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[This corrects the article DOI: 10.3389/fimmu.2022.1028733.].
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Mitochondria play a central role in cellular energy metabolism, and their dysfunction is increasingly recognized as a critical factor in the pathogenesis of diabetes-related cardiac pathophysiology, including vulnerability to ischemic events that culminate in myocardial infarction on the one hand and ventricular arrhythmias on the other. In diabetes, hyperglycemia and altered metabolic substrates lead to excessive production of reactive oxygen species (ROS) by mitochondria, initiating a cascade of oxidative stress that damages mitochondrial DNA, proteins, and lipids. This mitochondrial injury compromises the efficiency of oxidative phosphorylation, leading to impaired ATP production. The resulting energy deficit and oxidative damage contribute to functional abnormalities in cardiac cells, placing the heart at an increased risk of electromechanical dysfunction and irreversible cell death in response to ischemic insults. While cardiac mitochondria are often considered to be relatively autonomous entities in their capacity to produce energy and ROS, their highly dynamic nature within an elaborate network of closely-coupled organelles that occupies 30-40% of the cardiomyocyte volume is fundamental to their ability to exert intricate regulation over global cardiac function. In this article, we review evidence linking the dynamic properties of the mitochondrial network to overall cardiac function and its response to injury. We then highlight select studies linking mitochondrial ultrastructural alterations driven by changes in mitochondrial fission, fusion and mitophagy in promoting cardiac ischemic injury to the diabetic heart.
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Cardiomiopatias Diabéticas , Metabolismo Energético , Mitocôndrias Cardíacas , Isquemia Miocárdica , Estresse Oxidativo , Humanos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Animais , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/etiologia , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Isquemia Miocárdica/patologia , Dinâmica Mitocondrial , Mitofagia , Espécies Reativas de Oxigênio/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Transdução de SinaisRESUMO
Aging, a complex physiological process affecting all living things, is a major area of research, particularly focused on interventions to slow its progression. This study assessed the antiaging efficacy of dapagliflozin (DAPA) on various aging-related parameters in a mouse model artificially induced to age. Forty male Swiss albino mice were randomly divided into four groups of ten animals each. The control group (Group I) received normal saline. The aging model group (Group II) was administered D-galactose orally at 500mg/kg to induce aging. Following the aging induction, the positive control group received Vitamin C supplementation (Group III), while the DAPA group (Group IV) was treated with dapagliflozin. The inflammatory mediators (TNF-α and IL-1ß) showed similar patterns of change. No statistically significant difference was observed between groups III and IV. Both groups had significantly lower values compared to GII, while it was significantly higher compared to GI. Glutathione peroxidase (GSH-Px) showed no statistically significant difference between groups GIII and GIV, but it was higher in GIII compared to GII and significantly lower in GIII compared to GI. The study demonstrated that dapagliflozin exerts a beneficial impact on many indicators of aging in mice. The intervention resulted in a reduction in hypertrophy in cardiomyocytes, an enhancement in skin vitality, a decrease in the presence of inflammatory mediators, and an improvement in the efficacy of antioxidants.
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Envelhecimento , Compostos Benzidrílicos , Glucosídeos , Inflamação , Estresse Oxidativo , Animais , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/uso terapêutico , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Masculino , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Biomarcadores/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-1beta/metabolismoRESUMO
<b>Background and Objective:</b> Lead poisoning (Pb) is a big problem because it is found in almost all objects in daily life such as vehicle fuel, water pipes, ceramics, cosmetics and others. Continuous lead exposure can increase ROS resulting in an increase in hepatic IL-6 and caspase 3 which replaces hepatic cell apoptosis. The objective of this study was to determine the effect of <i>Apium graveolens</i> (celery) extract on plasma IL-6 and hepatic caspase 3 levels. <b>Materials and Methods:</b> This study used a post-test control group design. The research subjects were 20 Wistar rats that met the inclusion criteria and were divided into 4 groups randomly, namely (a) Sham group that had no treatment, (b) Negative control group was induced with lead acetate 200 mg kg<sup>1</sup> body weight/day without any treatment (c) Positive control group and (d) Treated group. On the 15th day, blood was taken to check IL-6 levels and tissue was taken for liver caspase 3 examination by immunohistochemical method. Data analysis used the one-way ANOVA test and continued with the <i>post hoc</i> LSD test. <b>Results:</b> The highest mean caspase 3 expression was in the control group 45.84±4.39 pg mL<sup>1</sup>, while the mean of IL-6 plasma level was highest in the P1 641.33±39.72 pg mL<sup>1</sup> group. The Mann-Whitney test showed a significant difference in IL-6 levels between the study groups (p = 0.000). The Mann-Whitney test showed a significant difference in caspase 3 levels between the study groups (p = 0.000). <b>Conclusion:</b> Giving celery extract 300 mg kg<sup>1</sup> body weight/day affects plasma IL-6 and hepatic caspase 3 levels in lead acetate-induced rats.
