Antioxidant Defense System Research Articles

Genetic Adaptations of Soybean to Cold Stress Reveal Key Insights Through Transcriptomic Analysis.

Low temperatures greatly restrict the development, growth, and productivity of soybeans, with their effects differing across various cultivars. The present work investigated the transcriptome and physiological reactions of two soybean cultivars, namely "KD52" exhibiting cold tolerance and "DS17" displaying cold sensitivity, to cold stress across a precisely defined period. The soybean plants were subjected to cold treatment at 6 °C for durations of 0, 2, 4, and 8 h. A comparative physiological marker study revealed distinct reactions to cold stress in the two cultivars. The findings showed that increased malondialdehyde levels provided evidence of DS17's heightened vulnerability to lipid peroxidation and membrane degradation. In contrast, the KD52 cultivar exhibited increased activities of antioxidant enzymes, including peroxidase and superoxide dismutase, in response to cold exposure, suggesting a strong antioxidant defense system against oxidative stress. The transcriptomic analysis revealed dynamic responses, mapping 54,532 genes. Within this group, a total of 234 differentially expressed genes (DEGs) were found to be consistently changed at several time intervals, showing unique expression patterns across the two cultivars. Analysis of the association between these important DEGs and the physiological indicators revealed candidate genes that may be involved in controlling oxidative damage and antioxidant defenses. Some key genes showed a progressive rise in expression over time in both cultivars, with a more significant acceleration in KD52, and are probably involved in promoting adaptation processes during extended periods of cold exposure. The identification of improved defense mechanisms in KD52, together with the identification of crucial genes, offers great prospects for enhancing the cold stress resilience of soybean.

Effect of CCl4 on Renal Tissues of Male Mice and Prevented by Pretreatment with Bromelain Loaded with Gold Nanoparticles: Histopathological and Caspase-9 Expression Alterations

The study aimed to investigate the potential protective effect of bromelain on renal histopathological changes induced by carbon tetrachloride (CCl4) in albino mice. CCl4 is widely used in the chemical industry but is also known to cause toxicity to various organs including the brain, liver, kidneys and lungs. In this study, 49 animals were divided into 7 equal groups. The kidneys of the mice were examined to assess histopathological changes and immunohistochemical markers, specifically caspase-9. The groups that received bromelain solution coated with gold nanoparticles demonstrated greater protective effects against CCl4-induced kidney damage. The findings suggest that kidney damage induced by CCl4 may be attributed to oxidative stress, which disrupts the antioxidant defense system, enzyme function and biochemical markers. However, administration of bromelain significantly mitigated CCl4 toxicity by enhancing the antioxidant defense system and reducing the production of free radicals. Notably, the study found that a dose of 300 mg of bromelain effectively reduced CCl4-induced toxicity in rats. This highlights the potential therapeutic value of bromelain in protecting against chemical-induced kidney damage. HIGHLIGHTS The kidney damage from carbon tetrachloride can occur through oxidative stress, altering the antioxidant defense system, enzyme function, and biochemical markers. The bromelain can decreased the toxicity of CCL4. The 300 mg bromelain solution proved to be more efficacious than the 100 mg dose. GRAPHICAL ABSTRACT

UV-B radiation mitigates oxidative stress damage in postharvest Agaricus bisporus by modulating the antioxidant defense system

Agaricus bisporus (A. bisporus) has fragile tissues and is highly susceptible to post-harvest decay and spoilage, which affecting the development of the industry. Ultraviolet B (UV-B) irradiation, as a typical irradiation preservation technology, is effective in inducing the production of endogenous metabolic substances in organisms and enhancing their level of resistance. The objective of this study was to investigate the mechanism of activation of the antioxidant defence system in A. bisporus by UV-B irradiation, utilising a range of UV-B irradiation doses (0, 25, 50 and 100 kJ m−2). In this study we found that 50 kJ m−2 UV-B irradiation effectively delayed the accumulation of reactive oxygen species (ROS), inhibited NADPH oxidase (NOX) activity and the expression of Rbohf, PXMP2, PXMP4, APO, and MPV17. Moreover, it could increase the accumulation of ascorbate (AsA) and glutathione (GSH), enhance the activities of ascorbate peroxidase (APX) and glutathione peroxidase (GSH-PX), and it also effectively induce catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD) activities and up-regulate the expression levels of related genes. In addition, we found that UV-B irradiation upregulated the expression of UVR8 and suppressed the expression of PEX5, PEX11 and PMD1. These results suggest that 50 kJ m−2 UV-B irradiation could stimulate the UV Resistance Loucs 8 (UVR8) receptor, regulate peroxisome proliferation, and enhance the ability of A. bisporus to resist oxidative stress, thereby maintaining the cellular redox homeostasis, this provides a new strategy for the study of extended postharvest storage stability of A. bisporus.

