Oxidative Addition of Aryl Halides to a Ni(I)-Bipyridine Complex

The oxidative addition of aryl halides to bipyridine- or phenanthroline-ligated nickel(I) is a commonly proposed step in nickel catalysis. However, there is a scarcity of complexes of this type that both are well-defined and undergo oxidative addition with aryl halides, hampering organometallic studies of this process. We report the synthesis of a well-defined Ni(I) complex, [(CO2Etbpy)NiCl]4 (1). Its solution-phase speciation is characterized by a significant population of monomer and a redox equilibrium that can be perturbed by π-acceptors and σ-donors. 1 reacts readily with aryl bromides, and mechanistic studies are consistent with a mechanism proceeding through an initial Ni(I) → Ni(III) oxidative addition. Such a process was demonstrated stoichiometrically for the first time, affording a structurally characterized Ni(III) aryl complex.

Vitamin D Prevents High Glucose-Induced Lipid Droplets Accumulation in Cultured Endothelial Cells: The Role of Thioredoxin Interacting Protein

Vitamin D (VitD) exerts protective effects on the endothelium, which is fundamental for vascular integrity, partly by inhibiting free radical formation. We found that VitD prevents high glucose-induced Thioredoxin Interacting Protein (TXNIP) upregulation. Increased amounts of TXNIP are responsible for the accumulation of reactive oxygen species and, as a consequence, of lipid droplets. This is associated with increased amounts of triglycerides as the result of increased lipogenesis and reduced fatty acid oxidation. Remarkably, VitD rebalances the redox equilibrium, restores normal lipid content, and prevents the accumulation of lipid droplets. Our results highlight TXNIP as one of the targets of VitD in high glucose-cultured endothelial cells and shed some light on the protective effect of VitD on the endothelium.

Elucidating the Neuroprotective Role of PPARs in Parkinson’s Disease: A Neoteric and Prospective Target

One of the utmost frequently emerging neurodegenerative diseases, Parkinson’s disease (PD) must be comprehended through the forfeit of dopamine (DA)-generating nerve cells in the substantia nigra pars compacta (SN-PC). The etiology and pathogenesis underlying the emergence of PD is still obscure. However, expanding corroboration encourages the involvement of genetic and environmental factors in the etiology of PD. The destruction of numerous cellular components, namely oxidative stress, ubiquitin-proteasome system (UPS) dysfunction, autophagy-lysosome system dysfunction, neuroinflammation and programmed cell death, and mitochondrial dysfunction partake in the pathogenesis of PD. Present-day pharmacotherapy can alleviate the manifestations, but no therapy has been demonstrated to cease disease progression. Peroxisome proliferator-activated receptors (PPARs) are ligand-directed transcription factors pertaining to the class of nuclear hormone receptors (NHR), and are implicated in the modulation of mitochondrial operation, inflammation, wound healing, redox equilibrium, and metabolism of blood sugar and lipids. Numerous PPAR agonists have been recognized to safeguard nerve cells from oxidative destruction, inflammation, and programmed cell death in PD and other neurodegenerative diseases. Additionally, various investigations suggest that regular administration of PPAR-activating non-steroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, indomethacin), and leukotriene receptor antagonists (montelukast) were related to the de-escalated evolution of neurodegenerative diseases. The present review elucidates the emerging evidence enlightening the neuroprotective outcomes of PPAR agonists in in vivo and in vitro models experiencing PD. Existing articles up to the present were procured through PubMed, MEDLINE, etc., utilizing specific keywords spotlighted in this review. Furthermore, the authors aim to provide insight into the neuroprotective actions of PPAR agonists by outlining the pharmacological mechanism. As a conclusion, PPAR agonists exhibit neuroprotection through modulating the expression of a group of genes implicated in cellular survival pathways, and may be a propitious target in the therapy of incapacitating neurodegenerative diseases like PD.

