Redox Report最新文献

Ferroptosis is an emerging and novel type of iron-dependent programmed cell death which is mainly caused by the excessive deposition of free intracellular iron in the brain cells. This deposited free iron exerts a ferroptosis pathway, resulting in lipid peroxidation (LiPr). There are mainly three ferroptosis pathways viz. iron metabolism-mediated cysteine/glutamate, and LiPr-mediated. Iron is required by the brain as a redox metal for several physiological activities. Due to the iron homeostasis balance disruption, the brain gets adversely affected which further causes neurodegenerative diseases (NDDs) like Parkinson's and Alzheimer's disease, strokes, and brain tumors like glioblastoma (GBS), and glioma. Nanotechnology has played an important role in the prevention and treatment of these NDDs. A synergistic effect of nanomaterials and ferroptosis could prove to be an effective and efficient approach in the field of nanomedicine. In the current review, the authors have highlighted all the latest research in the field of ferroptosis, specifically emphasizing on the role of major molecular key players and various mechanisms involved in the ferroptosis pathway. Moreover, here the authors have also addressed the correlation of ferroptosis with the pathophysiology of NDDs and theragnostic effect of ferroptosis and nanomaterials for the prevention and treatment of NDDs.

Objectives: This review outlines the function of oxidative stress in DR and discusses therapeutic strategies to treat DR with antioxidants.

Methods: Published papers on oxidative stress in DR and therapeutic strategies to treat DR with antioxidants were collected and reviewed via database searching on PubMed.

Results: The abnormal development of DR is a complicated process. The pathogenesis of DR has been reported to involve oxidative stress, despite the fact that the mechanisms underlying this are still not fully understood. Excessive reactive oxygen species (ROS) accumulation can damage retina, eventually leading to DR. Increasing evidence have demonstrated that antioxidant therapy can alleviate the degeneration of retinal capillaries in DR.

Conclusion: Oxidative stress can play an important contributor in the pathogenesis of DR. Furthermore, animal experiments have shown that antioxidants are a beneficial therapy for treating DR, but more clinical trial data is needed.

Objective: Methotrexate (MTX) is a drug used in the treatment of cancer and autoimmune disorders; however, its clinical use is limited because of serious side effects including renal toxicity. This study aimed to investigate the protective effect of Lmethionine (L-Met) on MTX toxicity in the kidneys of rats.Methods: Thirty male rats were divided equally into five groups: control (saline), Met400 (400 mg/kg L-Met), MTX (20 mg/kg MTX), MTX-Met300 (300 mg/kg L-Met and 20 mg/kg MTX), and MTX-Met400 (400 mg/kg L-Met and 20 mg/kg MTX). Rats were euthanized one day after the last dose administration (day 16) and serum and renal tissue samples were collected. Renal function and injury indices, oxidative stress/antioxidant indices and proinflammatory cytokines were evaluated.Results: The results showed that L-Met could effectively counteract the nephrotoxic effects of MTX, in a dose-related manner, by improving most of the tested parameters. Furthermore, the higher dose of L-Met was able to restore several parameters to normal levels. In addition, investigation of MTX-induced hematological changes revealed a corrective potential of L-Met.Conclusion: L-Met can be an effective adjuvant therapy to modulate renal toxicity associated with MTX because of its antioxidant and antiinflammatory effects.

Objective: The testis is vulnerable to ionizing radiation, sexual dysfunction and male infertility are common problems after local radiation or whole-body exposure. Currently, there are no approved drugs for the prevention or treatment of radiation testicular injury. Sulforaphane (SFN) is an indirect antioxidant that induces phase II detoxification enzymes and antioxidant genes. Herein, we investigated the radiation protective effect of SFN on testicular injury in mice and its potential mechanism.

