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Biomedicine & Pharmacotherapy =... Dec 2023Alzheimer's disease (AD) stands as the predominant age-related neurodegenerative disorder, for which efficacious treatment remains elusive. An auspicious avenue for this...
Alzheimer's disease (AD) stands as the predominant age-related neurodegenerative disorder, for which efficacious treatment remains elusive. An auspicious avenue for this disease lies in natural compounds sourced from tranditional medicine and plant origins. Parthenolide (PTN) is a natural product with multiple biological functionsand. Recent investigations have illuminated PTN's protective properties against neurological maladies; however, its potential therapeutic role against AD remains uncharted. This study aims to explore the role of PTN in treating AD. Our in vitro findings underscore PTN's bioactivity, as evidenced by its capacity to curtail apoptosis, reduce reactive oxygen species (ROS) production, and restore mitochondrial membrane potential in PC12 cells. Moreover, PTN treatment demonstrates a capacity to ameliorate deficits in spatial learning and memory in the 3 ×Tg-AD murine model. Notably, PTN's therapeutic efficacy surpasses that of a clinical agent, donepezil. Mechanistically, PTN's neuroprotective effects stem from its adept regulation of the AMPK/GSK3β(ser9)/Nrf2 signaling pathway and protection on neuronal cells from ROS-related apoptosis. Although the molecular target and the pre-clinical evaluations of PTN need to be further explored, this study indicates PTN as a potential agent or lead compound for the drug development against AD.
Topics: Rats; Mice; Animals; Reactive Oxygen Species; NF-E2-Related Factor 2; AMP-Activated Protein Kinases; Glycogen Synthase Kinase 3 beta; Signal Transduction; Alzheimer Disease; Cognitive Dysfunction; Neuroprotective Agents; Neurotoxicity Syndromes; Amyloid beta-Peptides
PubMed: 37992573
DOI: 10.1016/j.biopha.2023.115909 -
Journal of Anesthesia Dec 2023Dexmedetomidine (DEX), a highly selective alpha2-adrenoceptors agonist, is not only a sedative drug used during mechanical ventilation in the intensive care unit but... (Review)
Review
Dexmedetomidine (DEX), a highly selective alpha2-adrenoceptors agonist, is not only a sedative drug used during mechanical ventilation in the intensive care unit but also a cardio-protective drug against ischemia-reperfusion injury (IRI). Numerous preclinical in vivo and ex vivo studies, mostly evaluating the effect of DEX pretreatment in healthy rodents, have shown the efficacy of DEX in protecting the hearts from IRI. However, whether DEX can maintain its cardio-protective effect in hearts with comorbidities such as diabetes has not been fully elucidated. Multiple clinical trials have reported promising results, showing that pretreatment with DEX can attenuate cardiac damage in patients undergoing cardiac surgery. However, evidence of the post-treatment effects of DEX in clinical practice remains limited. In this narrative review, we summarize the previously reported evidence of DEX-induced cardio-protection against IRI and clarify the condition of the hearts and the timing of DEX administration that has not been tested. With further investigations evaluating these knowledge gaps, the use of DEX as a cardio-protective drug could be further facilitated in the management of patients undergoing cardiac surgery and might be considered in a broader area of clinical settings beyond cardiac surgery, including patients with acute myocardial infarction.
Topics: Humans; Dexmedetomidine; Pharmaceutical Preparations; Heart; Reperfusion Injury; Protective Agents
PubMed: 37750978
DOI: 10.1007/s00540-023-03261-w -
Chemico-biological Interactions Aug 2023Di-ethylhexyl phthalate (DEHP) is used as an important plasticizer in a wide range of products such as paints, food packaging, medical devices and children's toys. In... (Review)
Review
Di-ethylhexyl phthalate (DEHP) is used as an important plasticizer in a wide range of products such as paints, food packaging, medical devices and children's toys. In recent years, there has been increasing interest in the toxic effects of DEHP on the male reproductive organs, the testicles. Here, we reviewed the basic pathways of testicular damage caused by DEHP. The mechanism involves oxidative stress, ferroptosis, interfering with hypothalamic-pituitary-gonadal axis (HPGA) and testosterone level. We summarized the protective agents that have been shown to be effective in repairing this type of testicular damage in recent years. This provides a new perspective and direction for future research into the health effects and molecular mechanisms of DEHP.