Graphene oxide improves the tolerance of Tartary buckwheat to continuous cropping by coordinating the antioxidant defense system and endogenous hormone levels

Continuous cropping obstacles seriously restrict the yield of Tartary buckwheat. Graphene oxide (GO) is shown to play an important role in defense mechanism to plant abiotic stress. However, the relationship between GO and improving continuous cropping tolerance is unclear. The main objective of this study was to analyze the physiological mechanism of GO in alleviating continuous cropping injury. A 2-year field experiment was conducted on Tartary buckwheat (Jinqiao 2) to investigate the characteristics with five GO treatments, namely, 0 (control), 25 (G1), 50 (G2), 100 (G3), and 200 mg L–1 (G4). With increasing the GO application concentration, the rhizosphere soil nutrient content, root morphology and activity, photosynthetic characteristics and chlorophyll content, antioxidant enzyme activities, osmotica and auxin (IAA) content, agronomic traits, and yield initially increased and then decreased. The contents of malonaldehyde, superoxide anion free radical, and abscisic acid (ABA) initially decreased and then increased. Compared with CK, the yields subjected to continuous cropping and treated with G1, G2, G3, and G4 were 1.28, 1.58, 1.43, and 1.16 times, respectively. GO treatment, especially G2 treatment, can improve the tolerance and increase the yield of Tartary buckwheat to continuous cropping, and it is suitable for widespread use by farmers in Tartary buckwheat production.

Tissue oxidative stress and expression of chicken UCP and ANT mRNA in laying hens exposed to acute cold stress

ABSTRACT 1. Exposure to stress alters normal homoeostasis and, hence, the antioxidant defence system. The aim of this study was to examine the effect of acute cold temperature on the antioxidant defence system in hens. 2. Hy-line grey commercial layers (80 40-week-old) were randomly assigned to one of eight groups. In groups 1 to 5, hens were exposed to low temperature at −8.68°C (cool stressed) for 2, 4, 6, 8 and 10 h, respectively. In groups 6 and 7, post 10 h cool stressed, hens were quickly transferred to room at 21°C to recovery for 2 h and 4h, respectively. In treatment groups 6 and 7, post 10 h cool stressed, hens were quickly transferred to room at 21°C for 2 h and 4 h, respectively. Group 8 was the control, where hens were housed under regular condition at 21°C as controls. 3. Antioxidant enzymes (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA), in skeletal muscle, the kidney, liver and pancreas were measured. The transcription of avUCP and ANT mRNA was tested by RT-PCR. 4. The T-AOC activity was increased in the skeletal muscle of hens cold stressed for 2, 4, 6, 8 and 10 h and the 2 h recovery groups compared with control hens (p < 0.05). The GPx activity was increased in the liver and skeletal muscle after cold stress 4 h and in the pancreas of cold stress 2 h compared with the control group (p < 0.05). Antioxidant SOD activity was increased in the kidney after cold stress 6 h and in the liver after cold stress 10 h compared to the control group (p < 0.05). Measured MDA activity was increased in the pancreas after 2 h cold stress (p < 0.05). 5. UCP mRNA expression level was increased in the pectoral muscle for 2 h and 4 h recovery groups compared with the control hens (p < 0.05) and avian uncoupling protein (UPC), adenine nucleotide translocator (ANT) expression level was increased in the leg muscle of hens cold stress for 2, 6, 8 h and recovery 2 and 4 h. 6. The observed changes in the antioxidant defence system were tissue specific. Increments in levels of ANT (leg muscle) and UCP (pectoral and leg muscle) mRNA expression may be involved in the regulation of thermogenesis in skeletal muscle.