Materials and methods: Mice were randomly divided into blank control group (Ctrl), radiation + no pretreatment group (IR), and radiation + SFN groups (IRS). In the radiation + SFN groups, starting from 72 h before radiation, SFN solution was intraperitoneally injected once a day until they were sacrificed. Mice in the blank control group and the radiation + no pretreatment group were simultaneously injected intraperitoneally with an equal volume of the solvent used to dissolve SFN (PBS with a final concentration of 0.1%DMSO) until they were sacrificed. They were subjected to 6Mev-ray radiation to the lower abdominal testis area (total dose 2Gy). Twenty-four hours after radiation, six mice in each group were randomly sacrificed. Seventy-two hours after radiation, the remaining mice were sacrificed.

Results: The results showed that the harmful effects of ionizing radiation on testes were manifested as damage to histoarchitecture, increased oxidative stress, and apoptosis, and thus impaired male fertility. SFN injections can reverse these symptoms.

Conclusions: The results showed that SFN can improve the damage of mouse testis caused by irradiation. Furthermore, SFN prevents spermatogenesis dysfunction caused by ionizing radiation by activating Nrf2 and its downstream antioxidant gene.

Background: Nucleolin is a multifunctional nucleolar protein with RNA-binding properties. Increased nucleolin expression protects cells from H₂O₂-induced damage, but the mechanism remains unknown. Long noncoding RNAs (lncRNAs) play crucial roles in cardiovascular diseases. However, the biological functions and underlying mechanisms of lncRNAs in myocardial injury remain unclear.Methods: In a nucleolin-overexpressing cardiac cell line, high-throughput technology was used to identify lncRNAs controlled by nucleolin. Cell counting kit-8 assay was used to determine cell viability, lactate dehydrogenase (LDH) assay to detect cell death, caspase activity assay and propidium iodide staining to confirm cell apoptosis, and RNA immunoprecipitation to examine the interaction between Fendrr and nucleolin.Results: We found that Fendrr expression was significantly downregulated in mouse hearts subjected to myocardial ischemia-reperfusion (MI/R) injury. High Fendrr expression abrogated H₂O₂-mediated injury in cardiomyocytes as evidenced by increased cell viability and decreased cell apoptosis. Conversely, Fendrr knockdown exacerbated the cardiomyocytes injury. Also, nucleolin overexpression inhibits Fendrr downregulation in H₂O₂-induced cardiomyocyte injury. Fendrr overexpression significantly reversed the role of the suppression of nucleolin expression in H₂O₂-induced cardiomyocytes.Conclusion: LncRNA Fendrr is involved in the cardioprotective effect of nucleolin against H₂O₂-induced injury and may be a potential therapeutic target for oxidative stress-induced myocardial injury.

Background: The cardiovascular crisis is advancing rapidly throughout the world. A large number of studies have shown that plant polyphenols affect major mechanisms involved in cardiovascular events through their action on the antioxidant system, signaling, and transcription pathways. D-limonene, a monocyclic monoterpene obtained from citrus fruits, is reported to possess many pharmacological activities.Methods: The experiment was designed to determine the protective effect of D-limonene against cardiac injury induced by CCl₄ in Wistar rats. Rats were treated with two doses of D-limonene against cardiac injury induced by CCl₄. Serum toxicity markers, cardiac toxicity biomarker enzymes, inflammatory mediators, anti-oxidant armory, lipid peroxidation, lipid profile, and histology were done.Results: CCl₄ intoxication resulted in a substantial rise in FFA, TC, TG, PL, LDL, VLDL, and a reduction in HDL, restoring these changes with the administration of D-limonene at a dosage of 200 mg/kg. CCl₄ administration also resulted in lipid oxidation and decreased antioxidant activity. At the same time, D-limonene at a dosage of 200 mg/kg body weight inhibited LPO and restored in vivo antioxidant components to normal. CC_l4 intoxication also resulted in a significant increase in inflammatory markers like IL-6, TNF-α, high sensitivity Corticotropin Releasing Factor (Hs-CRF), and biomarkers of cardiac toxicity like alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase MB (CKMB), and Troponin I & troponin-t activities. D-limonene reversed all these changes to normal. Histology further confirmed our obtained results.Conclusion: These findings indicate that D-limonene can ameliorate cardiac injury at a 200 mg/kg body weight dosage. Henceforth, D-Limonene intervenes in mediating CCl₄ induced toxicity by various signaling pathways.

