels and increased OS in tissues result from hormonal imbalance, which in turn leads to male infertility. Increased reactive oxygen species (ROS) generation in seminal plasma has been linked to many lifestyle factors such as alcohol and tobacco use, toxicant exposure, obesity, varicocele, stress, and aging. This article provides an overview of the crosslink between OS and gonadal hormone disruption, as well as a potential mode of action in male infertility. Disrupting the equilibrium between ROS generation and the antioxidant defense mechanism in the male reproductive system may affect key hormonal regulators of male reproductive activities. Unchecked ROS production may cause direct injury on reproductive tissues or could disrupt normal regulatory mechanisms of the hypothalamic-pituitary-gonadal (HPG) axis and its interaction with other endocrine axes, both of which have negative effects on male reproductive health and can lead to male infertility.

Comparative Study of Antioxidant Activity of Dextran-Coated Iron Oxide, Gold, and Silver Nanoparticles Against Age-Induced Oxidative Stress in Erythrocytes.

Erythrocytes undergo several changes during human aging and age-related diseases and, thus, have been studied as biomarkers of the aging process. The present study aimed to explore the antioxidant ability of metal and metal oxide nanoparticles (NPs) such as iron oxide (Fe3O4), gold (Au), and silver (Ag) to mitigate age-related oxidative stress in human erythrocytes. Metal and metal oxide NPs behave like antioxidative enzymes, directly influencing redox pathways and thus have better efficiency. Additionally, biopolymer coatings such as dextran enhance the biocompatibility of these NPs. Therefore, dextran-coated Fe3O4, Au, and Ag NPs were synthesized using wet chemical methods and were characterized. Their hemocompatibility and ability to protect erythrocytes from age-induced oxidative stress were investigated. The Fe3O4 and Au NPs were observed to protect erythrocytes from hydrogen peroxide and age-induced oxidative damage, including decreased antioxidant levels, reduced activity of antioxidative enzymes, and increased amounts of oxidative species. Pretreatment with NPs preserved the morphology and membrane integrity of the erythrocyte. However, Ag NPs induced oxidative stress in erythrocytes similar to hydrogen peroxide. Therefore, dextran-coated Fe3O4 and Au nanoparticles have the potential to be employed as antioxidant therapies against age-related oxidative stress.

Effect of Ferulic Acid Loaded in Nanoparticle on Tissue Transglutaminase Expression Levels in Human Glioblastoma Cell Line.

Glioblastoma (GBM) is one of the most aggressive cancers, characterized by a decrease in antioxidant levels. Evidence has demonstrated that ferulic acid (FA), a natural antioxidant particularly abundant in vegetables and fruits, could be a promising candidate for GBM treatment. Since FA shows a high instability that compromises its therapeutic application, it has been encapsulated into Nanostructured Lipid Carriers (NLCs) to improve its bioavailability in the brain. It has been demonstrated that tissue transglutaminase (TG2) is a multi-functional protein implicated in many physiological and pathological processes, including cancer. TG2 is also involved in GBM correlated with metastasis formation and drug resistance. Therefore, the evaluation of TG2 expression levels and its cellular localization are important to assess the anti-cancer effect of FA against GBM cancer. Our results have demonstrated that treatment with free FA and FA-NLCs in the U87-MG cancer cell line differently modified TG2 localization and expression levels. In the cells treated with free FA, TG2 appeared expressed both in the cytosol and in the nucleus, while the treatment with FA-NLCs showed that the protein is exclusively localized in the cytosol, exerting its pro-apoptotic effect. Therefore, our data suggest that FA loaded in NLCs could represent a promising natural agent for supplementing the current anti-cancer drugs used for the treatment of GBM.

Zinc oxide nanoparticles derived from Penicillium griseofulvum mitigate DMBA/TPA-promoted mice skin carcinogenesis by modulating NF-ĸB associated signalling.