Choline supplementation reduces cadmium uptake and alleviates cadmium toxicity in Solanum lycopersicum seedlings

Sustainable plant production in soil polluted with heavy metals requires that novel strategies are developed for the benefit of humans and other living things. Cadmium (Cd) is a common heavy metal pollutant for plants, and there is limited information on the use of exogenous bio-regulators to reduce the accumulation and toxic effects of Cd pollution in plants. Choline is an endogenous quertarnary amine that is known to improve stress tolerance in plants, while its mechanism of action in certain conditions is yet to be determined. This study investigated the effects of foliar choline supplementation (10 mM) on Solanum lycopersicum seedlings exposed to Cd application (50 mg/L in soil). The seedlings were randomized to five groups: Control (E1), Cd stress (E2), Choline supplementation after Cd stress (E3), Choline (E4), and Choline supplementation before Cd stress (E5). Following the applications, the Cd content, growth and development parameters (chlorophyll content, fresh and dry weight), oxidative stress parameters (H2O2 and MDA contents), as well as antioxidative defense system (SOD, GSH, AsA, and TPC contents) were analyzed. Choline supplementation after Cd stress reduced the enhanced Cd content in roots by 38% but did not alter it in leaves (p > 0.05) compared to the Cd group. Choline supplementation before Cd stress decreased Cd content both in roots by 87.5% and in leaves by 50%. Choline supplementation after and before Cd stress increased fresh and dry weights in both roots and leaves. While the Cd group (E2) increased the H2O2 level and SOD activity, no remarkable change was observed in H2O2 levels in all choline supplementations (E3, E4, E5). Therefore, lipid peroxidation (MDA) was not observed in choline supplementation before Cd stress (E5), however, when the choline was applied after Cd stress (E3) MDA content was reduced by 40% compared with the Cd stress group (E2). Choline supplementations after and before Cd stress (E3, E5) increased AsA content by 30%, while the Cd group (E2) decreased it by 60% compared with the control group (E1). Choline supplementations before Cd stress (E5) increased TPC by 33%, while the Cd group (E2) decreased it by 18%, moreover, when choline was applied after Cd stress (E3), no change was observed compared to the control group. These data suggest that choline prevents inhibition of plant growth due to Cd toxicity by reducing Cd uptake. The results provided in the present study are likely to enhance the quality and efficiency of crop production in heavy metal-polluted areas.

The Potential of Nanotechnology in Anti-Cancer Drug to Regulate Nrf2 Signaling for Cancer Therapeutic Purposes.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a regulator of the cellular antioxidant defense system that plays an important role in reducing the risk of various pathophysiological conditions, including cancer. Targeting Nrf2 presents an attractive therapeutic approach to overcome these challenges and improve cancer treatment outcomes. Nanoparticles, with their unique physicochemical properties, offer several advantages over conventional therapies for targeting Nrf2. These include enhanced stability, improved permeability and retention effect, and precise targeting capabilities. Moreover, delivery systems based on nanotechnology have shown promise in overcoming the limitations of conventional cancer therapies, including ineffective precision targeting and momentous complications. The therapeutic efficacy of Nrf2 inhibitors may be enhanced by using nanoparticles for specific drug targeting and deeper tissue penetration. This involves optimizing nanoparticle formulations, understanding their interactions with the biological environment, and ensuring their safety and biocompatibility. Effective nanoparticle formulations are being developed to transport Nrf2 inhibitors, which can significantly improve treatment outcomes and address the limitations of conventional cancer therapies. Further studies are needed to explore the potential of nanotechnology in targeting Nrf2 for cancer therapeutic purposes.

Glycosylation of chrysin with β-d-glucose tetraacetate (LQFM280) enhances its in vitro and in vivo neuroprotective effects against the toxicity induced by 3-nitropropionic acid.

Chrysin (CHR) is a naturally occurring flavonoid found in the human diet, recognized for its potential in preventing neurodegenerative diseases. However, its limited water solubility restricts its bioavailability and therapeutic applications. To address this issue and bolster the neuroprotective properties of CHR for potential nutraceutical or medicinal use, we investigated a novel compound, LQFM280, formed by conjugating CHR with β-d-glucose tetraacetate. We conducted both in vitro (using SH-SY5Y cells, mutant STHdhQ111/Q111 cells, and wild-type STHdhQ7/Q7 cells), and in vivo (mice) neurotoxicity experimental model induced by 3-nitropropionic acid, which mimic biological changes akin to Huntington's disease in humans. Compared to non-glycosylated CHR, LQFM280 showed superior in vitro effects in preventing neurotoxicity caused by increased mitochondrial vulnerability due to mutant huntingtin. In vivo findings demonstrated that LQFM280 has heightened efficacy in mitigating weight loss, memory and locomotor impairment, oxidative stress, and disruptions in the antioxidant defense system, as well as succinate dehydrogenase, and cholinesterase activities induced by 3-nitropropionic acid. These findings underscore the significant enhancement of chrysin's neuroprotective effects through glycosylation with β-d-glucose tetraacetate, positioning it as a promising candidate for use as a nutraceutical or food supplement to promote health benefits.