OCT4 Represses Inflammation and Cell Injury During Orchitis by Regulating CIP2A Expression

Octamer-binding transcription factor 4 (OCT4) and cancerous inhibitor of protein phosphatase 2A (CIP2A) are upregulated in testicular cancer and cell lines. However, its contribution to orchitis (testicular inflammation) is unclear and was thus, investigated herein. Cell-based experiments on a lipopolysaccharide (LPS)-induced orchitis mouse model revealed robust inflammation, apoptotic cell death, and redox disorder in the Leydig (interstitial), Sertoli (supporting), and, germ cells. Meanwhile, real-time quantitative PCR revealed low OCT4 and CIP2A levels in testicular tissue and LPS-stimulated cells. A gain-of-function study showed that OCT4 overexpression not only increased CIP2A expression but also repressed LPS-induced inflammation, apoptosis, and redox disorder in the aforementioned cells. Furthermore, the re-inhibition of CIP2A expression by TD-19 in OCT4-overexpressing cells counteracted the effects of OCT4 overexpression on inflammation, apoptosis, and redox equilibrium. In addition, our results indicated that the Keap1-Nrf2-HO-1 signaling pathway was mediated by OCT4 and CIP2A. These findings provide insights into the potential mechanism underlying OCT4- and CIP2A-mediated testicular inflammation.

Protective Effects of Purple Rice Husk against Diabetic Nephropathy by Modulating PGC-1α/SIRT3/SOD2 Signaling and Maintaining Mitochondrial Redox Equilibrium in Rats

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease worldwide. Oxidative stress and mitochondrial dysfunction are central to its pathogenesis. Rice husk, the leftover from the milling process, is a good source of phytochemicals with antioxidant activity. This study evaluated the possible protection of purple rice husk extract (PRHE) against diabetic kidney injury. Type 2 diabetic rats were given vehicle, PRHE, metformin, and PRHE+metformin, respectively, while nondiabetic rats received vehicle. After 12 weeks, diabetic rats developed nephropathy as proven by metabolic alterations (increased blood glucose, insulin, HOMA-IR, triglycerides, cholesterol) and renal abnormalities (podocyte injury, microalbuminuria, increased serum creatinine, decreased creatinine clearance). Treatment with PRHE, metformin, or combination diminished these changes, improved mitochondrial function (decreased mitochondrial swelling, reactive oxygen species production, membrane potential changes), and reduced renal oxidative damage (decreased lipid peroxidation and increased antioxidants). Increased expression of PGC-1α, SIRT3, and SOD2 and decreased expression of Ac-SOD2 correlated with the beneficial outcomes. HPLC revealed protocatechuic acid and cyanidin-3-glucoside as the key components of PRHE. The findings indicate that PRHE effectively protects against the development of DN by retaining mitochondrial redox equilibrium via the regulation of PGC-1α-SIRT3-SOD2 signaling. This study creates an opportunity to develop this agricultural waste into a useful health product for diabetes.

Effects of different models of sucrose intake on the oxidative status of the uterus and ovary of rats

The aim of the study was to assess the effect of different models of sucrose intake on carbohydrate-lipid metabolism and changes in oxidant balance in the ovaries and uterus of rats. Animals were divided into three groups: I—basic feed, II—feed contains 8% of sucrose, III—alternately every second week the basic feed and modified feed contains 16% of sucrose. The diet containing 8% of sucrose was found to result in an increased activity of antioxidant enzymes in the blood, with unchanged malonylodialdehyde concentration. Variable sucrose administration pattern intensified oxidative stress in the blood and led to disturbed redox equilibrium in the rat uterus, even at a comparable long-term sucrose uptake as in the group II. This was manifested as a reduced superoxide dismutase activity (in the blood and uterus) and a higher malonylodialdehyde concentration (in the uterus). The changes observed could have been a result of metabolic disorders (higher amount of visceral fat, higher glucose concentration, higher index of homeostasis model assessment of insulin resistance, and reduced HDL-cholesterol concentration) and endocrine disorders (higher oestrogen concentrations). Changes in the antioxidant status in the rats kept on the alternating diet, may underpin the failure of fertilised egg implantation in the uterine tissue and pregnancy completion.

The Treatment of Acid Mine Drainage Using Vertically Flowing Wetland: Insights into the Fate of Chemical Species

