scholarly journals Combined Therapy with SS31 and Mitochondria Mitigates Myocardial Ischemia-Reperfusion Injury in Rats

2018 ◽  
Vol 19 (9) ◽  
pp. 2782 ◽  
Author(s):  
Fan-Yen Lee ◽  
Pei-Lin Shao ◽  
Christopher Wallace ◽  
Sarah Chua ◽  
Pei-Hsun Sung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Adult Male ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Left Ventricular Ejection ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Myocardial Ischemia Reperfusion ◽  
Sirt3 Expression

Myocardial ischemia-reperfusion (IR) injury contributes to adverse cardiac outcomes after myocardial ischemia, cardiac surgery, or circulatory arrest. In this study, we evaluated the ability of combined SS31-mitochondria (Mito) therapy to protect heart cells from myocardial IR injury. Adult male SD rats (n = 8/each group) were randomized: group 1 (sham-operated control), group 2 (IR, 30-min ischemia/72 h reperfusion), group 3 (IR-SS31 (2 mg intra-peritoneal injection at 30 min/24 h/48 h after IR)), group 4 (IR-mitochondria (2 mg/derived from donor liver/intra-venous administration/30 min after IR procedure)), and group 5 (IR-SS31-mitochondria). In H9C2 cells, SS31 suppressed menadione-induced oxidative-stress markers (NOX-1, NOX-2, oxidized protein) while it increased SIRT1/SIRT3 expression and ATP levels. In adult male rats 72 h after IR, left ventricular ejection fraction (LVEF) was highest in sham-operated control animals and lowest in the IR group. LVEF was also higher in IR rats treated with SS31-Mito than untreated IR rats or those treated with Mito or SS31 alone. Areas of fibrosis/collagen-deposition showed the opposite pattern. Likewise, levels of oxidative-stress markers (NOX-1, NOX-2, oxidized protein), inflammatory markers (MMP-9, CD11, IL-1β, TNF-α), apoptotic markers (mitochondrial-Bax, cleaved-caspase-3, PARP), fibrosis markers (p-Smad3, TGF-β), DNA-damage (γ-H2AX), sarcomere-length, and pressure/volume overload markers (BNP, β-MHC) all showed a pattern opposite that of LVEF. Conversely, anti-apoptotic (BMP-2, Smad1/5) and energy integrity (PGC-1α/mitochondrial cytochrome-C) markers exhibited a pattern identical to that of LVEF. This study demonstrates that the combined SS31-Mito therapy is superior to either therapy alone for protecting myocardium from IR injury and indicates that the responsible mechanisms involved increased SIRT1/SIRT3 expression, which suppresses inflammation and oxidative stress and protects mitochondrial integrity.

Neohesperidin alleviated pathological damage and immunological imbalance in rat myocardial ischemia-reperfusion injury via inactivation of JNK and NF-κB p65

2021 ◽  
Vol 85 (2) ◽  
pp. 251-261
Author(s):  
Aihua Li ◽  
Xin Zhang ◽  
Qiuping Luo
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Inflammatory Cytokines ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Oxidative Stress Markers ◽  
Antitumor Effects ◽  
Stress Markers ◽  
Myocardial Ischemia Reperfusion

ABSTRACT Neohesperidin (NEO) exerts antiviral, antioxidant, anti-inflammation, and antitumor effects in some diseases. The purpose of this study was to investigate the effect and mechanism of NEO on myocardial ischemia-reperfusion (I/R) injury. Results indicated that NEO suppressed the levels of serum inflammatory cytokines, myocardial damage markers, and oxidative stress markers, and increased the levels of antioxidant in myocardial I/R rats. NEO also inhibited cell apoptosis. Besides, NEO also inhibited the phosphorylation of c-Jun N-terminal kinases (JNK) and nuclear factor kappa B (NF-κB) p65. Furthermore, the protective effects of NEO on myocardial tissue damage, inflammatory cytokines, myocardial injury markers, oxidative stress markers, cell apoptosis, spleen, thymus and liver indices, and phagocytic indices were reversed by JNK activator and NF-κB activator, respectively. In conclusion, NEO alleviates myocardial damage, oxidative stress, cell apoptosis, and immunological imbalance in I/R injury via the inactivation of JNK and NF-κB, making NEO a potential agent for myocardial I/R therapy.

scholarly journals Oxidative stress burden inhibits spermatogenesis in adult male rats: testosterone protective effect

2018 ◽  
Vol 96 (4) ◽  
pp. 372-381 ◽  
Author(s):  
Samy Makary ◽  
Mohamed Abdo ◽  
Ereny Fekry
Keyword(s):  
Oxidative Stress ◽  
Aromatase Inhibitor ◽  
Adult Male ◽  
Male Rats ◽  
Testicular Toxicity ◽  
Oxidative Stress Markers ◽  
Sperm Viability ◽  
Protective Agents ◽  
Stress Markers ◽  
Anti Inflammatory

In this study, we aimed to investigate the protective effects of androgens, using letrozole (LET; an aromatase inhibitor), grape seed extract (GSE; a naturally occurring aromatase inhibitor and antioxidant), and testosterone propionate (Tp), against methotrexate (MTX)-induced testicular toxicity in adult male rats. MTX has been shown to induce oxidative stress and exhibit antiproliferative effects in the testes. Adult male rats received oral saline gavage (control group with no treatment), the potential protective agents (LET, GSE, or Tp) alone, MTX alone, or a combination of one of the potential protective agents and MTX. The testicular levels of oxidative stress markers and cytokines (tumor necrosis factor-α and interleukin-1β) were measured. Spermatogenesis and sperm viability were microscopically evaluated. Administration of LET and GSE 7 days before MTX improved spermatogenesis and sperm viability, as well as reduced the levels of oxidative stress markers and cellular cytokines. Exogenous testosterone exhibited anti-inflammatory and antioxidant activities, similar to GSE and LET. We also showed that enhancing the endogenous androgenic activity by LET and GSE protected spermatogenesis against MTX-induced testicular toxicity via reduction of inflammation and oxidative stress in the testes. Our data suggest that testosterone protected spermatogenesis owing to its antioxidant and anti-inflammatory properties.

scholarly journals microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Li ◽  
Hongbo Zhang ◽  
Zhanhu Li ◽  
Xiaoju Yan ◽  
Yuan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Mouse Models ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Gene Assay ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. Methods MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. Results Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. Conclusion Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.

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