Search Results (187)

Manganese (Mn) toxicity, commonly triggered by soil acidification, poses a significant threat to citrus production. Arbuscular mycorrhizal (AM) fungi can alleviate heavy metal stress, while their specific function and quantitative effectiveness in conferring Mn tolerance to citrus remain unclear. This study investigated the physiological regulation conferred by four AM fungal species, Rhizophagus intraradices (Ri), Funneliformis mosseae (Fm), Paraglomus occultum (Po), and Diversispora epigaea (De), on trifoliate orange (Poncirus trifoliata L. Raf.) under Mn stress. Mn toxicity reduced root colonization in a species-dependent manner, significantly lowering colonization by all AM fungal isolates except Fm. It also severely inhibited plant growth and induced pronounced oxidative damage, accompanied by metabolic imbalance. Under Mn-stressed conditions, AM fungal inoculation, especially Ri, significantly enhanced plant biomass relative to the non-AM control, with respective increases of 148% in leaves, 33% in stems, and 64% in roots, demonstrating a marked species-specific efficacy. Furthermore, AM symbiosis effectively promoted chlorophyll index and limited Mn translocation to the leaves under both non-stress and Mn-stress conditions, with Ri being the most effective in reducing leaf Mn content. Symbiosis with AM fungi, particularly Ri, fine-tuned the antioxidant enzyme defense under Mn stress by selectively suppressing superoxide dismutase and peroxidase activities while further boosting catalase activity. Concurrently, AM fungi alleviated Mn-induced oxidative damage, with the magnitude of mitigation varying by species: Ri delivered the most comprehensive protection, most effectively reducing hydrogen peroxide and malondialdehyde levels in both leaves and roots, whereas Po was particularly effective in suppressing root superoxide anion radical and malondialdehyde levels in roots. Furthermore, AM fungi reversed Mn-induced shifts in organic osmolytes: they significantly reduced the excessive accumulation of soluble sugars and proline while mitigating the loss of soluble proteins, thereby assisting in restoring metabolic homeostasis. The alleviative effects varied significantly among AM fungal species, with Ri identified as the most efficient and Mn-tolerant strain. These findings highlight the potential of utilizing specific AM fungi, particularly Ri, as a sustainable biological strategy to enhance citrus productivity in acidified, Mn-contaminated soils. Full article

Manganese (Mn) is a crucial micronutrient for plants. The impaired function of the oxygen-evolving complex in Photosystem II (PSII) due to Mn deficiency is believed to result in the overproduction of reactive oxygen species and the induction of an enzymatic antioxidant system. In our study, we investigated the effects of progressive Mn deficiency (the difference in Mn content between the needles of control and Mn-deficient plants increased from 17-fold at the beginning of the experiment to 59-fold at the end) on the activities of superoxide dismutase (SOD), catalase, ascorbate peroxidase, and guaiacol peroxidase in the roots and needles of Scots pine seedlings. We found that the soluble protein content in plant organs under Mn deficiency was maintained at a level comparable to that of the control. Regardless of the severity of Mn deficiency, the needles of the Mn-deficient plants presented twofold lower SOD activity than the needles of the control plants. These differences were observed even when Mn deficiency did not negatively affect plant growth. Additionally, the total SOD activity in the needles of both plant groups was determined solely by the activity of the Cu/Zn-containing SOD isozymes. Compared with the control plants, Mn deficiency did not result in an increase in any of the studied H₂O₂-degrading enzymes in the needles of the seedlings. In contrast, the needles of the Mn-deficient plants presented a lower level of guaiacol peroxidase activity. Despite the inhibition of root growth, Mn deficiency led to changes in the balance of the enzymatic antioxidant system in plant roots. The data obtained suggest that the lack of activation of SOD and other antioxidant enzymes in Scots pine seedlings against the background of progressive Mn deficiency is due to the reduced ability of PSII to generate ROS under these conditions. Full article