In this study, the treatment of acid mine drainage (AMD) using vertically flowing wetland was explored. The wetland was enriched with Vetiveria zizanioides as a decontaminating media and soil as the substrate. Water was percolated through the substrate and the throughput samples were collected and characterized every five days for a period of 30 days. The obtained results revealed a tolerant index of 1.03 for Vetiveria zizanioides, and a net reduction of metals and sulfate. The removal efficacy of chemical species was observed to obey the following order: Fe (71.25%) > Zn (70.40%) > Mn (62%) > Al (56.68%)> SO42− (55.18%) > Ni (35%) > Cu (18.83%). The removal of chemical species was further aided by the used substrate, and this could be attributed to the accumulation of chemical species on the soil through precipitation, adsorption, and phyto-retention. As such, it could be deduced that the substrate plays a significant role in the removal of metals, while the grass and external factors accounted for the rest of the chemical species attenuation. The translocation assessment revealed that the distribution of chemical species was observed to be predominant in the roots, except manganese, which was transferred in the shoot (67%). The XRF, XRD, FTIR, and SEM-EDS analysis revealed the presence of AMD chemical species in the substrate and the grass components, hence confirming that the plants are playing a huge role in the removal of contaminants from AMD. The PH REdox EQuilibrium (in C language) (PHREEQC) geochemical model confirm that metals existed as di-and-trivalent complexes in AMD. Lastly, available metals were precipitated as metals hydroxides and oxy-hydrosulfates by the substrate. In light of the obtained results, vertically flowing wetland could be used for the passive treatment of AMD, and it will play a huge role in active and abandoned mines. However, prolonged assessment should be undertaken to understand its performance over a notable period of time.

Effects of Acupuncture on Oxidative Stress Amelioration via Nrf2/ARE-Related Pathways in Alzheimer and Parkinson Diseases

Oxidative stress is responsible for the pathogeneses of various diseases. Mitochondrial dysfunction, impaired DNA repair, and cellular damage followed by oxidative stress contribute to neurodegenerative diseases, such as Alzheimer disease (AD) and Parkinson disease (PD). Acupuncture is a traditional therapy that has been practiced for >3000 years in Asia. Many studies have demonstrated that acupuncture has notable antioxidative, anti-inflammatory, and antiapoptotic effects. However, the exact mechanism remains unclear. Nuclear factor erythroid 2-related factor (Nrf2) is crucial in regulating the redox equilibrium. Activated Nfr2 translocates into the nucleus, binds to the antioxidant response element (ARE), and initiates antioxidative enzyme transcription. In this review, we demonstrated the effects of acupuncture on oxidative stress amelioration in AD and PD animal models through Nrf2/ARE pathway activation and Nrf2/ARE-related pathway regulation. Thus, acupuncture could be a therapeutic option for AD and PD.

Contribution of Adipose Tissue Oxidative Stress to Obesity-Associated Diabetes Risk and Ethnic Differences: Focus on Women of African Ancestry

Adipose tissue (AT) storage capacity is central in the maintenance of whole-body homeostasis, especially in obesity states. However, sustained nutrients overflow may dysregulate this function resulting in adipocytes hypertrophy, AT hypoxia, inflammation and oxidative stress. Systemic inflammation may also contribute to the disruption of AT redox equilibrium. AT and systemic oxidative stress have been involved in the development of obesity-associated insulin resistance (IR) and type 2 diabetes (T2D) through several mechanisms. Interestingly, fat accumulation, body fat distribution and the degree of how adiposity translates into cardio-metabolic diseases differ between ethnicities. Populations of African ancestry have a higher prevalence of obesity and higher T2D risk than populations of European ancestry, mainly driven by higher rates among African women. Considering the reported ethnic-specific differences in AT distribution and function and higher levels of systemic oxidative stress markers, oxidative stress is a potential contributor to the higher susceptibility for metabolic diseases in African women. This review summarizes existing evidence supporting this hypothesis while acknowledging a lack of data on AT oxidative stress in relation to IR in Africans, and the potential influence of other ethnicity-related modulators (e.g., genetic-environment interplay, socioeconomic factors) for consideration in future studies with different ethnicities.

Quantification of Intracellular Thiols by HPLC-Fluorescence Detection

Biothiols, such as cysteine and glutathione, play important roles in various intracellular reactions represented by the redox equilibrium against oxidative stress. In this study, a method for intracellular thiol quantification using HPLC-fluorescence detection was developed. Thiols were derivatized with a thiol-specific fluorescence derivatization reagent, viz. ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (SBD-F), followed by reversed-phase separation on an InertSustain AQ-C18 column. Six different SBD-thiols (homocysteine, cysteine, cysteinylglycine, γ-glutamylcysteine, glutathione, and N-acetylcysteine as an internal standard) were separated within 30 min using a citric buffer (pH 3.0)/MeOH mobile phase. The calibration curves of all the SBD-thiols had strong linearity (R2 > 0.999). Using this developed method, the thiol concentrations of human chronic myelogenous leukemia K562 cell samples were found to be 5.5–153 pmol/1 × 106 cells. The time-dependent effect of a thiol scavenger, viz. N-ethyl maleimide, on intracellular thiol concentrations was also quantified. This method is useful for elucidating the role of intracellular sulfur metabolism.