Background: The study was undertaken to evaluate the effect of 6-week supplementation with a daily dose of 2g of curcumin on VO_2max and prooxidant/antioxidant homeostasis in middle-aged amateur long-distance runners during the preparatory period of the macrocycle.

Methods: Thirty runners were randomly assigned to a placebo group (PL) and a curcumin-supplemented group (CU). Their VO_2max was assessed before supplementation and after 6 weeks of supplementation. Venous blood samples were collected from the participants at rest, immediately after exercise, and after 1h of recovery to evaluate the activity of antioxidant enzymes (SOD, CAT, GPx), non-enzymatic antioxidants (GSH, UA) and sirtuin 3 level (SIRT 3), as well as the levels of oxidative stress markers (TOS/TOC, MDA, and 8-OHdG) and muscle damage markers (CK, LDH, and Mb).

Results: VO_2max, the activity of enzymatic antioxidants, the concentrations of non-enzymatic antioxidants, the levels of oxidative stress markers, and the levels of muscle damage markers did not change significantly in the CU group over 6 weeks of supplementation with curcumin. However, the resting concentration of SIRT 3 was found to be significantly higher (p ≤ 0.05) compared with pre-supplementation.

Conclusion: Curcumin supplementation does not have a significant effect on VO_2max and prooxidant/antioxidant homeostasis in runners.

Objective: Psychostimulant use induces oxidative stress and alters redox imbalance, influencing epigenetic signatures in the central nervous system (CNS). Among the various epigenetic changes, DNA methylation is directly linked to oxidative stress metabolism via critical redox intermediates such as NAD+, S-adenosylmethionine (SAM), and 2-oxoglutarate. Fluctuations in these intermediates directly influence epigenetic signatures, which leads to detectable alterations in gene expression and protein modification. This review focuses on recent advances in the impact of psychostimulant use on redox-imbalance-induced DNA methylation to develop novel epigenetics-based early interventions. Methods: This review is based on collective research data obtained from the PubMed, Science Direct, and Medline databases. The keywords used in the electronic search in these databases were redox, substance use disorder, psychostimulants, DNA methylation, and neurological diseases. Results: Instability in DNA methylation levels and redox expression effects are reported in various behavioral models stimulated by psychostimulants and opioids, indicating the widespread involvement of epigenetic changes in DNA methylation signatures in neurological disorders. Discussion: This review summarizes the need for more studies and experimental evaluations of DNA-methylation-based strategies that may help to understand the association between psychostimulant use and oxidative stress or redox-linked metabolic recalibration influencing neuronal impairments.

Objectives: The pathogenesis of vitiligo remains unclear. In this review, we comprehensively describe the role of damage associated molecular patterns (DAMPs) during vitiligo pathogenesis.

Methods: Published papers on vitiligo, oxidative stress and DAMPs were collected and reviewed via database searching on PubMed, MEDLINE and Embase, etc.

Results: Oxidative stress may be an important inducer of vitiligo. At high oxidative stress levels, damage-associated molecular patterns (DAMPs) are released from keratinocytes or melanocytes in the skin and induce downstream immune responses during vitiligo. Treatment regimens targeting DAMPs can effectively improve disease severity.

Discussion: DAMPs play key roles in initiating host defenses against danger signals, deteriorating the condition of vitiligo. DAMP levels in serum and skin may be used as biomarkers to indicate vitiligo activity and prognosis. Targeted therapies, incorporating HMGB1, Hsp70, and IL-15 could significantly improve disease etiology. Thus, novel strategies could be identified for vitiligo treatment by targeting DAMPs.