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Advanced Science (Weinheim,... Sep 2023Mitochondrial function impairment due to abnormal opening of the mitochondrial permeability transition pore (MPTP) is considered the central event in acute pancreatitis;...
Mitochondrial function impairment due to abnormal opening of the mitochondrial permeability transition pore (MPTP) is considered the central event in acute pancreatitis; however, therapeutic choices for this condition remain controversial. Mesenchymal stem cells (MSCs) are a family member of stem cells with immunomodulatory and anti-inflammatory capabilities that can mitigate damage in experimental pancreatitis. Here, it is shown that MSCs deliver hypoxia-treated functional mitochondria to damaged pancreatic acinar cells (PACs) via extracellular vesicles (EVs), which reverse the metabolic function of PACs, maintain ATP supply, and exhibit an excellent injury-inhibiting effect. Mechanistically, hypoxia inhibits superoxide accumulation in the mitochondria of MSCs and upregulates the membrane potential, which is internalized into PACs via EVs, thus, remodeling the metabolic state. In addition, cargocytes constructed via stem cell denucleation as mitochondrial vectors are shown to exert similar therapeutic effects to MSCs. These findings reveal an important mechanism underlying the role of mitochondria in MSC therapy and offer the possibility of applying mitochondrial therapy to patients with severe acute pancreatitis.
Topics: Acinar Cells; Acute Disease; Adenosine Triphosphate; Bile Acids and Salts; Cell Hypoxia; Cellular Reprogramming; Extracellular Vesicles; Membrane Potential, Mitochondrial; Mesenchymal Stem Cells; Mitochondria; Mitochondrial Permeability Transition Pore; Pancreas; Pancreatitis; Paracrine Communication; Superoxides; Umbilical Cord; Humans
PubMed: 37409821
DOI: 10.1002/advs.202207691 -
Biomedicine & Pharmacotherapy =... Sep 2023Cardiac hypertrophy is frequently associated with ventricular dysfunction and heart failure. Paeoniflorin, has been widely used to treat cardiovascular...
Cardiac hypertrophy is frequently associated with ventricular dysfunction and heart failure. Paeoniflorin, has been widely used to treat cardiovascular dysfunction-related diseases. However, the underlying mechanism has been unclear. Here, we investigated the potential inhibitory effects and mechanism of paeoniflorin on oxidative stress of cardiac hypertrophy induced by angiotensin II (AngII) in vitro. Using MTS assay, qRT-PCR, WGA staining assay, and western blot, different dosages (50-400 μM) of paeoniflorin were utilized to examine the antihypertrophy effects on H9c2 cells. Western blot examination revealed the presence of apoptosis-related proteins Bax, Bcl2, and Cytc, antioxidative stress-related proteins Nrf2, HO-1, SOD, and CAT, and mitophagy-related proteins PINK1 and Parkin. qRT-PCR was used to detect the mRNA expression of Bax, Bcl2, Nrf2, and HO-1. TUNEL, caspase3/9 enzyme viability, and MDA, T-AOC, and superoxide levels were all evaluated using commercial kits.The fluorescent probes DCFH-DA and JC-1 were employed to measure cellular ROS and MMP levels. Nrf2 siRNA was utilized to investigate Nrf2's role in paeoniflorin-treated cardiac hypertrophy. Paeoniflorin dramatically reduced cell section area (CSA) and hypertrophic marker (ANP, BNP) expression while inhibiting oxidative stress by modulating ROS and MDA, CAT, SOD, and T-AOC levels. Furthermore, in AngII-induced cardiomyocyte hypertrophy, paeoniflorin restores H9c2 apoptosis by restoring Bax, Bcl-2 Cyt-C, Caspase 3, and Caspase 9 levels. Paeoniflorin also restored Nrf2/HO-1 and PINK1/Parkin expression, and its anti-AngII activities were mediated by Nrf2, which was regulated by Nrf2 knockdown. In conclusion, Our data confirm that paeoniflorin alleviates cardiac hypertrophy through modulating oxidative stress and Nrf2 signaling pathway in vitro.