Background: Oxidative stress arises from an imbalance between excessive oxidant production and impaired antioxidant defense systems. This imbalance leads to biomolecular damage, contributing to aging and age-related diseases such as chronic kidney disease (CKD). Oxidative stress is a well-established risk factor for CKD and has been reported to accelerate disease progression. Hesperidin, a flavanone glycoside abundant in citrus fruits, exhibits antioxidant, anti-hypertensive, and anti-inflammatory properties and has been suggested to attenuate CKD progression. However, its potential role in reversing oxidative damage in kidney cells remains unclear. Methods: This study aimed to investigate whether hesperidin can reverse oxidative damage in human kidney proximal tubular epithelial (HK-2) cells. Oxidative stress was induced by exposing HK-2 cells to 500 μM hydrogen peroxide (H₂O₂) for 6 h, followed by treatment with 100 μM hesperidin for 24 h. Results: Our results showed that hesperidin significantly ameliorated H₂O₂-induced cytotoxicity. In the hesperidin post-treatment group (H₂O₂ + hesperidin), the expression of the antioxidant gene manganese superoxide dismutase (MnSOD) and the longevity-associated gene sirtuin 1 (SIRT1) was upregulated, while the expression of the senescence-associated gene β-galactosidase was downregulated compared to the H₂O₂-only treatment. Conclusions: These findings suggest that hesperidin promotes recovery from oxidative injury in kidney cells by enhancing antioxidant and longevity pathways and reducing cellular senescence. This may contribute to improved renal health and potentially slow CKD progression in patients suffering from oxidative stress-related kidney damage. Full article

Atypical antipsychotics (AAP), including clozapine (Clo), aripiprazole (Ari), and risperidone (Ris), are widely used in psychiatry but can lead to kidney damage due to oxidative stress. This study investigated whether dietary supplementation with selected antioxidants—ellagic acid, vitamin C, zinc, and seleno-methionine (SeMet) in fish oil, formulated as the composite product “ProCloSupp” (PCS)—can mitigate the oxidative damage induced by subchronic administration of AAP. Rats were treated with each antipsychotic for 28 days, with PCS added in the last 14 days. The kidney tissue was examined histologically and by determining the activities of antioxidant enzymes (copper, zinc and manganese superoxide dismutase—CuZn SOD and Mn SOD, catalase—CAT, glutathione peroxidase—GPx, glutathione reductase—GR, glutathione S-transferase—GST). All AAPs caused discrete to moderate renal damage and significant changes in enzyme profiles, which were most pronounced with Ari. Clo and Ari significantly decreased CuZn SOD and Mn SOD activity, while Ris only affected Mn SOD. Clo additionally increased CAT activity, while Ari increased GPx activity. Antioxidant-related protein levels increased only in the Ris group. PCS supplementation increased CuZn SOD and GPx activities and was associated with less pronounced histopathological changes than antipsychotic treatment alone. In conclusion, subchronic Clo, Ari, and Ris exposure induces oxidative renal damage in rats, while PCS supplementation enhances antioxidant defences and attenuates tissue damage. These results support PCS as a potential nephroprotective strategy in antipsychotic therapy. Full article

This study aimed to elucidate the physiological, biochemical, and transcriptional regulatory responses of potato plants to iron deficiency stress. Two potato varieties were selected for analysis: 05P (high tuber iron content) and CI5 (low tuber iron content). Tissue culture seedlings of both varieties were subjected to iron deficiency, and the effects on stem length, root length, fresh weight, soluble sugar and protein contents, as well as the activities of superoxide dismutase (SOD), peroxidase (POD), malondialdehyde (MDA), and leaf chlorophyll content (SPAD) values were evaluated. Additionally, the impact of iron deficiency on zinc (Zn), magnesium (Mg), calcium (Ca), manganese (Mn), and copper (Cu) concentrations in different tissues were analyzed. Transcriptomic sequencing and quantitative real-time PCR (qRT-PCR) were performed on various seedling tissues. The results showed that iron deficiency significantly inhibited seedling growth and development, resulting in reduced plant height and fresh weight, increased root length, decreased leaf SPAD content, and elevated soluble sugar and protein concentration. SOD, POD, and MDA activities were also significantly increased. Elemental analysis revealed that iron deficiency enhanced the uptake and accumulation of Zn, Mg, Ca, Mn, and Cu across different tissues. Transcriptomic analysis identified differentially expressed genes (DEGs) significantly enriched in pathways related to photosynthesis, carbon metabolism, and ribosome function in roots, stems, and leaves. Iron deficiency induced the upregulation of H⁺-ATPase genes in roots (PGSC0003DMG400004101, PGSC0003DMG400033034), acidifying the rhizosphere to increase active iron availability. Subsequently, this was followed by the upregulation of FRO genes (PGSC0003DMG400000184, PGSC0003DMG400010125, PGSC0003DMG401009494, PGSC0003DMG401018223), which reduce Fe³⁺ to Fe²⁺, and activation of IRT genes, facilitating Fe²⁺ transport to various tissues. Iron deficiency also reduced SPAD content in leaves, negatively impacting photosynthesis and overall plant growth. In response, the osmotic regulation and antioxidant defense systems were activated, enabling the plant to mitigate iron deficiency stress. Additionally, the absorption and accumulation of other metal ions were enhanced, likely as a compensatory mechanism for iron scarcity. At the transcriptional level, iron deficiency induced the expression of genes involved in metal absorption and transport, as well as those related to photosynthesis, carbon metabolism, and ribosomal function, thereby supporting iron homeostasis and maintaining metabolic balance under stress conditions. Full article