Effect of CAT gene polymorphism on sensitivity of human lymphocytes to genotoxic effect of organochlorine pesticide in vitro

Introduction. Over recent decades, toxicogenetic studies have focused on the issues of genome instability under the action of genotoxicants, taking into account biomarkers of sensitivity. The question about the genotoxic potential of chlorpyrifos remains open, since both positive and negative effects have been revealed in various tests. The aim of the study is the investigation of sensitivity of donor peripheral blood lymphocytes to chlorpyrifos in vitro and evaluation of the contribution of polymorphism of antioxidant defense system genes (CAT (rs1001179), SOD2 (rs4880)) to the response of human cells to the action of genotoxicant. Materials and methods. The DNA damaging effect of chlorpyrifos was assessed on lymphocytes from fifty two donors using DNA-comet assay with metabolic activation (+S9) and without it (–S9). The study of cytotoxic effects of chlorpyrifos on human lymphocytes was carried out using an automatic fluorescent cell analyzer ADAMII LS. Results. Chlorpyrifos had a pronounced cytotoxic effect on lymphocytes in most donors in the absence of metabolic activation system. With increasing concentration of the pesticide in the medium and time of cultivation, the viability of lymphocytes decreased, and the proportion of cells in late apoptosis and necrosis increased. Positive genotoxic effects were found on the cells of 33 donors (-S9). In the presence of the S9, mild but statistically significant effects were detected only on cells from 2 donors. % DNA values in the comet tail after exposure to the pesticide varied for cells from different donors. In the absence of metabolic activation, a statistically significant increase in the level of DNA damage was found in cells of individuals with genotype AA (homozygote for the minor allele) for the CAT G262A catalase gene (rs1001179), compared with homozygote for the dominant GG allele. Limitations. The genotoxicity of chlorpyryfos was studied in vitro. Conclusion. The results of the study shown cytotoxic and genotoxic effects of chlorpyrifos. The sensitivity of lymphocytes from different donors to the pesticide was found to be significantly different. The association of the level of DNA damage under exposure of chlorpyrifos in vitro with the G262A polymorphism of the catalase gene was found. The research also confirms the possibility of using a model test-system with peripheral blood lymphocytes to assess the potential genetic risk for humans and to study the contribution of gene polymorphism to individual sensitivity to the action of genotoxicants.

Neurobehavioral and bioaccumulative toxicity in adult in-vivo zebrafish model due to prolonged cadmium exposure in the presence of ketoprofen.

Increasing industrial activity causes the release of chemical compounds into aquatic habitats, including toxic heavy metals like cadmium and medications like ketoprofen, posing considerable ecological concerns. Although previous studies have shown that cadmium and ketoprofen individually cause cognitive impairment, there is a lack of information on the combined neurological effects of the two substances. We investigated the neurological consequences of persistent cadmium exposure in the presence of ketoprofen on adult zebrafish, providing an essential model for understanding cumulative impacts on vertebrate organisms. Behavioral assessments, bioaccumulation rates, biochemical studies, and histopathological exams were conducted over 42 days in authentic environmental settings. The results of our study show that cadmium (10 µg/L) and ketoprofen (10 and 100 µg/L) at environmentally relevant concentrations had a significant impact on locomotor activity, social interactions, and cognitive responses, indicating cumulative neurotoxicity in co-exposure groups compared to single pollutant groups. Biochemical tests show disturbances in antioxidant defense systems, while histological examinations reveal structural changes in zebrafish brain regions. Ketoprofen influences cadmium accumulation in the brain, underscoring the importance of conducting complete evaluations to understand the intricate interactions between environmental pollutants. This study improves our understanding of the complex interactions between heavy metals and medications, stressing the need to consider combined exposure when assessing the neurological effects on vertebrate models.

The effect of major depressive disorder comorbidity on ischemia-modified albumin levels, a marker of oxidative stress, and antioxidant defense system in patients with obsessive compulsive disorder.

