Genetic Polymorphisms of MnSOD Modify the Impacts of Environmental Melamine on Oxidative Stress and Early Kidney Injury in Calcium Urolithiasis Patients

Environmental melamine exposure increases the risks of oxidative stress and early kidney injury. Manganese superoxide dismutase (MnSOD), glutathione peroxidase, and catalase can protect the kidneys against oxidative stress and maintain normal function. We evaluated whether their single-nucleotide polymorphisms (SNPs) could modify melamine’s effects. A total of 302 patients diagnosed with calcium urolithiasis were enrolled. All patients provided one-spot overnight urine samples to measure their melamine levels, urinary biomarkers of oxidative stress and renal tubular injury. Median values were used to dichotomize levels into high and low. Subjects carrying the T allele of rs4880 and high melamine levels had 3.60 times greater risk of high malondialdehyde levels than those carrying the C allele of rs4880 and low melamine levels after adjustment. Subjects carrying the G allele of rs5746136 and high melamine levels had 1.73 times greater risk of high N-Acetyl-β-d-glucosaminidase levels than those carrying the A allele of rs5746136 and low melamine levels. In conclusion, the SNPs of MnSOD, rs4880 and rs5746136, influence the risk of oxidative stress and renal tubular injury, respectively, in calcium urolithiasis patients. In the context of high urinary melamine levels, their effects on oxidative stress and renal tubular injury were further increased.

Cryotrapping peroxide in the active site of human mitochondrial manganese superoxide dismutase crystals for neutron diffraction

Structurally identifying the enzymatic intermediates of redox proteins has been elusive due to difficulty in resolving the H atoms involved in catalysis and the susceptibility of ligand complexes to photoreduction from X-rays. Cryotrapping ligands for neutron protein crystallography combines two powerful tools that offer the advantage of directly identifying hydrogen positions in redox-enzyme intermediates without radiolytic perturbation of metal-containing active sites. However, translating cryogenic techniques from X-ray to neutron crystallography is not straightforward due to the large crystal volumes and long data-collection times. Here, methods have been developed to visualize the evasive peroxo complex of manganese superoxide dismutase (MnSOD) so that all atoms, including H atoms, could be visualized. The subsequent cryocooling and ligand-trapping methods resulted in neutron data collection to 2.30 Å resolution. The P6122 crystal form of MnSOD is challenging because it has some of the largest unit-cell dimensions (a = b = 77.8, c = 236.8 Å) ever studied using high-resolution cryo-neutron crystallography. The resulting neutron diffraction data permitted the visualization of a dioxygen species bound to the MnSOD active-site metal that was indicative of successful cryotrapping.

Effects of Manganese Hydroxychloride on Growth Performance, Antioxidant Capacity, Tibia Parameters and Manganese Deposition of Broilers

This study was conducted to investigate the effects of dietary supplementation with manganese hydroxychloride (MHC) on production performance, antioxidant capacity, tibial quality, and manganese (Mn) deposition of broilers. A total of 756 one-day-old male Arbor Acres broilers were randomly allotted to 7 treatments of 6 replicates with 18 broilers per replicate. Broilers were fed corn-soybean meal basal diets supplemented of 100 mg/kg Mn as Mn sulfate (MnSO4), or 0, 20, 40, 60, 80, 100 mg/kg Mn as MHC for 42 days. The growth performance of broilers was not affected by dietary MnSO4 or MHC (p > 0.05), whereas the dressing percentage increased linearly (p < 0.05) with increasing of dietary MHC addition level. The activities of catalase (CAT) and manganese superoxide dismutase (MnSOD), and total antioxidant capability (T-AOC) in serum and liver on day 42 increased linearly (p < 0.05) with increasing of dietary MHC level, while malondialdehyde (MDA) concentration reduced linearly (p < 0.05). The length, strength, and density index of tibia increased linearly (p < 0.05) on day 21 as MHC supplementation level increased; there were no differences between MnSO4 group and 40–100 mg/kg Mn as MHC groups in tibial parameters of broilers (p > 0.05). As supplemental MHC levels increased, the Mn contents in heart, liver, kidney, and tibia increased linearly on day 42 (p < 0.05). In summary, dietary supplementation with MHC improved antioxidant capacity, bone quality, and Mn contents in broilers, but no effects on growth performance were detected. Based on the results of this study, dietary inclusion of 50–90 mg/kg Mn in the form of MHC to broilers is recommended.

Re-Print- Artificial Respiration in Severe COVID-19 Cases: A Beneficial or Deleterious Treatment

The world over artificial respiration is employed as one of the intensive care treatment measures in severe cases of COVID-19 because of the significant respiratory distress patients develop. Nevertheless, the outcome is poor. Lethality varies from country to country and clinic to clinic between 50% and 90%. So the question arises as to whether the use of oxygen can be a risk factor in the treatment of acute inflammatory diseases in general and of COVID-19 in particular. Oxidative stress is the first and oldest step of cellular defense and starts before the activation of the immune system. This leads to an increase of intracellular oxygen in the mitochondria, followed by an elevated electron flow and the formation of superoxide as well as other reactive oxygen species and reactive nitrogen species. Superoxide reacts with nitric oxide, which is always present in inflammation, forming peroxynitrite, the strongest inducer of oxidative stress. This step induces the activation of nuclear factor kB, followed by the production of proinflammatory cytokines. The elevated levels of inducible nitric oxide synthase keep this cycle running. High amounts of superoxide have to be compensated and catabolized by manganese-superoxide dismutase 2 into hydrogen peroxide and in a second step by catalase into water. When using artificial respiration, these steps are accelerated considerably in the inflamed tissue of the lung, leading to a significant increase of the electron flow as well as an elevation of superoxide, oxidative stress, and water. As SARS-CoV-2 generally induces the production of proteins (and not only those necessary for viral reproduction), the water will remain in the tissue, causing edema and thus a wet lung syndrome associated with a growing oxygen diffusion distance to red blood cells. Ultimately, patients do not suffocate in spite of, but because of, the presence of high levels of oxygen. The limited number of patients who survive this deleterious treatment describe it as having had a sensation of drowning. The reasons will be discussed.