Purpose: We previously reported that the systemic administration of preprogrammed mouse hematopoietic bone marrow-derived progenitor cells (HSPCs) improved visual function and restored a functional retinal pigment epithelial (RPE) layer. Here, we investigated the potential impact of donor vs. host age on systemic cellular therapy in a murine model of retinal degeneration. Methods: HSPCs from young (8 weeks) and old (15 months) mice were programmed ex vivo with a lentiviral vector expressing the RPE65 gene (LV-RPE65) and systemically administering into young or old SOD2 KD mice. Visual loss and pathological changes were evaluated by electroretinogram (ERG), optical coherence tomography (OCT), histology, and immunohistochemistry. Results: Old donor HSPCs administered to old manganese superoxide dismutase (SOD2) knockdown (KD) recipient mice offered the least benefit. This was exemplified by the reduced recruitment and incorporation of LV-RPE65 HSPC into the RPE layer, as well as decreased improvement in visual function, retinal thinning, and limited reduction in oxidative damage and microglial activation. LV-RPE65 HSPC from young mice incorporated into the RPE layer of old SOD2 KD mice, though to a lesser extent than young cells administered to young hosts, offered some level of protection. By contrast, LV-RPE65 HSPCs from old mice, located to the subretinal space of young host mice, reduced visual loss, although some retinal pathology was observed. Conclusions: The administration of LV-RPE65 HSPC from old donors to old SOD2 KD mice offered the least improvement. Translational Relevance: Our findings highlight how both donor and recipient age impact the success of HSPC-based retinal therapy and using cells from aged donors for AMD treatment may have some limitations. Full article

Mitochondrial oxidative stress and neuroinflammation are involved in the onset and progression of Alzheimer’s disease (AD). Novel reliable, circulating biomarkers related to these processes were searched in cerebrospinal fluid (CSF) and plasma samples. Paired CSF and plasma samples from 20 subjective memory complaints (SMC) subjects, 20 mild cognitive impairment (MCI) due to AD subjects, and 20 Alzheimer’s dementia (ADd) patients were analyzed. Protein amounts of manganese-containing superoxide dismutase 2 (SOD2), cell-free mitochondrial DNA (cf-mtDNA) level, DNase I, and matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) activities were determined. As for SOD2, an MCI male-specific significant increase in both biofluids and an ADd male-specific significant decrease in plasma were found. No significant differences were demonstrated in cf-mtDNA level. An ADd-specific significant increase in plasma DNase I and MMP-2 activities was found. A SMC female-specific significant higher value in CSF MMP-9 activity in comparison to male counterparts was demonstrated. The present results suggest a male patient-specific (MCI and ADd) regulation of SOD2 expression in plasma and support an ADd-specific increase in plasma DNase I and MMP-2 activities. Therefore, the potential of SOD2 amount, DNase I, and MMP-2 activities in plasma as new markers of ADd should be explored. The SMC female-specific high activity of MMP-9 might contribute to AD female-sex bias. Full article

Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene. While hepatic manifestations are frequent, psychiatric symptoms occur in up to 30% of patients and may precede neurological signs. This study was the first to assess the relationship between oxidative stress, selected genetic polymorphisms, and psychiatric symptoms in WD. A total of 464 patients under the care of the Institute of Psychiatry and Neurology in Warsaw were studied. Genotyping for GPX1 (rs1050450), SOD2 (rs4880), and CAT (rs1001179) was performed, along with biochemical analyses of copper metabolism, oxidative DNA, lipid and protein damage, and systemic antioxidant capacity. Among the most important observations are the following: the homozygous GPX1 rs1050450 TT and SOD2 rs4880 CC genotypes were associated with the lowest prevalence of psychiatric symptoms. The CAT rs1001179 TT genotype was linked to a delayed onset of psychiatric symptoms by 6.0–8.5 years. Patients with or without psychiatric symptoms did not differ significantly in saliva 8-OHdG, total antioxidant capacity, serum glutathione (GSH), catalase, and MnSOD; however, patients reporting psychiatric symptoms had significantly higher prostaglandin F2α 8-epimer (8-iso-PGF2α) concentrations and tended to have lower serum glutathione peroxidase (Gpx) concentrations compared to those without such symptoms. Our data firstly provide consistent evidence that oxidative stress balance associated with copper overload in the CNS may be associated with CNS damage and the development of psychiatric symptoms of WD. In particular, our findings of increased oxidative lipid damage together with decreased Gpx activity indirectly suggest that damage to neuronal membrane lipids, which may be potentially related to abnormalities in GSH metabolism, may have an etiological role in CNS damage and related symptoms. Full article