The aim of this study was to examine the levels of oxidant and antioxidant markers in patients with obsessive-compulsive disorder (OCD) and to investigate whether these levels change in the presence of major depressive disorder (MDD) comorbidity. This study was completed with 23 OCD patients with MDD comorbidity (OCD+MDD), 21 OCD patients without MDD comorbidity (OCD-MDD) and 21 healthy controls. Oxidative stress levels of the cases' were determined by ischemia modified albumin (IMA) and malondialdehyde (MDA) measurements and antioxidant levels were determined by superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) measurements. One-way analysis of variance (ANOVA) and unpaired Student's t-test were used to compare the study groups. Post hoc Bonferroni test was used for the degree of significance between groups, and repeated measures analysis of covariance (ANCOVA) was used to investigate the effect of age and gender. IMA and MDA levels were significantly higher in the OCD group compared to the control group, and SOD, CAT and GSH-Px levels were lower in the OCD group compared to the control group (p<0.01). IMA levels were significantly higher in the OCD+MDD group compared to the OCD-MDD group, while SOD, CAT and GSH-Px levels were significantly lower in the OCD+MDD group compared to the OCD-MDD group (p<0101). MDA levels were significantly higher in the OCD+MDD group compared to the OCD-MDD group (p=0.009). When the entire OCD patient group was examined, significant, powerful, positive correlations were observed between Y-BOCS and HDRS scores and IMA and MDA, and significant powerful negative correlations between Y-BOCS and HDRS scores and SOD, CAT, and GSH-Px (p<0.001 for all). In OCD+MDD group, oxidative stress markers increased significantly in parallel with the severity of depression, while antioxidant levels decreased (p=0.003 for IMA, p<0.001 for others). We believe that parameters indicating impaired oxidant/antioxidant balance in patients with obsessive-compulsive disorder may help to elucidate the cause of the disease and may be potentially useful biomarkers in the diagnosis and determination of the severity of comorbid MDD.

Synergistic application of melatonin and silicon oxide nanoparticles modulates reactive oxygen species generation and the antioxidant defense system: a strategy for cadmium tolerance in rice.

Unfavorable environmental conditions pose a major barrier to sustainable agriculture. Among the various innovative strategies developed to protect plants from abiotic stress, the use of phytohormones and nanoparticles as "stress mitigators" has emerged as one of the most important and promising approaches. The objective of this study was to observe the protective role of melatonin (Mel) and silicon oxide nanoparticles (SiO-NPs) in rice (Oryza sativa L.) seedlings under cadmium (Cd) stress. Rice seedlings have reduced growth and phytochemical attributes when grown in Cd-contaminated (0.8 mM) pots. Seedlings under Cd stress had 38% less shoot length (SL), 53% total soluble sugar (TSS) and 57% protein content. However, superoxide dismutase (SOD), hydrogen peroxide (H2O2) and malondialdehyde (MDA) increased by 51%, 37% and 34%, respectively, under Cd stress. Beside this, activities such as peroxidase (POX) also elevated in the plants subjected with Cd-stress. In contrast, Mel (100 µm) as foliar spray and SiO-NPs (100 mg/L) as root dipping reduced oxidative stress in rice seedlings under Cd stress by reducing reactive oxygen species (ROS) generation. Furthermore, the application of Mel and/or SiO-NPs significantly increased the activity of antioxidative enzymes that scavenge ROS. The combined application of SiO-NPs and Mel increased growth, gas exchange and photosynthetic attributes, chlorophyll value, and protein content. It causes alleviation in the activity of SOD, CAT and POX by 73%, 62% and 65%, respectively. Overall, this study findings show that Mel and/or SiO-NPs can potentially protect the rice crop against oxidative damage under Cd stress.

Foliar application of esculin and digitoxin improve the yield quality of salt-stressed flax by improving the antioxidant defense system

