scholarly journals Effect of Telmisartan in the Oxidative Stress Components Induced by Ischemia Reperfusion in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Simón Quetzalcoatl Rodríguez-Lara ◽  
Walter Angel Trujillo-Rangel ◽  
Araceli Castillo-Romero ◽  
Sylvia Elena Totsuka-Sutto ◽  
Teresa Arcelia Garcia-Cobián ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gastrocnemius Muscle ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Angiotensin Ii Receptor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Oxidative Markers ◽  
Stress Components

The therapeutic effects of telmisartan, an angiotensin II receptor antagonist and a peroxisome proliferator-activated receptor-γ(PPAR-γ) agonist, have been demonstrated in several disorders. It has antioxidant and immune response modulator properties and has shown promising results in the treatment of an ischemia/reperfusion (I/R) lesion. In this study, a skeletal muscle (right gastrocnemius muscle) I/R lesion was induced in rats and different reperfusion times (1 h, 24 h, 72 h, 7-day, and 14-day subgroups) were assessed. Furthermore, levels of oxidative markers such as enzymatic scavengers (catalase (CAT) and superoxide dismutase (SOD)) and metabolites (nitrates and 8-oxo-deoxyguanosine) were determined. The degree of tissue injury (total lesioned fibers and inflammatory cell count) was also evaluated. We observed an increase in CAT and SOD expression levels under telmisartan treatment, with a decrease in injury and oxidative biomarker levels in the 72 h, 7-day, and 14-day subgroups. Telmisartan reduced oxidative stress and decreased the damage of the I/R lesion.

scholarly journals Differential Roles of Peroxisome Proliferator-Activated Receptor-αand Receptor-γon Renal Crystal Formation in Hyperoxaluric Rodents

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kazumi Taguchi ◽  
Atsushi Okada ◽  
Shuzo Hamamoto ◽  
Rei Unno ◽  
Takahiro Kobayashi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Injury ◽  
Crystal Formation ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tubular Cells ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) and related inflammatory and oxidative molecule expression were investigated in a hyperoxaluric rodent model to evaluate thein vivoefficacy of PPAR agonists in preventing renal crystal formation. PPAR expression was examined in a mouse hyperoxaluria kidney stone model induced by daily intra-abdominal glyoxylate injection. Therapeutic effects of the PPARαagonist fenofibrate and PPARγagonist pioglitazone were also assessed in a 1% ethylene glycol-induced rat model of hyperoxaluria. Crystal formation, inflammation, cell injury, apoptosis, and oxidative stress were compared to those of vehicle-treated controls. Quantitative reverse transcription-polymerase chain reaction revealed that PPARαand PPARγexpression decrease and increase, respectively, during crystal formation in hyperoxaluric kidneys. In addition, PPARαlocalized to the cytoplasm of both proximal and distal tubular cells, whereas PPARγaccumulated in the nucleus of proximal tubular cells. Furthermore, renal crystal formation was significantly less prevalent in pioglitazone-treated rats but higher in the fenofibrate-treated and fenofibrate/pioglitazone-cotreated groups compared to controls, thus indicating that pioglitazone, but not fenofibrate, markedly decreased cell inflammation, oxidative stress, and apoptosis. Collectively, the results demonstrated that PPARγsuppressed renal crystal formation via its antioxidative and anti-inflammatory effects; however, the renotoxicity of PPARαmay elicit the opposite effect.

scholarly journals Mitochondrial Dysfunction in Skeletal Muscle of a Fibromyalgia Model: The Potential Benefits of Melatonin

2019 ◽  
Vol 20 (3) ◽  
pp. 765 ◽  
Author(s):  
Gaia Favero ◽  
Francesca Bonomini ◽  
Caterina Franco ◽  
Rita Rezzani
Keyword(s):  
Oxidative Stress ◽  
Chronic Pain ◽  
Mitochondrial Dysfunction ◽  
Gastrocnemius Muscle ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Homeostasis ◽  
Potential Benefits ◽  
Pain Symptoms ◽  
And Oxidative Stress