This study investigates the synthesis of zinc oxide nanoparticles using Penicillium griseofulvum (ZnONPs-PG) and their potential role in preventing DMBA/TPA-induced skin cancer. The synthesis process involved using a 1-mM zinc acetate dihydrate as a precursor in P. griseofulvum. Various analytical techniques, including FTIR spectroscopy, UV-Vis, TEM, XRD, and DLS, were utilized to characterize the ZnONPs. The efficacy of ZnONPs-PG was then evaluated in a DMBA/TPA-induced skin cancer model. Mice were treated topically with DMBA/TPA in acetone (200μL) over 2weeks, with treatments continuing for 20weeks. Results showed 100% tumor occurrence, histological changes, elevated lipid peroxidation (LPO) levels, and decreased antioxidant levels in DMBA/TPA-treated mice. However, topical application of ZnONPs magnificently reverted the tumor occurrence, histological changes, elevated malanoldehyde and hydrogen peroxide levels; decreased antioxidant levels in DMBA/TPA-treated mice. ZnONPs-PG treatment suppressed the increased levels of inflammatory markers (COX-2, iNOS and NF-κB,) and cell proliferation markers (Cyclin-E1, Cyclin D1, VEGF, TGF-β1) exposed mice. In addition, ZnONPs-PG treatment decreased the DMBA/TPA-induced anti-apoptotic Bcl-2 protein and increasing the expression of pro-apoptotic markers (Bax and caspase 3) in skin tissues. Thus, ZnONPs-PG may prevent skin carcinogenesis through its potent antioxidant properties and inhibiting NF-κB-mediated inflammatory and proliferation pathways.

The bacterial metabolite, lithocholic acid, has antineoplastic effects in pancreatic adenocarcinoma

Lithocholic acid (LCA) is a secondary bile acid. LCA enters the circulation after bacterial synthesis in the gastrointestinal tract, reaches distantly located cancer cells, and influences their behavior. LCA was considered carcinogenic, but recent studies demonstrated that LCA has antitumor effects. We assessed the possible role of LCA in pancreatic adenocarcinoma. At the serum reference concentration, LCA induced a multi-pronged antineoplastic program in pancreatic adenocarcinoma cells. LCA inhibited cancer cell proliferation and induced mesenchymal-to-epithelial (MET) transition that reduced cell invasion capacity. LCA induced oxidative/nitrosative stress by decreasing the expression of nuclear factor, erythroid 2-like 2 (NRF2) and inducing inducible nitric oxide synthase (iNOS). The oxidative/nitrosative stress increased protein nitration and lipid peroxidation. Suppression of oxidative stress by glutathione (GSH) or pegylated catalase (pegCAT) blunted LCA-induced MET. Antioxidant genes were overexpressed in pancreatic adenocarcinoma and decreased antioxidant levels correlated with better survival of pancreatic adenocarcinoma patients. Furthermore, LCA treatment decreased the proportions of cancer stem cells. Finally, LCA induced total and ATP-linked mitochondrial oxidation and fatty acid oxidation. LCA exerted effects through the farnesoid X receptor (FXR), vitamin D receptor (VDR), and constitutive androstane receptor (CAR). LCA did not interfere with cytostatic agents used in the chemotherapy of pancreatic adenocarcinoma. Taken together, LCA is a non-toxic compound and has antineoplastic effects in pancreatic adenocarcinoma.

Nuclear Factor Erythroid 2-Related Factor 2 as a Potential Therapeutic Target in Neonatal Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a prominent cause of neonatal mortality and neurodevelopmental disorders; however, effective therapeutic interventions remain limited. During neonatal hypoxic-ischemic injury events, increased reactive oxygen species (ROS) production and decreased antioxidant levels lead to the induction of oxidative stress, which plays a pivotal role in the pathological process of neonatal HIE. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key endogenous antioxidant transcription factor that protects against oxidative stress by promoting the transcription of various antioxidant genes. It has been demonstrated that Nrf2 signaling pathway activation by different compounds may protect against neonatal HIE. This review outlines the role of oxidative stress in neonatal HIE and summarizes the impact of antioxidants on neonatal HIE via activation of the Nrf2 signaling pathway. In conclusion, Nrf2 signaling pathway potentially exerts antioxidant, anti-inflammatory, antiapoptotic and antiferroptotic effects, thereby emerging as a focal point for future neonatal HIE treatment strategies.