Topics: Child; Male; Humans; Diethylhexyl Phthalate; Testis; Phthalic Acids; Testicular Diseases; Protective Agents
PubMed: 37257576
DOI: 10.1016/j.cbi.2023.110575 -
International Journal of Molecular... Dec 2023There are extensive studies that confirm the harmful and strong influence of oxidative stress on the skin. The body's response to oxidative stress can vary depending on... (Review)
Review
There are extensive studies that confirm the harmful and strong influence of oxidative stress on the skin. The body's response to oxidative stress can vary depending on the type of reactive oxygen species (ROS) or reactive nitrogen species (RNS) and their metabolites, the duration of exposure to oxidative stress and the antioxidant capacity at each tissue level. Numerous skin diseases and pathologies are associated with the excessive production and accumulation of free radicals. title altered Both categories have advantages and disadvantages in terms of skin structures, tolerability, therapeutic performance, ease of application or formulation and economic efficiency. The effect of long-term treatment with antioxidants is evaluated through studies investigating their protective effect and the improvement of some phenomena caused by oxidative stress. This article summarizes the available information on the presence of compounds used in dermatology to combat oxidative stress in the skin. It aims to provide an overview of all the considerations for choosing an antioxidant agent, the topics for further research and the answers sought in order to optimize therapeutic performance.
Topics: Antioxidants; Dermatology; Oxidative Stress; Reactive Oxygen Species; Free Radicals
PubMed: 38139345
DOI: 10.3390/ijms242417517 -
Mini Reviews in Medicinal Chemistry 2024Oxidative stress has been reported to be involved in the onset and development of several diseases, including neurodegenerative and cardiovascular disorders, some types... (Review)
Review
Oxidative stress has been reported to be involved in the onset and development of several diseases, including neurodegenerative and cardiovascular disorders, some types of cancer, and diabetes. Therefore, finding strategies to detoxify free radicals is an active area of research. One of these strategies is the use of natural or synthetic antioxidants. In this context, melatonin (MLT) has been proven to possess most of the required characteristics of an efficient antioxidant. In addition, its protection against oxidative stress continues after being metabolized, since its metabolites also exhibit antioxidant capacity. Based on the appealing properties of MLT and its metabolites, various synthetic analogues have been developed to obtain compounds with higher activity and lower side effects. This review addresses recent studies with MLT and related compounds as potential antioxidants.
Topics: Melatonin; Antioxidants; Humans; Oxidative Stress; Animals
PubMed: 37366352
DOI: 10.2174/1389557523666230627140816 -
Biomedicine & Pharmacotherapy =... Sep 2023In addition to the anti-diabetic effect of metformin, a growing number of studies have shown that metformin has some exciting properties, such as anti-oxidative... (Review)
Review
In addition to the anti-diabetic effect of metformin, a growing number of studies have shown that metformin has some exciting properties, such as anti-oxidative capabilities, anticancer, genomic stability, anti-inflammation, and anti-fibrosis, which have potent, that can treat other disorders other than diabetes mellitus. We aimed to describe and review the protective and antidotal efficacy of metformin against biologicals, chemicals, natural, medications, pesticides, and radiation-induced toxicities. A comprehensive search has been performed from Scopus, Web of Science, PubMed, and Google Scholar databases from inception to March 8, 2023. All in vitro, in vivo, and clinical studies were considered. Many studies suggest that metformin affects diseases other than diabetes. It is a radioprotective and chemoprotective drug that also affects viral and bacterial diseases. It can be used against inflammation-related and apoptosis-related abnormalities and against toxins to lower their effects. Besides lowering blood sugar, metformin can attenuate the effects of toxins on body weight, inflammation, apoptosis, necrosis, caspase-3 activation, cell viability and survival rate, reactive oxygen species (ROS), NF-κB, TNF-α, many interleukins, lipid profile, and many enzymes activity such as catalase and superoxide dismutase. It also can reduce the histopathological damages induced by many toxins on the kidneys, liver, and colon. However, clinical trials and human studies are needed before using metformin as a therapeutic agent against other diseases.
Topics: Humans; Metformin; Hypoglycemic Agents; Antioxidants; Apoptosis; Liver; Inflammation; Oxidative Stress
PubMed: 37541178
DOI: 10.1016/j.biopha.2023.115263 -
Food and Chemical Toxicology : An... Dec 2023Deoxynivalenol (DON) is one of the most prevalent mycotoxins in feed, which causes organ toxicity in animals. Therefore, reducing DON-induced organ toxicity can now be... (Review)
Review
Deoxynivalenol (DON) is one of the most prevalent mycotoxins in feed, which causes organ toxicity in animals. Therefore, reducing DON-induced organ toxicity can now be accomplished effectively using protective agents. This review provides an overview of multiple studies on a wide range of protective agents and their molecular mechanisms against DON organ toxicity. Protective agents include plant extracts, yeast products, bacteria, peptides, enzymes, H2, oligosaccharides, amino acids, adsorbents, vitamins and selenium. Among these, biological detoxification of DON using microorganisms to reduce the toxicity of DON without affecting the growth performance of pigs may be the most promising detoxification strategy. This paper also evaluates future developments related to DON detoxification and discusses the detoxification role and application potential of protective agents. This paper provides new perspectives for future research and development of safe and effective feed additives.