BackgroundSecondary metabolites of several plants, including esculin and digitoxin, which are cardiac glycosides, were previously employed for their therapeutic effects. The current study aims to investigate the functions of the main Na+ /K+ transport inhibitor digitoxin and the antioxidant esculin for enhancing flax plant growth and production under salinity.MethodologyFlax plants were irrigated with distilled water supplemented with 0.0 and 5000 mg/L salt solution starting from 15 DAS from sowing. Then exogenous treatment with digitoxin and esculin with 50 mg L− 1 and 100 mg L− 1 were used for this work.ResultsAccording to the results of this work, foliar spraying of esculin or digitoxin increased the salinity tolerance of flax plants.The foliar application of either esculin or digitoxin induced an elevation in the contents of photosynthetic pigments, osmolytes including soluble sugar and proline as well as the total phenols in salt-stressed flax plants. Moreover, esculin and digitoxin in particular counteract oxidative stress by increasing the activity of antioxidant enzymes including superoxide dismutase, catalase, peroxidase, phenylalanine ammonia-lyase, and tyrosine ammonia lyase, leading to a decrease in reactive oxygen species and lipid peroxidation levels and electrolyte leakage. The efficiency of esculin and digitoxin to sustain ion homeostasis by inhibiting Na+ absorption and increasing potassium, calcium, and phosphorus in flax plants may be the reason for their protective actions towards salinity.As a consequence, esculin and digitoxin increased yield quantity and quality as shown by increases in all investigated yield criteriaas shoot height, root length, their fresh and dry weights as well asseed yield/plant (g), and 1000 seeds weight, especially those that improved the desired oil properties.ConclusionIn conclusion, this study concluded that digitoxin was more effective in inhibiting Na+ build-up and increasing flax salinity tolerance, particularly at the high investigated dose as compared to esculin. In this study, we reported the recent findings of exogenousapplication of either digitoxin or esculin glycosides which are new investigated salt alleviators never used before for improving the salt tolerance in flax plants.

Proline metabolism is essential for alkaline adaptation of Nile tilapia (Oreochromis niloticus)

BackgroundSaline-alkaline water aquaculture has become a key way to mitigate the reduction of freshwater aquaculture space and meet the increasing global demand for aquatic products. To enhance the comprehensive utilization capability of saline-alkaline water, it is necessary to understand the regulatory mechanisms of aquatic animals coping with saline-alkaline water. In this study, our objective was to elucidate the function of proline metabolism in the alkaline adaptation of Nile tilapia (Oreochromis niloticus).ResultsExpose Nile tilapia to alkaline water of different alkalinity for 2 weeks to observe changes in its growth performance and proline metabolism. Meanwhile, to further clarify the role of proline metabolism, RNA interference experiments were conducted to disrupt the normal operation of proline metabolic axis by knocking down pycr (pyrroline-5-carboxylate reductases), the final rate-limiting enzyme in proline synthesis. The results showed that both the synthesis and degradation of proline were enhanced under carbonate alkalinity stress, and the environmental alkalinity impaired the growth performance of tilapia, and the higher the alkalinity, the greater the impairment. Moreover, environmental alkalinity caused oxidative stress in tilapia, enhanced ion transport, ammonia metabolism, and altered the intensity and form of energy metabolism in tilapia. When the expression level of the pycr gene decreased, the proline metabolism could not operate normally, and the ion transport, antioxidant defense system, and energy metabolism were severely damaged, ultimately leading to liver damage and a decreased survival rate of tilapia under alkalinity stress.ConclusionsThe results indicated that proline metabolism plays an important role in the alkaline adaptation of Nile tilapia and is a key regulatory process in various biochemical and physiological processes.

Emerging insights into ferroptosis in cholangiocarcinoma (Review).

Cholangiocarcinoma (CCA) is a malignant tumor that arises within the biliary system, which exhibits a progressively increasing incidence and a poor patient prognosis. A thorough understanding of the molecular pathogenesis that drives the progression of CCA is essential for the development of effective molecular target therapeutic approaches. Ferroptosis is driven by excessive iron accumulation and catalysis, lipid peroxidation and the failure of antioxidant defense systems. Key molecular targets of iron metabolism, lipid metabolism and antioxidant defense systems involve molecules such as transferrin receptor, ACSL4 and GPX4, respectively. Inhibitors of ferroptosis include ferrostatin-1, liproxstatin-1, vitamin E and coenzyme Q10. By contrast, compounds such as erastin, RSL3 and FIN56 have been identified as inducers of ferroptosis. Ferroptosis serves a notable role in the onset and progression of CCA. CCA cells exhibit high sensitivity to ferroptosis and aberrant iron metabolism in these cells increases oxidative stress and iron accumulation. The induction of ferroptosis markedly reduces the ability of CCA cells to proliferate and migrate. Certain ferroptosis agonists, such as RSL3 and erastin, cause lipid peroxide build up and GPX4 inhibition to induce ferroptosis in CCA cells. Current serological markers, such as CA-199, have low specificity and cause difficulties in the diagnosis of CCA. However, novel techniques, such as non-invasive liquid biopsy and assays for oxidative stress markers and double-cortin-like kinase 1, could improve diagnostic accuracy. CCA is primarily treated with surgery and chemotherapy. A close association between the progression of CCA with ferroptosis mechanisms and related regulatory pathways has been demonstrated. Therefore, it could be suggested that multi-targeted therapeutic approaches, such as ferroptosis inducers, iron chelating agents and novel modulators such as YL-939, may improve treatment efficacy. Iron death-related genes, such as GPX4, that are highly expressed in CCA and are associated with a poor prognosis for patients may represent potential prognostic markers for CCA. The present review focused on molecular targets such as p53 and ACSL4, the process of targeted medications in combination with PDT in CCA and the pathways of lipid peroxidation, the Xc-system and GSH-GPX4 in ferroptosis. The present review thus offered novel perspectives to improve the current understanding of CCA.