The protective effect of manganese superoxide dismutase from thermophilic bacterium HB27 on hydrochloric acid-induced chemical cystitis in rats

Purpose To evaluate the effects of manganese superoxide dismutase (Mn-SOD) from thermophilic bacterium HB27 (name as Tt-SOD) on chemical cystitis. Methods Control and experimental rats were infused by intravesical saline or hydrochloric acid (HCl) on the first day of the experiments. Saline, sodium hyaluronate (SH) or Tt-SOD were infused intravesically once a day for three consequent days. On the fifth day, the rats were weighted and sacrificed following a pain threshold test. The bladder was harvested for histological and biochemical analyses. Results Tt-SOD could reduce the bladder index, infiltration of inflammatory cells in tissues, serum inflammatory factors and SOD levels, mRNA expression of inflammatory factors in tissues, and increase perineal mechanical pain threshold and serum MDA and ROS levels in HCl-induced chemical cystitis. Furthermore, Tt-SOD alleviated inflammation and oxidative stress by the negative regulation of the NF-κB p65 and p38 MAPK signaling pathway. Conclusions Intravesical instillation of Tt-SOD provides protective effects against HCl-induced cystitis.

281 The Effects of Whole Cottonseed Supplementation on Performance, Breeding Soundness Exams, and Manganese Superoxide Dismutase Concentrations in the Blood and Semen of Beef Bulls

The objective of this research was to determine the effects of whole cottonseed containing gossypol on post-pubertal beef bulls. In a two-year study, 46 Angus and Red Angus bulls (body weight 457.0 ± 85.2 kg; 16 to 20-months of age) were stratified by BW and randomly assigned to 1 of 3 levels of whole cottonseed supplementation while receiving ad libitum roughage. The treatments included: DD (n = 14, control; 3.18 kg/d of dried distillers grain, W/D (n = 16; 1.59 kg/d of whole cottonseed and 1.59 kg/d of dried distillers grain), or WW (n = 16 3.18 kg/d of whole cottonseed). Diets were formulated to be isocaloric and isonitrogenous. In both years, bulls were weighed, administered a breeding soundness exam, and morphological characteristics of spermatozoa were measured on d 0, 28, and 60. In year 1, blood and semen samples were collected on d 0, 28, and 60 to measure manganese superoxide dismutase activity. There was no treatment effect for blood or semen manganese superoxide dismutase concentration (P &gt; 0.255). There was a treatment effect (P &lt; 0.02) for average daily gain as bulls fed WW gained less compared to those fed WD and DD (0.96, 1.23, and 1.39 kg/d, respectively). No treatment effect was observed for scrotal circumference (P &gt; 0.50). There were no treatment × time interactions, treatment, or time main effects for percentages of normal spermatozoa, spermatozoa with coiled or folded tails, or proximal droplets (P &gt; 0.12). There was a treatment effect on the amount of swollen midpiece or abnormal head as bull in the DD treatment had a greater (P &lt; 0.02) percentage of other abnormalities compared to WW, but WD was not different (P &gt; 0.16). Inclusion of whole cottonseed may affect average daily gain, but does not affect reproductive parameters of beef bulls.

Evaluating the expression of key genes involved in resistance to oxidative stress in ALL patients

Background: Leukemia accounts for about 8% of all cancers and causes approximately 7% of mortalities due to malignancies. Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and rare in older subjects. The aim of this study was to evaluate the expression of oxidative stress resistance genes including Catalase, manganese superoxide dismutase (MnSOD), Forkhead Box O3 (Foxo3a), and sirtuin-1 (SIRT1) in ALL patients that may be applied for therapeutic purposes in the future. Materials and Methods: In this observational case-control study, blood samples were drawn from 60 newly diagnosed ALL patients and 10 healthy individuals as a control group. After RNA extraction and cDNA synthesis, real-time polymerase chain reaction (RT-PCR) amplification was performed using specific primers for evaluating the expression of Catalase, MnSOD, Foxo3a, and SIRT1 genes. Results: The expression of all studied genes were significantly higher in ALL patients than in the control group; catalase gene, FOX gene, MnSOD gene, and SIRT1 gene were expressed 4 times (p =0.04), 4.5 times (p =0.001), 2.2 times (p =0.05) and 4.8 (p =0.01) times higher than healthy individuals in the control group respectively. However, no significant relationship between their expression and the stage of the disease and blast percentage was demonstrated (P>0.05). Conclusion: According to these results, the authors believe that the pathways involved in oxidative stress may be one of the most important causes of ALL disease's development and progression. In this regard, targeting the critical genes of these pathways can be considered a potential treatment with fewer side effects.