Topics: Swine; Animals; Trichothecenes; Mycotoxins; Bacteria; Protective Agents; Animal Feed; Food Contamination
PubMed: 37890761
DOI: 10.1016/j.fct.2023.114121 -
Journal of Agricultural and Food... Dec 2023High-fat diets (HFD) could cause obesity, trigger lipid accumulation, and induce oxidative stress and inflammation, leading to kidney damage. This study aimed to...
High-fat diets (HFD) could cause obesity, trigger lipid accumulation, and induce oxidative stress and inflammation, leading to kidney damage. This study aimed to elucidate the protective effects of nuciferine on HFD-caused nephrotoxicity and explore the underlying mechanisms in Kunming mice and palmitic acid-exposed HK-2 cells. In obese mice, nuciferine notably alleviated HFD-induced chronic renal dysfunction and delayed renal fibrosis progression and podocyte apoptosis, as evidenced by the increased expressions of renal function factors BUN, CRE, and UA and the decreased expressions of key protein factors TGF-β1, p-Samd3, Wnt-1, and β-catenin. Nuciferine also effectively attenuated HFD-induced renal lipid accumulation via the AMPK-mediated regulation of FAS and HSL expressions and suppressed inflammation and oxidative stress via the AMPK-mediated Nrf-2/HO-1 and TLR4/MyD88/NF-κB pathways. In addition, consistent with the results of animal experiments, nuciferine remarkably reversed cell damage and attenuated lipid accumulation, inflammation, and oxidative stress in palmitic acid-exposed HK-2 cells through the AMPK-mediated signaling pathway. Therefore, nuciferine could be a new food-derived protective agent to offset obesity and correlative kidney damage.
Topics: Mice; Animals; Antioxidants; AMP-Activated Protein Kinases; Palmitic Acid; Inflammation; Anti-Inflammatory Agents; NF-kappa B; Obesity; Oxidative Stress; Diet, High-Fat
PubMed: 38006352
DOI: 10.1021/acs.jafc.3c05735 -
European Journal of Pharmacology Oct 2023Cerebral ischemia/reperfusion injury (CIRI) seriously threatens human life and health. Scutellarin (Scu) exhibits neuroprotective effects, but little is known about its...
Cerebral ischemia/reperfusion injury (CIRI) seriously threatens human life and health. Scutellarin (Scu) exhibits neuroprotective effects, but little is known about its underlying mechanism. Therefore, we explored its protective effect on CIRI and the underlying mechanism. Our results demonstrated that Scu rescued HT22 cells from cytotoxicity induced by oxygen and glucose deprivation/reoxygenation (OGD/R). Scu also showed antioxidant activity by promoting nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, upregulating heme oxygenase-1 (HO-1) expression, increasing superoxide dismutase (SOD) activity, and inhibiting reactive oxygen species (ROS) generation in vitro. Additionally, Scu reduced nuclear factor-kappa B (NF-κB) activity and the levels of pro-inflammatory factors. Interestingly, these effects were abolished by Nrf2 inhibition. Furthermore, Scu reduced infarct volume and blood-brain barrier (BBB) permeability, improved sensorimotor functions and depressive behaviors, and alleviated oxidative stress and neuroinflammation in rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Mechanistically, Scu-induced Nrf2 nuclear accumulation and inactivation of NF-κB were accompanied by an enhanced level of phosphorylated protein kinase B (p-AKT) both in vitro and in vivo. Pharmacologically inhibiting the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway blocked Scu-induced Nrf2 nuclear translocation and inactivation of NF-κB, as well as its antioxidant and anti-inflammatory activities. In summary, these results suggest that Scu exhibits antioxidant, anti-inflammatory, and neuroprotective effects in CIRI through Nrf2 activation mediated by the PI3K/Akt pathway.
Topics: Humans; Animals; Rats; Proto-Oncogene Proteins c-akt; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; NF-kappa B; Antioxidants; Neuroinflammatory Diseases; Neuroprotective Agents; Oxidative Stress; Reperfusion Injury; Signal Transduction; Brain Ischemia
PubMed: 37611841
DOI: 10.1016/j.ejphar.2023.175979 -
Frontiers in Endocrinology 2023Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative... (Meta-Analysis)
Meta-Analysis
Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.
BACKGROUND
Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue.
MATERIALS AND METHOD
An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293).
RESULTS
The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected.
CONCLUSION
In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.
Topics: Humans; Male; Animals; Rats; Mice; Melatonin; Antioxidants; Iodine Radioisotopes; Semen; Thyroid Neoplasms; Oxidative Stress; Body Weight
PubMed: 37701901
DOI: 10.3389/fendo.2023.1184745