Journal of physiology and biochemistry
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J. Physiol. Biochem. · Feb 2020
Rosuvastatin protects isolated hearts against ischemia-reperfusion injury: role of Akt-GSK-3β, metabolic environment, and mitochondrial permeability transition pore.
The cardioprotective activity of rosuvastatin (R) is yet to be known. The objective of this study was to research whether R perfusion before global ischemia can mitigate myocardial ischemia-reperfusion damage, considering the metabolic condition in which these effects occur, and to contemplate potential mitochondrial benefits. Protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) and mitochondrial permeability transition pore (MPTP) are key elements in myocardial injury produced by ischemia-reperfusion. ⋯ MPTP opening was delayed to 300 μM CaCl2, while use of W resulted in MPTP opening at 200 μM CaCl2. Electron microscopy showed better mitochondrial preservation with R, which reduced lactic acid production, increased glycogen consumption and G6PDH activity, as well as phosphorylation of Akt and GSK-3β. R before ischemia is cardioprotective against ischemic and reperfusion damage, activating Akt and regulating GSK-3β negatively and attenuating the MPTP opening.
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J. Physiol. Biochem. · Feb 2019
Hepatoprotective effect of gastrodin against alcohol-induced liver injury in mice.
Alcoholic liver disease (ALD) is a common and serious threat to human health worldwide. In this study, the hepatoprotective effect of gastrodin against alcohol-induced liver injury in mice was examined. Mice with alcohol-induced hepatotoxicity were treated intragastrically with gastrodin (50, 80, or 100 mg/kg). ⋯ Gastrodin protected against alcohol-induced increases in expression levels of the cytochrome P450 2E1 (CYP2E1) and mRNA levels of chemokine (C-X-C motif) ligand 1 (CXCL-1), interferon-γ (IFN-γ), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), vascular cell adhesion molecule 1 (VCAM-1), nuclear factor-kappa B (NF-κB), Toll-like receptor 4 (TLR-4), and activator of transcription 3 (STAT-3). Moreover, gastrodin-increased nuclear transcription factor 2 (Nrf2) translocates to the nucleus and enhanced the activity of anti-oxidant enzymes, and could thereby ameliorate alcohol-induced liver injury in mice. This study demonstrated that gastrodin may be an effective therapeutic agent against alcohol-induced liver injury.
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J. Physiol. Biochem. · May 2017
Comparative StudyContribution of inducible and neuronal nitric oxide synthases to mitochondrial damage and melatonin rescue in LPS-treated mice.
NOS isoform activation is related to liver failure during sepsis, but the mechanisms driving mitochondrial impairment remain unclear. We induced sepsis by LPS administration to inducible nitric oxide synthase (iNOS-/-) and neuronal nitric oxide synthase (nNOS-/-) mice and their respective wild-type controls to examine the contribution of iNOS to mitochondrial failure in the absence of nNOS. To achieve this goal, the determination of messenger RNA (mRNA) expression and protein content of iNOS in cytosol and mitochondria, the mitochondrial respiratory complex content, and the levels of nitrosative and oxidative stress (by measuring 3-nitrotyrosine residues and carbonyl groups, respectively) were examined in the liver of control and septic mice. ⋯ Moreover, the nNOS gene did not modify the expression and the effects of iNOS here shown. Melatonin administration counteracted iNOS activation and mitochondrial damage and enhanced the expression of the respiratory complexes above the control values. These effects were unrelated to the presence or absence of nNOS. iNOS is a main target to prevent liver mitochondrial impairment during sepsis, and melatonin represents an efficient antagonist of these iNOS-dependent effects whereas it may boost mitochondrial respiration to enhance liver survival.
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J. Physiol. Biochem. · Feb 2017
Comparative StudyChronic type-I diabetes could not impede the anti-inflammatory and anti-apoptotic effects of combined postconditioning with ischemia and cyclosporine A in myocardial reperfusion injury.
It has been shown that diabetes modifies the myocardial responses to ischemia/reperfusion (I/R) and to cardioprotective agents. In this study, we aimed to investigate the effects of combined treatment with ischemic postconditioning (IPostC) and cyclosporine A (CsA) on inflammation and apoptosis of the diabetic myocardium injured by I/R. Eight weeks after induction of diabetes in Wistar rats, hearts were mounted on a Langendorff apparatus and were subsequently subjected to a 30-min regional ischemia followed by 45-min reperfusion. ⋯ However, in diabetic animals, after administration of CsA, the cardioprotective effects of IPostC in increasing the p-GSK3β and Bcl-2 and decreasing apoptosis and inflammation were restored in comparison with nonpostconditioned diabetic hearts. IPostC or CsA failed to affect apoptosis and inflammation and failed to protect the diabetic myocardium against I/R injury. However, combined administration of IPostC and CsA at reperfusion can protect the diabetic myocardium by decreasing the inflammatory response and apoptosis.
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J. Physiol. Biochem. · Mar 2016
Effect of estrogen and/or progesterone administration on traumatic brain injury-caused brain edema: the changes of aquaporin-4 and interleukin-6.
The role of aquaporin-4 (AQP4) and interleukin-6 (IL-6) in the development of brain edema post-traumatic brain injury (TBI) has been indicated. The present study was designed to investigate the effect(s) of administration of progesterone (P) and/or estrogen (E) on brain water content, AQP4 expression, and IL-6 levels post-TBI. The ovariectomized rats were divided into 11 groups: sham, one vehicle, two vehicles, E1, E2, P1, P2, E1 + P1, E1 + P2, E2 + P1, and E2 + P2. ⋯ Our findings suggest that estrogen or progesterone by itself has more effective roles in decrease of brain edema than combination of both. Possible mechanism may be mediated by the alteration of AQP4 and IL-6 expression. However, further studies are required to verify the exact mechanism.