Effects of antioxidant supplementation for polycystic ovary syndrome

Introduction and purpose: Polycystic ovary syndrome is the most common endocrinopathy in women, with a prevalence ranging from 10% to 13%. Oxidative stress and decreased antioxidant levels contribute to the development of various diseases, and one of them is polycystic ovary syndrome. The aim of this review is to provide an overview of the current knowledge about the effects of antioxidant administration in PCOS treatment. A brief description of the state of knowledge: Oxidative stress is an imbalance between increased levels of reactive oxygen species and a decreased efficiency of antioxidant mechanisms, which can potentially cause damage. The harmful effects of free radicals might be neutralized by antioxidants obtained from the diet, such as polyphenols, vitamins C, and E. These compounds improve several aspects of the PCOS pathomechanism, including hormonal imbalance, glucose metabolism, lipid profile, and ovarian functionality. Conclusions: The outcomes of all the reviewed studies in this paper indicate that antioxidants such as resveratrol, curcumin, vitamin C and E, N-acetylcysteine, and melatonin have therapeutic potential in the management of PCOS. However, currently antioxidant therapies cannot be recommended in PCOS therapy since there is a need for more prospective randomized clinical trials on a larger sample to establish a long-term effects of antioxidants supplementation in PCOS, the optimal dosage, and finally to assess which antioxidant is the most efficient in PCOS treatment.

Effects of antioxidant supplementation for polycystic ovary syndrome

Introduction and purpose: Polycystic ovary syndrome is the most common endocrinopathy in women, with a prevalence ranging from 10% to 13%. Oxidative stress and decreased antioxidant levels contribute to the development of various diseases, and one of them is polycystic ovary syndrome. The aim of this review is to provide an overview of the current knowledge about the effects of antioxidant administration in PCOS treatment. A brief description of the state of knowledge: Oxidative stress is an imbalance between increased levels of reactive oxygen species and a decreased efficiency of antioxidant mechanisms, which can potentially cause damage. The harmful effects of free radicals might be neutralized by antioxidants obtained from the diet, such as polyphenols, vitamins C, and E. These compounds improve several aspects of the PCOS pathomechanism, including hormonal imbalance, glucose metabolism, lipid profile, and ovarian functionality. Conclusions: The outcomes of all the reviewed studies in this paper indicate that antioxidants such as resveratrol, curcumin, vitamin C and E, N-acetylcysteine, and melatonin have therapeutic potential in the management of PCOS. However, currently antioxidant therapies cannot be recommended in PCOS therapy since there is a need for more prospective randomized clinical trials on a larger sample to establish a long-term effects of antioxidants supplementation in PCOS, the optimal dosage, and finally to assess which antioxidant is the most efficient in PCOS treatment.

Predictive effect of thiol/disulfide homeostasis dynamics on early pregnancy viability: A case-control study.

The main aim of this study was to investigate the differences in maternal serum thiol/disulfide homeostasis among women with abortion imminens (AI), missed abortion (MA), and healthy pregnancies during the first trimester. This was a prospective case-control study. This study was conducted on pregnant women who visited the Obstetrics Clinic at University of Health Sciences Turkey, Etlik Zübeyde Hanım Gynecology Training and Research Hospital and were diagnosed with either AI or MA during the 6th to 14th weeks of pregnancy. The participants had a normal pregnancy follow-up, no chronic illnesses, and did not take any multivitamin or antioxidant supplements except for folic acid. The study incorporated 33 pregnant women with AI, 36 with MA, and 40 with normal pregnancies. Age, and body mass index were matched across the three groups. This study used a recently developed automated spectrophotometric technique to quantify thiol/disulfide concentrations. The AI group had considerably elevated levels of total thiol and native thiol (SH) compared with the MA group. Nevertheless, there was no notable disparity observed between the group of healthy pregnancies and the other two groups. Serum disulfide (SS) levels did not exhibit any significant variations among the three groups. Similarly, the ratios of SS/SH, SS/total thiol, and SH/total thiol did not show any significant differences between the groups (p>0.05). Patients with MA had decreased levels of total thiol and SH, which possess antioxidant capabilities, compared to the AI group. A decrease in antioxidant levels in the body may contribute to the etiology of MA. When considering our findings alongside existing literature, it remains inconclusive whether the serum thiol-disulfide ratio can predict a healthy pregnancy or MA following AI. Therefore, it is not yet seen as a promising diagnostic tool for assessing pregnancy viability. Additional investigation is required to establish the influence of dynamic thiol/disulfide homeostasis on early pregnancy loss.