Manganese superoxide dismutase (MnSOD) is a vital mitochondrial antioxidant enzyme that preserves cellular integrity by catalyzing the dismutation of superoxide radicals into hydrogen peroxide. Its central role in maintaining redox homeostasis has positioned it as a key target in biomedical research. This review provides an in-depth examination of MnSOD’s structural and functional properties, regulatory mechanisms, and its involvement in the pathogenesis of various human diseases. Full article

This study evaluated the effects of organic trace mineral supplementation on growth performance, antioxidant indices, mineral status, and diarrhea incidence in dairy calves raised in arid climates. Twenty-five male Holstein calves were randomly assigned to five dietary treatments for 21 days, as follows: (1) control group (no organic mineral supplementation), (2) copper-methionine (Cu-Met) supplemented diet, (3) zinc-methionine (Zn-Met) supplemented diet, (4) manganese-methionine (Mn-Met) supplemented diet, and (5) Zn-Met + Cu-Met + and Mn-Met in a premix supplemented diet. Mineral supplementation had no effect on final body weight or average daily gain. However, the concentrations of Zn, Cu, and Mn significantly increased (p < 0.01) in blood and feces of treated animals. The highest blood concentrations of Zn and Mn were observed in calves receiving Zn-Met, while Mn-Met supplementation significantly influenced blood Cu levels. The highest Zn excretion was recorded in calves receiving the organic mineral premix, whereas the highest Mn and Cu excretion was observed in the Cu-Met group. Additionally, mineral supplementation enhanced total antioxidant capacity and superoxide dismutase activity in plasma samples (p < 0.01). These findings suggest that organic mineral supplementation could be an effective strategy to improve mineral bioavailability and support the health of dairy calves during early life in arid climates. Full article

Soybean is one of the main agricultural commodities, and its productivity is limited by several diseases, such as anthracnose, which is caused by a complex of fungal species, with Colletotrichum truncatum being the most prevalent. Management is mainly carried out through chemical seed treatment. However, a reduction in the sensitivity of C. truncatum to fungicides was observed. Therefore, it is extremely important to search for products that are effective in controlling the disease. The objectives of this study were to evaluate the efficacy of commercial formulations of copper, potassium, manganese, and zinc phosphites in the treatment of soybean seeds infected by C. truncatum, as well as their direct fungitoxicity and ability to induce soybean defense mechanisms. For this purpose, seeds inoculated with C. truncatum were subjected to phosphites and a fungicide (carbendazim + thiram). The seeds were exposed to germination, health, and vigor tests. Fungal toxicity and the ability of phosphites to induce defense through the activities of catalase, peroxidase, and superoxide dismutase enzymes, as well as the levels of lignin and total soluble phenols, were also evaluated. Mn and Zn phosphites showed direct toxicity to C. truncatum and were as effective as the fungicide (carbendazim + thiram) in treating soybean seeds infected by the fungus. Mn phosphite induced the production of catalase (CAT), peroxidase (POX) and lignin, while Zn phosphite increased the production of CAT and POX. These results demonstrate the efficacy of Mn and Zn phosphites in controlling C. truncatum in infected soybean seeds, their direct toxic action, and their ability to induce resistance. Full article

Manganese (Mn) is an essential trace element and a cofactor for several key enzymes, such as mitochondrial superoxide dismutase. Consequently, it plays an important defense role against reactive oxygen species. Despite this, Mn chronic overexposure can result in a neurological disorder referred to as manganism, which shares some similarities with Parkinson’s disease. Mn levels seem regulated by many transporters responsible for its uptake and efflux. These transporters play an established role in many inherited disorders of Mn metabolism and neurotoxicity. Some inherited Mn metabolism disorders, caused by mutations of SLC30A10 and SLC39A14, assume crucial importance since earlier treatment results in a better prognosis. Physicians should be familiar with the clinical presentation of these disorders as the underlying cause of dystonia/parkinsonism and look for other accompanying features, such as liver disease and polycythemia, which are typically associated with SLC30A10 mutations. This review aims to highlight the currently known Mn transporters, Mn-related neurotoxicity, and its consequences, and it provides an overview of inherited and acquired disorders of Mn metabolism. Currently available treatments are also discussed, focusing on the most frequently encountered presentations. Full article