Fibromyalgia syndrome (FMS) is considered a musculoskeletal disorder associated to other symptoms including chronic pain. Since the hypothesis of FMS etiogenesis is consistent with mitochondrial dysfunction and oxidative stress, we evaluated the pathophysiological correlation among these factors studying some proteins involved in the mitochondrial homeostasis. We focused our attention on the roles of peroxisome proliferator activated receptor gamma coactivator-1alpha (PGC-1α), mitofusin2 (Mfn2), and coenzyme Q10 (CoQ10) in reserpine-induced myalgic (RIM) rats that manifest fibromyalgia-like chronic pain symptoms. First, we underlined that RIM rats are a good model for studying the pathophysiology of FMS and moreover, we found that PGC-1α, Mfn2, and CoQ10 are involved in FMS. In fact, their expressions were reduced in gastrocnemius muscle determining an incorrect mitochondrial homeostasis. Today, none of the currently available drugs are fully effective against the symptoms of this disease and they, often, induce several adverse events; hence, many scientists have taken on the challenge of searching for non-pharmacological treatments. Another goal of this study was therefore the evaluation of the potential benefits of melatonin, an endogenous indoleamine having several functions including its potent capacity to induce antioxidant enzymes and to determine the protective or reparative mechanisms in the cells. We observed that melatonin supplementation significantly preserved all the studied parameters, counteracting oxidative stress in RIM rats and confirming that this indoleamine should be taken in consideration for improving health and/or counteract mitochondrial related diseases.

scholarly journals Renal Ischemia/Reperfusion Early Induces Myostatin and PCSK9 Expression in Rat Kidneys and HK-2 Cells

2021 ◽  
Vol 22 (18) ◽  
pp. 9884
Author(s):  
Chiara Barisione ◽  
Daniela Verzola ◽  
Silvano Garibaldi ◽  
Pier Francesco Ferrari ◽  
Giacomo Garibotto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Peroxisome Proliferator ◽  
Vascular Protection ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tubular Necrosis ◽  
Main Driver ◽  
Markers Of Oxidative Stress ◽  
Species Production

During visceral interventions, the transient clampage of supraceliac aorta causes ischemia/reperfusion (I/R) in kidneys, sometime resulting in acute renal failure; preclinical studies identified redox imbalance as the main driver of I/R injury. However, in humans, the metabolic/inflammatory responses seem to prevail on oxidative stress. We investigated myostatin (Mstn) and proprotein convertase subtilisin/kexin type 9 (PCSK9), proatherogenic mediators, during renal I/R. Compared to sham-operated animals, the kidneys of rats who had experienced ischemia (30 min) had higher Mstn and PCSK9 expression after 4 h of reperfusion. After 24 h, they displayed tubular necrosis, increased nitrotyrosine positivity, and nuclear peroxisome proliferator-activated receptor gamma coactivator-1alpha relocation, markers of oxidative stress and mitochondria imbalance. Mstn immunopositivity was increased in tubuli, while PCSK9 immunosignal was depleted; systemically, PCSK9 was higher in plasma from I/R rats. In HK-2 cells, both ischemia and reperfusion enhanced reactive oxygen species production and mitochondrial dysfunction. H2O2 upregulated Mstn and PCSK9 mRNA after 1 and 3.5 h, respectively. Accordingly, ischemia early induced Mstn and PCSK9 mRNA; during reperfusion Mstn was augmented and PCSK9 decreased. Mstn treatment early increased PCSK9 expression (within 8 h), to diminish over time; finally, Mstn silencing restrained ischemia-induced PCSK9. Our study demonstrates that renal I/R enhances Mstn and PCSK9 expression and that Mstn induces PCSK9, suggesting them as therapeutic targets for vascular protection during visceral surgery.

Natural Aldose Reductase Inhibitor: A Potential Therapeutic Agent for Non-alcoholic Fatty Liver Disease

2020 ◽  
Vol 21 (6) ◽  
pp. 599-609 ◽  
Author(s):  
Longxin Qiu ◽  
Chang Guo
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Aldose Reductase ◽  
Fatty Liver Disease ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver

Aldose reductase (AR) has been reported to be involved in the development of nonalcoholic fatty liver disease (NAFLD). Hepatic AR is induced under hyperglycemia condition and converts excess glucose to lipogenic fructose, which contributes in part to the accumulation of fat in the liver cells of diabetes rodents. In addition, the hyperglycemia-induced AR or nutrition-induced AR causes suppression of the transcriptional activity of peroxisome proliferator-activated receptor (PPAR) α and reduced lipolysis in the liver, which also contribute to the development of NAFLD. Moreover, AR induction in non-alcoholic steatohepatitis (NASH) may aggravate oxidative stress and the expression of inflammatory cytokines in the liver. Here, we summarize the knowledge on AR inhibitors of plant origin and review the effect of some plant-derived AR inhibitors on NAFLD/NASH in rodents. Natural AR inhibitors may improve NAFLD at least in part through attenuating oxidative stress and inflammatory cytokine expression. Some of the natural AR inhibitors have been reported to attenuate hepatic steatosis through the regulation of PPARα-mediated fatty acid oxidation. In this review, we propose that the natural AR inhibitors are potential therapeutic agents for NAFLD.