Multiple Myeloma from the Perspective of Pro- and Anti-Oxidative Parameters: Potential for Diagnostic and/or Follow-Up Purposes?

Multiple myeloma is a hematological malignancy characterized by anemia, antibodies causing kidney damage, and damage to multiple organs, which come together to cause morbidity. Although oxidative stress is not a core pathological aspect of multiple myeloma, reactive oxygen species (ROS) and antioxidant balance have been shown to play a role in the disease process and are considered in its management. In the presented study, we aim to assess the reliability of specific oxidant and antioxidant variables as potential biomarkers for multiple myeloma and to determine which of these variables might exhibit higher sensitivity in predicting multiple myeloma. This case-control study was conducted between March 2023 and August 2023. A total of 30 multiple myeloma patients, newly diagnosed according to the multiple myeloma diagnostic criteria revised by the International Myeloma Study Group in 2014, and a total of 30 volunteers without multiple myeloma were included in this study. Serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT), and malondialdehyde (MDA) and nitric oxide (NO) levels were measured with the first blood samples taken after inclusion. The groups had similar age (p = 0.623) and sex distribution (p = 1.000). MDA (cut-off: >4.35, p < 0.001), GSH-Px (<59.8, p < 0.001), CAT (<67.2, p < 0.001), SOD (<21.2, p = 0.001), and NO (>38.5, p < 0.001) could significantly detect multiple myeloma. Multivariate logistic regression revealed that increased MDA (p = 0.003) and NO (p = 0.001) levels and decreased GSH-Px (p = 0.001), CAT (p = 0.001), and SOD levels were independently associated with multiple myeloma disease. The presence of increased antioxidant levels and decreased antioxidant levels in patients with multiple myeloma is the clearest indicator of increased oxidative stress. These parameters may help to identify potential therapeutic targets and develop strategies to control disease progression.

Pulmonary toxicity associated with high-dose favipiravir and treatment options: biochemical and histopathological evaluation.

Favipiravir is a broad-spectrum antiviral drug that is a viral RNA-dependent RNA polymerase inhibitor. Favipiravir is used in high doses to treat COVID-19 but has a side effect on humans at high doses. The side effects of favipiravir have been associated with oxidative stress in the literature. In this trial, we investigated the biochemical and histopathological effects of lacidip-ine, thiamine pyrophosphate (TTP), and adenosine triphosphate (ATP), drugs with antioxidant properties, on the lung toxicity caused by high-dose favipiravir in rats. The rats were classified into five groups: healthy (HG), favipiravir alone (Fav), lacidipine+favipiravir (LFav), TPP+favipiravir (TFav), and ATP+favipiravir (AFav). Favipiravir (800 mg/kg) was administered twice daily for seven days. Laci-dipine (4 mg/kg), TPP (20 mg/kg), and ATP (25 mg/kg) were administered once daily for seven days. Oxidant (malondialdehyde), non-enzymatic (total glutathi-one), and enzymatic (superoxide dismutase and catalase) antioxidant levels were measured in the excised lung tissues. Furthermore, the tissues were histopatho-logically examined. The systemic administration of high doses of favipiravir in-creased oxidant levels and decreased antioxidant levels in the lung tissue of rats. In parallel, the histopathological examination of the lung tissue revealed the presence of severe mononuclear cell infiltrations in interstitial areas and pronounced lymphoid hyperplasia. Lacidipine exhibited superior efficacy in mit-igating oxidative stress and preventing the decline of antioxidants induced by favipiravir compared with TPP and ATP. Histopathologically, the lacidipine admin-istration significantly reduced lung oxidative damage. TTP moderately reduced severe favipiravir-associated lung injury. However, ATP was ineffective against fa-vipiravir-associated lung injury. Lacidipine offers more therapeutic benefits than TPP in treating oxidative lung injury caused by high doses of favipiravir.