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Apium , Intoxicação por Chumbo , Compostos Organometálicos , Animais , Ratos , Apium/química , Peso Corporal , Caspase 3/efeitos dos fármacos , Interleucina-6/sangue , Interleucina-6/química , Interleucina-6/metabolismo , Intoxicação por Chumbo/tratamento farmacológico , Fígado/metabolismo , Modelos Animais , Extratos Vegetais/farmacologia , Ratos Wistar , Verduras/químicaRESUMO
Most human malignancies are attributed to exposure to infectious organisms such as viruses. Certain infections that can induce cancer can evade the immune system, leading to persistent inflammation that facilitates uncontrolled cell growth. Moreover, these pathogens can increase the likelihood of oncogenic transformation, leading to cancer development. Despite significant advancements in medicine, oncological research continues to seek innovative treatment techniques in light of the constraints imposed by traditional therapeutic agents. Virus-based therapy is a novel treatment method that has garnered significant interest due to its broad range of applications. Virotherapy employs oncolytic viruses that are genetically modified to target tumor cells specifically, undergo replication inside them and destroy the malignant cells. Additionally, this therapeutic approach elicits an anticancer response by boosting the patient's immune system. In addition, viruses are commonly employed as targeted delivery vectors for the precise transportation of various genes, medicinal compounds and immune-stimulating substances. Furthermore, virotherapy offers more excellent anticancer activity in combination with established treatment modalities such as immune therapy, chemotherapy and radiation therapy. This review presents a concise overview of the roles played by infectious agents, such as viruses in cancer progression. In addition, we have thoroughly summarized the advancements in utilizing viruses for their oncolytic properties in conjunction with established cancer treatment modalities such as chemotherapy, radiation and immunotherapy.
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Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Terapia Viral Oncolítica/métodos , Neoplasias/terapia , Neoplasias/patologia , Imunoterapia/métodosRESUMO
[This corrects the article DOI: 10.3389/fphar.2023.1096614.].
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OBJECTIVE: Treatment with cyclosporine(CsA) for a long-term period may induce renal glomerulosclersosis and interstitial fibrosis. Reactive oxygen species(ROS) seems to be involved in the process of glomerulosclersosis and interstitial fibrosis. We investigated the effect of CsA on the generation of ROS and extracellular matrix accumulation in cultured human mesangial cells. We also studied the relationship between ROS formation and extracellular matrix and the effect of antioxidant on ROS formation and/or extracellular matrix degradation. METHODS: Mesangial cells were treated with varying dose of Cyclosporine(0, 2.5, 5, 7.5 and 10microgram/ mL) and also with cyclosporine(5microgram/mL) plus N- acetylcysteine(1mM). ROS was measured by flow cytometric analysis. mRNA expression of MMP-2, TIMP-2, MT1-MMP and collagen III was assessed by RT-PCR method. MMP-2 activity was measured by gelatin zymography. RESULTS: No significant difference was noted in cell viability with each CsA concentration. CsA inhibited the cell proliferation in a dose dependent manner and induced the expression of ROS. Antioxidant NAC reversed the effect of cyclosporine. CsA had no effect on the mRNA expression of collagen III, MMP-2, TIMP-2, MT1-MMP. However CsA decreased the MMP-2 activity in a dose dependent manner, which was also reversed by NAC. CONCLUSION: Cyclosporine-induced ROS may be associated with the extracellular matrix accumulation, that is glomerulosclersosis and interstitial fibrosis by inhibiting the cell proliferation and by decreasing the degradation of extracellular matrix. Antioxidant, at least in vitro, may prevent some of the adverse effects of CsA on renal function.