Rheumatoid arthritis (RA) is a long-term systemic autoimmune disorder that causes joint inflammation, swelling, pain, bone erosion, and deformities. Recent findings emphasize the anti-inflammatory and antioxidant properties of bioactive natural compounds, such as polyphenols extracted from plants and fruits, and their possible synergistic effect when used in combination with current therapies to improve the prognosis and symptoms of inflammatory rheumatic diseases. Here, we report that Sicilian extra virgin olive oil polyphenol-enriched extracts (PE-EVOOs) reduce intracellular reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), in peripheral mononuclear cells (PBMCs) obtained from both RA patients and healthy subjects (HSs) treated with lipopolysaccharides (LPS) as a control. HPLC-ESI-MS analysis highlighted that PE-EVOOs are rich in different polyphenolic compounds responsible for many of the observed biological effects. At molecular levels, Western blotting analyses revealed that PE-EVOO treatment is associated with the downregulation of the phosphorylated and active form of the inflammatory transcription factor NF-κB and the pro-inflammatory enzyme cyclooxygenase 2 (COX2). In addition, PE-EVOOs upregulated the transcription factor Nrf2 and its target antioxidant enzyme catalase and manganese superoxide dismutase (MnSOD). Collectively, these results suggest a possible use of PE-EVOOs as potential adjuvants for the treatment of RA. Full article

Ionizing radiation is a health threat to many, including warfighters, radiological emergency responders, radiotherapy patients, and astronauts. Despite this, no FDA-approved prophylactic medical countermeasures exist to attenuate the symptoms that occur from radiation exposure. Manganese has recently been shown to be critical for radioresistance in a wide range of organisms. In this study, we designed a stringent feeding method to test the prophylactic effects of dietary manganese on Drosophila’s lifespan before exposure to acute irradiation. We found that male flies have substantially lower radioresistance than females, but feeding with low doses of MnCl₂ before acute irradiation exposure extends male survival to that of females. Whole animal electron paramagnetic resonance analyses showed males have lower amounts of high-symmetry manganese-metabolite antioxidant complexes (H-Mn) than females, but manganese supplementation increases H-Mn to female levels. Levels of mitochondrial free-radical scavenger manganese-superoxide-dismutase 2 (MnSOD2) did not increase after acute irradiation, nor did loss of MnSOD2 sensitize larvae to acute irradiation exposure. These data support that prophylactic manganese feeding is sufficient to increase survivorship in males subjected to acute irradiation, independent of MnSOD2 levels, indicating a role of antioxidant manganese-metabolite H-Mn complexes for radioprotection. Furthermore, this Drosophila feeding method could be used to identify additional radiation countermeasures. Full article

Aluminum (Al) toxicity in acidic soils poses significant challenges to crop growth and development. However, the response mechanism of Shatian pomelo (Citrus maxima ‘Shatian Yu’) roots to Al toxicity remains poorly understood. This study employed root phenotype analysis, physiological response index measurement, root transcriptome analysis, and quantitative PCR (qPCR) validation to investigate the effects of Al toxicity on Shatian pomelo roots. The findings revealed that Al toxicity inhibited root growth and development, resulting in reduced root biomass, total root length, total root surface area, root volume, average root diameter, and root tip count. Antioxidant enzyme activities (peroxidase, superoxide dismutase, ascorbate peroxidase, and catalase activity) and soluble protein content increased with rising Al toxicity, whereas malondialdehyde content initially increased and then declined. Additionally, Al toxicity stress increased Al (1439.25%) content and decreased boron (B, 50.64%), magnesium (Mg, 42.04%), calcium (Ca, 46.02%), manganese (Mn, 86.75%), and iron (Fe, 69.92%) levels in the roots. RNA sequencing (RNA-seq) analysis identified 3855 differentially expressed genes (DEGs) between 0 mmol/L Al (control) and 4 mmol/L Al (Al toxicity) concentrations, with 1457 genes up-regulated and 2398 down-regulated, indicating a complex molecular regulatory response. The qPCR results further validated these findings. This study elucidates the response mechanisms of Shatian pomelo roots to Al toxicity stress, providing insights into the regulatory pathways involved. The findings offer valuable reference points for breeding Al-resistant Shatian pomelo varieties. The results of this study provide important genetic tools and technical support for the screening and breeding of highly resistant varieties of Shatian pomelo. On the one hand, by detecting the key indexes (such as antioxidant enzyme activity and nutrient absorption capacity) of Shatian pomelo, varieties with excellent anti-Al toxicity characteristics can be selected. On the other hand, the Al-resistant genes identified in this study, such as TFM1 and ALERTFA0, can be used to develop molecular markers, assisted marker breeding, or transgenic breeding to accelerate the breeding process of Al-resistant strains. Full article