Protective Effect of Ramipril Against Oxidant and Proinflammatory Cytokine Damage Induced by Ischemia-Reperfusion in Ovarian Tissue in Rats

It is known that the increase in oxidants and proinflammatory cytokines, as well as the decrease in antioxidants, play a role in ovarian ischemia-reperfusion (I/R) injury. The antioxidant and anti-inflammatory properties of ramipril have been studied in various diseases. This study aims to investigate the effect of ramipril on I/R-induced ovarian damage in rats. Rats were divided into healthy (HG), sham (SG), ovary I/R (OIR), and ramipril + ovary I/R (ROIR) groups (n = 6/each group). One hour before the surgical procedures, ROIR was given 2 mg/kg ramipril. The lower abdomen of the SG, OIR, and ROIR was surgically opened. Right ovarian tissues of OIR and ROIR were subjected to 2 hours of ischemia and 6 hours of reperfusion. Then, all animals were euthanized, and their right ovaries were removed. Ovarian tissues were examined for oxidants (malondialdehyde), antioxidants (total glutathione, superoxide dismutase, and catalase), and proinflammatory cytokines (nuclear factor kappa-B, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin-6) analysis was performed. Tissues were examined histopathologically. The ovarian tissue of the OIR, which underwent the I/R procedure, exhibited a significant increase in oxidant and proinflammatory cytokine levels, along with a decrease in antioxidant levels (P < .001). Ramipril suppressed the I/R-induced increase in oxidants and pro-inflammatory cytokines and the decrease in antioxidants (P < .001). Ramipril also attenuated I/R-induced histopathological damage in ovarian tissue (P < .05). Ramipril treatment may be a treatment strategy to protect ovarian tissue against oxidative and inflammatory damage of I/R.

α-Lipoic acid improves mitochondrial biogenesis and dynamics by enhancing antioxidant and inhibiting Wnt/Ca2+ pathway to relieve fluoride-induced hepatotoxic injury

Fluoride (F), widely present in water and food, poses a serious threat to liver health, and oxidative damage and mitochondrial damage are its main causes. As a natural mitochondrial protector and antioxidant, α-lipoic acid (ALA)'s alleviating effect on fluorosis liver injury and its underlying mechanism are still unclear. Therefore, this study established a fluorosis ALA intervention mice model to explore the mechanism of mitochondrial biogenesis, mitochondrial dynamics, and Wnt/Ca2+ pathway in ALA attenuating fluorosis liver injury. The results showed that ALA mitigated F-induced weight loss, hepatic structural and functional damage, hepatocytes mitochondrial damage, and decreased antioxidant levels. However, ALA did not reduce F accumulation in the femur. Further mRNA and protein detection results showed that F increased the expression levels of key genes in the mitochondrial fission (Drp1, Mff, and Fis1), mitophagy (Parkin, Pink1, and Prdx3), Wnt/Ca2+ pathway (Wnt5a and CaMK2), and rised the number and intensity of fluorescent spots of Drp1, but decreased the expression levels of key genes in the mitochondrial biogenesis (Sirt1, Sirt3, and PGC-1α) and fusion (OPA1, Mfn2, and Mfn1), and reduced the number and intensity of fluorescent spots of PGC-1α in the liver. However, the intervention of ALA relieved the F-induced changes in the expressions of the above genes. In conclusion, ALA mitigated F-induced hepatic injury through enhancing antioxidant capacity and inhibiting Wnt/Ca2+ pathway to improve mitochondrial biogenesis and dynamics disturbance. This study further reveals the hepatotoxic mechanism of F and the protective mechanism of ALA, and provides a theoretical basis for ALA as a potential preventive and palliative agent for F-induced hepatotoxic injury.