Effect of a Commercial Polyphenol Compound on the Performance and Antioxidant Status of Penaeus vannamei

The study evaluated the effect of a commercial polyphenol (ELIFE®) on the growth performance and antioxidant defense system of Penaeus vannamei juveniles. The study was completely randomized with three experimental groups and eight repetitions, divided into two 28-day phases. The experimental groups consisted of different dietary inclusion levels of ELIFE® (0.0, 0.5, and 1.0 g kg−1). Five shrimps were stocked in each experimental unit. Growth performance, oxidative stress, and enzymatic activity in shrimp hepatopancreas were assessed. In Phase 1, shrimp fed ELIFE®, regardless of inclusion level, displayed higher specific growth rate, final weight, and final length than the control group. In Phase 2, shrimp fed 1.0 g kg−1 ELIFE® showed higher final biomass and SGR than all other experimental groups; they also displayed increased reduced glutathione and glutathione-S-transferase activities. In both test phases, shrimp fed 1.0 g kg−1 ELIFE® presented increased glutathione reductase activity compared to all other experimental groups. In both test phases, shrimp fed ELIFE®, regardless of inclusion level, exhibited increased glutathione peroxidase activity compared to control groups. Thus, ELIFE® enhanced the antioxidant defense system of P. vannamei and led to better shrimp performance and survival. This study recommends dietary supplementation with 1.0 g kg−1 ELIFE® for P. vannamei juveniles.

Level of prooxidant-antioxidant status in highly productive cows with comorbid obstetric, gynecological and orthopedic pathology

The lipid peroxidation and antioxidant defense system is a balanced system responsible for the processing and utilization of lipids in the body’s cells. It plays an important role in lipid metabolism, cell protection and overall health of the body. Its proper functioning is necessary to ensure optimal functioning of cells and organs throughout the body. The article clinically and experimentally substantiates the pathogenetic role of lipid peroxidation products and the level of antioxidant protection in cows with endometritis and purulent-necrotic processes in the finger area, as well as with the comorbid course of endometritis and orthopedic pathology. It has been shown that multimorbid manifestation is accompanied by a more severe course than individual diseases. It has been established that the development of postpartum endometritis and purulent-necrotic lesions of the limbs in cows is accompanied by a highly significant increase in lipid peroxidation products in the blood serum against the background of a decrease in the amount of antioxidant enzymes, with the exception of ceruloplasmin. Moreover, these changes are accompanied by a sharp jump in the comorbid course of endometritis and orthopedic pathology in highly productive animals.

Protective effect of reduced glutathione on acute kidney injury in lung cancer patients treated with cisplatin: a retrospective cohort study

Background Cisplatin is a common cause of acute kidney injury (AKI) during chemotherapy for lung cancer, and the nephrotoxicity limits its clinical use. Reduced glutathione (GSH) is a major component of the cellular antioxidant defense system and performs important physiological functions. The aim of this study was to analyze the protective effect of GSH on AKI in lung cancer patients treated with cisplatin. Methods The clinical data were retrospectively collected from lung cancer patients treated with cisplatin at our hospital between 1 January and 31 December 2019. The patients were divided into AKI group and non-AKI group based on whether AKI occurred, and into GSH group and non-GSH group based on whether GSH was used. Univariate and multivariate logistic regressions were used to analyze the risk factors for AKI. Results A total of 1372 lung cancer patients treated with cisplatin were enrolled. Of these patients, 231 patients (16.8%) developed AKI. The incidence of AKI was lower in the GSH group compared with the non-GSH group (10.6% vs. 18%, p = 0.009). Multivariate logistic regression analysis indicated that older age (OR = 1.045, 95% CI 1.025–1.065, p < 0.001), anemia (OR = 2.436, 95% CI 1.800–3.298, p < 0.001), higher SUA levels (OR = 1.002, 95% CI 1.000–1.004, p = 0.012), higher total amount of cisplatin per cycle (OR = 1.015, 95% CI 1.004–1.025, p = 0.005), and combination with paclitaxel (OR = 2.099, 95% CI 1.435–3.070, p < 0.001) were independent risk factors for AKI in lung cancer patients treated with cisplatin, whereas GSH (OR = 0.573, 95% CI 0.353–0.931, p = 0.025) and mannitol (OR = 0.229, 95% CI 0.055–0.963, p = 0.044) reduced the risk of AKI. Conclusion GSH was an independent protective factor against AKI in lung cancer patients treated with cisplatin and could be considered for clinical use in these patients to better protect renal function.