Topics: Animals; Rats; Angiotensin II; Apoptosis; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Cardiomegaly; Myocytes, Cardiac; NF-E2-Related Factor 2; Oxidative Stress; Protein Kinases; Proto-Oncogene Proteins c-bcl-2; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction; Superoxide Dismutase
PubMed: 37542855
DOI: 10.1016/j.biopha.2023.115253 -
Biomolecules Dec 2023Recent years have seen an increased interest in the role of oxidative stress (OS) in pregnancy. Pregnancy inherently heightens susceptibility to OS, a condition fueled... (Review)
Review
Recent years have seen an increased interest in the role of oxidative stress (OS) in pregnancy. Pregnancy inherently heightens susceptibility to OS, a condition fueled by a systemic inflammatory response that culminates in an elevated presence of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the circulatory system. The amplified OS in pregnancy can trigger a series of detrimental outcomes such as underdevelopment, abnormal placental function, and a host of pregnancy complications, including pre-eclampsia, embryonic resorption, recurrent pregnancy loss, fetal developmental anomalies, intrauterine growth restriction, and, in extreme instances, fetal death. The body's response to mitigate the uncontrolled increase in RNS/ROS levels requires trace elements that take part in non-enzymatic and enzymatic defense processes, namely, copper (Cu), zinc (Zn), manganese (Mn), and selenium (Se). Determination of ROS concentrations poses a challenge due to their short half-lives, prompting the use of marker proteins, including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and glutathione (GSH). These markers, indicative of oxidative stress intensity, can offer indirect assessments of pregnancy complications. Given the limitations of conducting experimental studies on pregnant women, animal models serve as valuable substitutes for in-depth research. This review of such models delves into the mechanism of OS in pregnancy and underscores the pivotal role of OS markers in their evaluation.
Topics: Animals; Female; Humans; Pregnancy; Antioxidants; Reactive Oxygen Species; Placenta; Oxidative Stress; Superoxide Dismutase; Catalase; Glutathione; Glutathione Peroxidase; Pregnancy Complications
PubMed: 38136639
DOI: 10.3390/biom13121768 -
Biomolecules Aug 2023Lipid peroxidation (LP) is the most important type of oxidative-radical damage in biological systems, owing to its interplay with ferroptosis and to its role in... (Review)
Review
Lipid peroxidation (LP) is the most important type of oxidative-radical damage in biological systems, owing to its interplay with ferroptosis and to its role in secondary damage to other biomolecules, such as proteins. The chemistry of LP and its biological consequences are reviewed with focus on the kinetics of the various processes, which helps understand the mechanisms and efficacy of antioxidant strategies. The main types of antioxidants are discussed in terms of structure-activity rationalization, with focus on mechanism and kinetics, as well as on their potential role in modulating ferroptosis. Phenols, pyri(mi)dinols, antioxidants based on heavy chalcogens (Se and Te), diarylamines, ascorbate and others are addressed, along with the latest unconventional antioxidant strategies based on the double-sided role of the superoxide/hydroperoxyl radical system.
Topics: Antioxidants; Lipid Peroxidation; Ascorbic Acid; Oxidative Stress; Ferroptosis; Superoxides
PubMed: 37759691
DOI: 10.3390/biom13091291 -
Antioxidants (Basel, Switzerland) Aug 2023Superoxide dismutase (SOD) is a class of enzymes that restrict the biological oxidant cluster enzyme system in the body, which can effectively respond to cellular... (Review)
Review
Superoxide dismutase (SOD) is a class of enzymes that restrict the biological oxidant cluster enzyme system in the body, which can effectively respond to cellular oxidative stress, lipid metabolism, inflammation, and oxidation. Published studies have shown that SOD enzymes (SODs) could maintain a dynamic balance between the production and scavenging of biological oxidants in the body and prevent the toxic effects of free radicals, and have been shown to be effective in anti-tumor, anti-radiation, and anti-aging studies. This research summarizes the types, biological functions, and regulatory mechanisms of SODs, as well as their applications in medicine, food production, and cosmetic production. SODs have proven to be a useful tool in fighting disease, and mimetics and conjugates that report SODs have been developed successively to improve the effectiveness of SODs. There are still obstacles to solving the membrane permeability of SODs and the persistence of enzyme action, which is still a hot spot and difficulty in mining the effect of SODs and promoting their application in the future.
PubMed: 37759978
DOI: 10.3390/antiox12091675 -
Free Radical Biology & Medicine Aug 2023Myocardial ischemia-reperfusion (IR) injury may result in cardiomyocyte dysfunction. Mitochondria play a critical role in cardiomyocyte recovery after IR injury. The...
Myocardial ischemia-reperfusion (IR) injury may result in cardiomyocyte dysfunction. Mitochondria play a critical role in cardiomyocyte recovery after IR injury. The mitochondrial uncoupling protein 3 (UCP3) has been proposed to reduce mitochondrial reactive oxygen species (ROS) production and to facilitate fatty acid oxidation. As both mechanisms might be protective following IR injury, we investigated functional, mitochondrial structural, and metabolic cardiac remodeling in wild-type mice and in mice lacking UCP3 (UCP3-KO) after IR. Results showed that infarct size in isolated perfused hearts subjected to IR ex vivo was larger in adult and old UCP3-KO mice than in equivalent wild-type mice, and was accompanied by higher levels of creatine kinase in the effluent and by more pronounced mitochondrial structural changes. The greater myocardial damage in UCP3-KO hearts was confirmed in vivo after coronary artery occlusion followed by reperfusion. S1QEL, a suppressor of superoxide generation from site I in complex I, limited infarct size in UCP3-KO hearts, pointing to exacerbated superoxide production as a possible cause of the damage. Metabolomics analysis of isolated perfused hearts confirmed the reported accumulation of succinate, xanthine and hypoxanthine during ischemia, and a shift to anaerobic glucose utilization, which all recovered upon reoxygenation. The metabolic response to ischemia and IR was similar in UCP3-KO and wild-type hearts, being lipid and energy metabolism the most affected pathways. Fatty acid oxidation and complex I (but not complex II) activity were equally impaired after IR. Overall, our results indicate that UCP3 deficiency promotes enhanced superoxide generation and mitochondrial structural changes that increase the vulnerability of the myocardium to IR injury.