Insulin resistance and Oxidant-Antioxidant Markers in Young Women with Polycystic Ovarian Syndrome

Introduction: Oxidative stress and insulin resistance (IR) may contribute to the pathogenesis of polycystic ovarian syndrome (PCOS). IR promotes hyperglycaemia, which may increase the production of reactive oxygen species and decrease in antioxidant levels in PCOS. Aim: To investigate the oxidant-antioxidant status and its association with insulin resistance in young women with PCOS.Materials and methods: The present study involved two groups, PCOS (n = 55) and age and BMI matched controls (n = 55). Serum levels of various oxidative stress markers malondialdehyde (MDA), antioxidants- superoxide dismutase (SOD), catalase, and total antioxidant capacity (TAC) were measured using spectrophotometric assays. HOMA-IR method was used to assess the insulin resistance. Results were analysed to compare and correlate insulin resistance with these oxidative stress markers. Results: PCOS group had significantly higher MDA and lower TAC activity, SOD, catalase levels than the control group (p &lt; 0.001). PCOS patients with IR had significantly higher MDA, while SOD, catalase, TAC levels lower than the PCOS patients without IR (p&lt; 0.001). Infertile PCOS patients had significantly higher MDA, and lower SOD, catalase, TAC level than the fertile PCOS patients (p&lt;0.001). There was a statistically significant and positive correlation between HOMA-IR and MDA levels, whereas HOMA-IR showed statistically significant negative correlation with SOD, catalase and TAC levels. onclusion: Our findings suggest that young PCOS women may experience oxidative stress due to insulin resistance. As a result, the existence of insulin resistance, hyperinsulinemia, and oxidative damage in PCOS is likely to hasten the gradual progression of cardiovascular disease.

Elucidating the insecticidal mechanisms of zein nanoparticles on Anticarsia gemmatalis (Lepidoptera: Erebidae).

Previous research suggested that positively charged zein nanoparticles [(+)ZNP] were toxic to neonates of Anticarsia gemmatalis Hübner and deleterious to noctuid pests. However, specific modes of action for ZNP have not been elucidated. Diet overlay bioassays attempted to rule out the hypothesis that A. gemmatalis mortality was caused by surface charges from component surfactants. Overlay bioassays indicated that negatively charged zein nanoparticles [(-)ZNP] and its anionic surfactant, sodium dodecyl sulfate (SDS), exhibited no toxic effects when compared to the untreated check. Nonionic zein nanoparticles [(N)ZNP] appeared to increase mortality compared to the untreated check, though larval weights were unaffected. Overlay results for (+)ZNP and its cationic surfactant, didodecyldimethylammonium bromide (DDAB), were found to be consistent with former research indicating high mortalities, and thus, dosage response curves were conducted. Concentration response tests found the LC50 for DDAB on A. gemmatalis neonates was 208.82 a.i./ml. To rule out possible antifeedant capabilities, dual choice assays were conducted. Results indicated that neither DDAB nor (+)ZNP were antifeedants, while SDS reduced feeding when compared to other treatment solutions. Oxidative stress was tested as a possible mode of action, with antioxidant levels used as a proxy for reactive oxygen species (ROS) in A. gemmatalis neonates, which were fed diet treated with different concentrations of (+)ZNP and DDAB. Results indicated that both (+)ZNP and DDAB decreased antioxidant levels compared to the untreated check, suggesting that both (+)ZNP and DDAB may inhibit antioxidant levels. This paper adds to the literature on potential modes of action by biopolymeric nanoparticles.

Dexpanthenol ameliorates doxorubicin-induced lung injury by regulating endoplasmic reticulum stress and apoptosis.