scholarly journals Shenmai Injection Exerts Neuroprotective Functions by Down-regulating MicroRNA-19a in H 2 O 2 -induced PC12 Cells

2022 ◽  
Author(s):  
Jing Wu ◽  
zhonghao li ◽  
xiaoke dong ◽  
siyuan yuan ◽  
jinmin liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Pc12 Cells ◽  
Ischemia Reperfusion ◽  
Reperfusion Therapy ◽  
Pathological Process ◽  
Cell Viability Assay ◽  
Shenmai Injection ◽  
Oxidative Markers ◽  
Viability Assay

Abstract Background: Acute ischemic stroke (AIS) and following reperfusion therapy-induced cerebral ischemia reperfusion (I/R) injury have been recognized as an important subject of cerebrovascular disease with high mortality. Oxidative stress is an important pathological process of cerebral I/R injury. microRNA-19a (miR-19a) is involved in I/R. As the organ protectant agent, Shenmai Injection (SMI) is widely used in the clinical treatment of cerebral infarction. Purpose: This study aims to explore whether SMI can reduce oxidative stress by regulating miR-19a, thereby treating I/R injury. Methods: The oxidative stress state of PC12 cells was induced by H2O2, and then the cells were cultured with SMI. The therapeutic effect of SMI was evaluated by detecting cellular superoxide dismutase (SOD), malondialdehyde (MDA) and other oxidative markers with the kit. Western blot, PCR, immunofluorescence and other techniques were used to elucidate the potential mechanism of SMI. Results: Cell viability assay results showed that SMI could improve the viability of PC12 cells stimulated by H2O2. Compared with the H2O2 group, after SMI treatment, the contents of MDA and reactive oxygen species (ROS) were significantly reduced, while the activity of SOD was significantly increased, and SMI could reduce apoptosis by increasing the content of adenosine 5'-triphosphate (ATP) in cells and enhancing the mitochondrial membrane potential (∆Ψm). Western blot and qRT-PCR results showed that these effects were partially achieved through the AMPK/Sirt1/PGC-1α pathway. The level of miR-19a was significantly increased in H2O2 group, and SMI could protect the cells by reducing miR-19a. Further investigated the target of miR-19a, and transfected cells with miR-19a mimic and inhibitor respectively. We found that AdipoR2 was a direct target of miR-19a, and miR-19a could inhibit AdipoR2/PI3K/Akt/mTOR pathway. Conclusion:SMI can activate AMPK/Sirt1/PGC-1α and AdipoR2/PI3K/Akt/mTOR pathways by reducing miR-19a levels, and protect PC12 cells stimulated by H2O2.

scholarly journals Telomeres and Telomerase in The Aging Heart

2017 ◽  
Vol 9 (3) ◽  
pp. 129
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Stem Cell ◽  
Heart Function ◽  
Heart Diseases ◽  
Diastolic Heart Failure ◽  
Peroxisome Proliferator ◽  
Telomere Shortening ◽  
Peroxisome Proliferator Activated Receptor ◽  
Aging Heart

BACKGROUND: Aging per se is a risk factor for reduced cardiac function and heart diseases, even when adjusted for aging-associated cardiovascular risk factors. Accordingly, aging-related biochemical and cell-biological changes lead to pathophysiological conditions, especially reduced heart function and heart disease.CONTENT: Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1a and PGC-1b in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging.SUMMARY: The aging myocardium with telomere shortening and accumulation of senescent cells restricts the tissue regenerative ability, which contributes to systolic or diastolic heart failure. Moreover, patients with ion-channel defects might have genetic imbalance caused by oxidative stress-related accelerated telomere shortening, which may subsequently cause sudden cardiac death. Telomere length can serve as a marker for the biological status of previous cell divisions and DNA damage with inflammation and oxidative stress. It can be integrated into current risk prediction and stratification models for cardiovascular diseases and can be used in precise personalized treatments.KEYWORDS: aging, telomere, telomerase, aging heart, mitochondria, cardiac stem cell

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