Topics: Mice; Animals; Superoxides; Myocardial Ischemia; Myocytes, Cardiac; Mitochondria; Oxidative Stress; Myocardial Reperfusion Injury; Coronary Artery Disease; Energy Metabolism; Ischemia; Reperfusion; Fatty Acids; Infarction
PubMed: 37295539
DOI: 10.1016/j.freeradbiomed.2023.05.014 -
Revista Da Associacao Medica Brasileira... 2023The objective of this study was to investigate the protectiveness of resveratrol on cisplatin-induced damage to the ovary using experimental models.
OBJECTIVE
The objective of this study was to investigate the protectiveness of resveratrol on cisplatin-induced damage to the ovary using experimental models.
METHODS
A total of 30 female Wistar-Albino rats constituted the research material. The rats were categorized into three groups: Group 1 was administered one milliliter of 0.9% NaCl solution, Group 2 was administered 7.5 mg/kg cisplatin, and Group 3 was administered 7.5 mg/kg cisplatin and 10 mg/kg resveratrol. Ovaries were extirpated in all groups and subjected to biochemical and histopathological tests. Cisplatin-induced damage to ovarian tissue was graded and scored as the total histopathological findings score. The ovarian function was assessed using immunohistochemical staining for c-kit expression. Rats' malondialdehyde, catalase, and superoxide dismutase levels were determined.
RESULTS
The histopathological finding score was significantly higher in Group 2 than in other groups (p<0.05). The superoxide dismutase and catalase levels were significantly higher in Group 3 than in Group 2 (p<0.001 for both cases). The malondialdehyde level was significantly higher in Group 2 than in Group 3 (p<0.001).
CONCLUSION
The study findings demonstrated that resveratrol reduced ovarian injury and enhanced biochemical parameters following cisplatin-induced ovary damage in experimental models.
Topics: Rats; Female; Animals; Resveratrol; Ovary; Catalase; Cisplatin; Antioxidants; Rats, Wistar; Superoxide Dismutase; Malondialdehyde; Oxidative Stress
PubMed: 37585992
DOI: 10.1590/1806-9282.20230314 -
Neurobiology of Disease Aug 2023In patients with amyotrophic lateral sclerosis (ALS), disease symptoms and pathology typically spread in a predictable spatiotemporal pattern beginning at a focal site... (Review)
Review
In patients with amyotrophic lateral sclerosis (ALS), disease symptoms and pathology typically spread in a predictable spatiotemporal pattern beginning at a focal site of onset and progressing along defined neuroanatomical tracts. Like other neurodegenerative diseases, ALS is characterized by the presence of protein aggregates in postmortem patient tissue. Cytoplasmic, ubiquitin-positive aggregates of TDP-43 are observed in approximately 97% of sporadic and familial ALS patients, while SOD1 inclusions are likely specific to cases of SOD1-ALS. Additionally, the most common subtype of familial ALS, caused by a hexanucleotide repeat expansion in the first intron of the C9orf72 gene (C9-ALS), is further characterized by the presence of aggregated dipeptide repeat proteins (DPRs). As we will describe, cell-to-cell propagation of these pathological proteins tightly correlates with the contiguous spread of disease. While TDP-43 and SOD1 are capable of seeding protein misfolding and aggregation in a prion-like manner, C9orf72 DPRs appear to induce (and transmit) a 'disease state' more generally. Multiple mechanisms of intercellular transport have been described for all of these proteins, including anterograde and retrograde axonal transport, extracellular vesicle secretion, and macropinocytosis. In addition to neuron-to-neuron transmission, transmission of pathological proteins occurs between neurons and glia. Given that the spread of ALS disease pathology corresponds with the spread of symptoms in patients, the various mechanisms by which ALS-associated protein aggregates propagate through the central nervous system should be closely examined.
Topics: Humans; Amyotrophic Lateral Sclerosis; Superoxide Dismutase-1; Protein Aggregates; C9orf72 Protein; DNA-Binding Proteins
PubMed: 37394036
DOI: 10.1016/j.nbd.2023.106218