Doxorubicin (DOX), which is used as a chemotherapeutic agent in the treatment of tumors, has limited use due to its toxicity in various organs and tissues. One of the organs where DOX has a toxic effect is the lung. DOX shows this effect by increasing oxidative stress, inflammation, and apoptosis. Dexpanthenol (DEX), a homologue of pantothenic acid, has anti-inflammatory, antioxidant, and anti-apoptotic properties. Therefore, the purpose of our investigation was to explore how DEX could counteract the harmful effects of DOX on the lungs. Thirty-two rats were used in the study, and 4 groups were formed (control, DOX, DOX + DEX, and DEX). In these groups, parameters of inflammation, ER stress, apoptosis, and oxidative stress were evaluated by immunohistochemistry, RT-qPCR, and spectrophotometric methods. In addition, lung tissue was evaluated histopathologically in the groups. While CHOP/GADD153, caspase-12, caspase-9, and Bax gene expressions increased in the DOX group, Bcl-2 gene expression levels significantly decreased. In addition, changes in Bax and Bcl-2 were supported immunohistochemically. There was a significant increase in oxidative stress parameters and a significant decrease in antioxidant levels. In addition, an increase in inflammatory marker (TNF-α and IL-10) levels was determined. There was a decrease in CHOP/GADD153, caspase-12, caspase-9, and Bax gene expressions and an increase in Bcl-2 gene expression in the DEX-treated group. In addition, it was determined that there was a decrease in oxidative stress levels and inflammatory findings. The curative effect of DEX was supported by histopathological findings. As a result, it was experimentally determined that DEX has a healing effect on oxidative stress, ER stress, inflammation, and apoptosis in lung damage caused by DOX toxicity.

Abstract 1840: Methylmalonic acid accumulation suppresses CD8+ T cell activation and contributes to age-induced immunosuppression

Abstract Deregulation of cytotoxic CD8+ T cells is a feature of the aging process with important consequences for anti-tumor immunity and consequently affects tumor initiation, progression, and response to immunotherapies. However, our understanding of how the aging process affects CD8+ T cells remains incomplete. Vitamin B12 deficiency is also a feature of old age caused by a well-recognized decrease in vitamin absorption. Interestingly, clinical studies have reported a significant decline in CD8+ T cells in individuals with vitamin B12 deficiency, suggesting that vitamin B12 levels might be a mechanistic link between aging and deregulation of CD8+ T cells. An important and often overlooked consequence of vitamin B12 deficiency is an elevation of methylmalonic acid (MMA) in circulation. Our laboratory has previously established a critical role for age-induced MMA in promoting progression into metastatic disease of breast and lung cancers, which coincided with a robust immunosuppressive signature. Here, we demonstrate that exposure of CD8+ T cells to MMA or culture of CD8+ T cells in the absence of vitamin B12 reduces T cell activation, thereby decreasing T cell numbers and effector function. Conversely, supplementation of vitamin B12 on CD8+ T cells isolated from old mice enhances their ability to activate and increases T cell numbers. Evaluation of the effects of MMA on the CD8+ T cells metabolome revealed a decrease in antioxidant levels, including a pronounced reduction in vitamin C and reduced glutathione, which were accompanied by an increase in both superoxide and hydrogen peroxide, suggesting that an increase in reactive oxygen species might be the link between MMA and CD8+ T cell dysfunction. Together, these results put forward the idea that MMA is an important regulator of immune cell function and that supplementation of vitamin B12 in older people and individuals diagnosed with vitamin B12 deficiency may function as an important strategy to improve immune cytotoxic responses and thereby increase anti-cancer immunosurveillance and the effectiveness of certain immunotherapies. Citation Format: Joanne D. Tejero, Stanislav Drapela, Juan Fernandez-Garcia, Sarah-Maria Fendt, Didem Ilter, Ana P. Gomes. Methylmalonic acid accumulation suppresses CD8+ T cell activation and contributes to age-induced immunosuppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1840.