Development of novel dual-target drugs against visceral leishmaniasis and combinational study with miltefosine

The dual-target inhibitors (ZINC000008876351 and ZINC000253403245) were identified by utilizing an advanced computational drug discovery method by targeting two critical enzymes such as FeSODA (Iron superoxide dismutase) and TryR (Trypanothione reductase) within the antioxidant defense system of Leishmania donovani (Ld). In vitro enzyme inhibition kinetics reveals that both the compound's ability to inhibit the function of enzyme LdFeSODA and LdTryR with inhibition constant (Ki) value in the low μM range. Flow cytometry analysis, specifically at IC50 and 2X IC50 doses of both the compounds, the intracellular ROS was significantly increased as compared to the untreated control. The compounds ZINC000253403245 and ZINC000008876351 exhibited strong anti-leishmanial activity in a dose-dependent manner against both the promastigote and amastigote stages of the parasite. The data indicate that these molecules hold promise as potential anti-leishmanial agents for developing new treatments against visceral leishmaniasis, specifically targeting the LdFeSODA and LdTryR enzymes. Additionally, the in vitro MTT assay shows that combining these compounds with miltefosine produces a synergistic effect compared to miltefosine alone. This suggests that the compounds can boost miltefosine's effectiveness by synergistically inhibiting the growth of L. donovani promastigotes. Given the emergence of miltefosine resistance in some Leishmania strains, these findings are particularly significant.

Взаємозв’язок активності ферментативної та неферментативної ланок антиоксидантної системи організму залежно від тонусу автономної регуляції

The purpose of the study is to establish the nature of the influence of autonomic nervous regulation on the activity of the antioxidant defense system of broiler chickens. For the study of autonomic nervous regulation, Cobb 500 chickens crossbred were used. Autonomic nervous regulation was studied by variation pulsometry in chickens 30-35 days old, after which reference representatives of three types of tone of autonomic regulation were selected: sympathicotonic, normotonic and vagotonic. It was established that the average value of superoxide dismutase activity in sympathicotonic chickens is statistically higher than in normotonic chickens, which indicates a more active oxygen consumption in sympathicotonic chickens. As a result, the formation of superoxide radical increases, which requires more superoxide dismutase to accelerate its neutralization. In 60-day-old sympathicotonic chickens, indicators of superoxide dismutase activity remain at a lower level than in normotonic chickens, and in vagotonic chickens, a downward trend is noted. The indicator of glutathione peroxidase with the predominance of the sympathetic department of autonomic regulation is statistically lower than vago- and normotonic. A correlation was determined between superoxide dismutase and retinol level in 35-day-old normotonic chickens, which indicates the mutual coordination of the work of the enzymatic and non-enzymatic link of the antioxidant system under the condition of balanced autonomous regulation. However, with age, the parasympathetic division of the autonomic nervous system increases the influence on the relationship between superoxide dismutase and retinol in vagotonic chickens, in contrast to normotonic ones. It was found that the level of relationships between catalase and tocopherol increases with age in chickens with a vagotonic type of autonomous regulation. It has been proven that the level of tocopherol and retinol in 35-day-old vagotonic chickens is higher than that of normotonic chickens. Hens of the sympathicotonic and normotonic groups had a lower level of tocopherol in the blood plasma than in vagotonic hens. The level of retinol in the blood plasma of chickens with vagotonic type of autonomous nervous regulation is higher than that of normotonic and sympathicotonic chickens. This indicates the highest level of antioxidant protection in vagotonic chickens, which forms a solid foundation for higher immune status and growth in such birds.