Aerobic and resistance exercises affect the BDNF/TrkB signaling pathway, and hippocampal neuron density of high-fat diet-induced obese elderly rats.

Obesity, caused by a high-fat diet (HFD) in elderly, is a risk factor for insulin resistance and a precursor to diabetes and can lead to impaired cognitive function. Physical exercise has positive effects on decrease obesity and improvement brain function. We investigated which type of aerobic (AE) or resistance (RE) exercise can be more effective in reducing HFD-induced cognitive dysfunction in obese elderly rats. 48 male Wistar rats (19-monthold) were divided into six groups: Healthy control (CON), CON+AE, CON+RE, HFD, HFD+AE, and HFD+RE. Obesity was induced by 5 months of HFD feeding in older rats. After obesity confirmation, RT (with a range of 50% to 100%1RM/3 days/week) and AE (running at 8-m/min for 15-min to 26-m/min for 60-min /5 days/week) was performed for 12-weeks. Morris water maze Test was used to evaluate cognitive performance. All data were analyzed using two-way statistical test of variance. The results showed that obesity had a negative effect on glycemic index, increased inflammation, decreased antioxidant levels, decreased BDNF/TrkB and decreased nerve density in hippocampal tissue. The Morris water maze results clearly showed cognitive impairment in the obesity group. But 12 weeks after AE and RE, all the measured variables were on the improvement path, and in general, no difference was observed between the two exercise methods. Two mods of exercise (AE and RE) may be having same effects on nerve cell density, inflammatory, antioxidant and functional status of hippocampus of obese rats. Each of the AE and RE can create beneficial effects on the cognitive function of the elderly.

Kadmiyuma Maruz Bırakılan Farelerin Oksidatif Stres Parametreleri ve Kan Lipid Profili üzerinde Resveratrolun Dokuya Özgü İyileştirici Etkisi

Cadmium can cause oxidative damage in organisms through overproduction of free radicals and suppression of the antioxidant defense system. Resveratrol is known as a nutraceutical with antioxidant properties accepted to have protective effects to the toxicity of heavy metals. In this study, we investigated if resveratrol could overwhelm the toxic effect of sub-acute cadmium exposure. Animals were divided to the following groups: 1) Control, 2) Vehicle control, 3) Cadmium (Cd), 4) Resveratrol (Res), 5) Exposure to both Cd and Res (Cd+Res). Increased lipid peroxidation and total sialic acids were determined in testis and lung tissues of mice exposed to Cd with the decreased in paraoxonase (PON1) level and GSH amount. Interestingly, we also found an increased lipid peroxidation and NO levels in lung tissue of mice exposed to Res and Cd + Res, but not in testis tissue. Moreover, increased triglycerides, total cholesterol, very low-density lipoproteins, and low-density lipoproteins as well as reduced high-density lipoproteins were found in mice exposed to Cd and Cd + Res compared to controls. Our results revealed that cadmium induces oxidative damage in tissues, via increased lipid peroxidation, total sialic acids and decreased antioxidant levels as well as disturbs lipid profile. Moreover, our findings indicate that resveratrol may act as “ameliorative” factor against the cadmium exposure in only testis tissue. Thus, we may suggest that ameliorative effect of resveratrol may vary depending on the exposure dose, exposure duration and exposed tissues of animals to the heavy metals.

Does oxidative stress promote the effect of the paraoxonase enzyme family (PON) on cancer? A review study to clarify this relationship by PONs

Cancer development and progression are associated with oxidative stress. Oxidative stress can favor high concentrations of reactive oxygen species (ROS), and free radicals are associated with antioxidant metabolism. The human enzyme paraoxonase (PON) contributes to antioxidant metabolism and decreased antioxidant levels. This leads to a high-risk factor for coronary heart disease. This review focuses on specific changes that affect the DNA molecule, and signaling pathways, and regulate the various cancers through the attraction of PON, an enzyme for degrading lipid peroxides within the cell as well as lipoproteins in the bloodstream.