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AT<Subscript><Emphasis Type="Italic">1</Emphasis></Subscript> Receptor Blockade Prevents Cardiac Dysfunction after Myocardial Infarction in Rats 总被引:5,自引:0,他引:5
Berthonneche C Sulpice T Tanguy S O'Connor S Herbert JM Janiak P de Leiris J Boucher F 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2005,19(4):251-259
Summary Myocardial infarction (MI) can induce severe alterations of contractile function that can, in turn, lead to heart failure.
In a previous study, we have demonstrated that TNF-α was involved in cardiac contractile dysfunction 7 days after coronary
artery ligation in rats. Since Angiotensin II type 1 (AT1) receptor can be involved in TNF-α production, we have investigated whether early short-term treatment with irbesartan, an
AT1 receptor blocker, is able to limit TNF-α production within the heart and to improve cardiac function and geometry following
MI in rats.
Male Wistar rats were subjected to permanent coronary artery ligation and received either a placebo or irbesartan (50 mg/kg/day)
per os daily from day 3 to day 6 after surgery. On day 7, cardiac TNF-α was significantly reduced in MI rats receiving irbesartan
(p < 0.05). Moreover, irbesartan improved residual LV end-diastolic pressure under both basal conditions and after volume overload
(p < 0.01). In addition, a significant leftward shift of the pressure-volume curve in the irbesartan-treated group was found
versus placebo. Finally, infarct expansion index was also significantly improved by irbesartan (p < 0.01). In conclusion, early, short-term AT1 receptor blockade limits post-infarct cardiac TNF-α production and diminishes myocardial alterations observed 7 days after
MI in the rat. 相似文献
3.
Peter Roth Joachim Seybold Friedrich-Wilhelm Hehrlein Norbert Suttorp 《The International journal of angiology》2003,12(1):62-67
Hydrogen peroxide (H2O2) is an important granulocyte derived mediator of endothelial cell injury. Alterations of the microfilaments system (especially of actin) in endothelial cells may be relevant for the pathogenesis of vascular leakage. In the study presented effects of H2O2 on actin monomers (G-actin) and filamentous actin (F-actin) were examined in cultured pulmonary artery endothelial cells. Phalloidin which blocks actin depolymerization by inhibiting actin monomer dissociation and C. Botulinum C2 toxin which ADP-ribosylates G-actin thereby inhibiting actin polymerization were used as tools for the study of H2O2–related actin alterations. Exposure of cells to 2 mM H2O2 resulted in a biphasic change of F-actin with an early decrease (15 min) and a subsequent doubling (120 min) paralleled by an inverse G-actin pattern. In endothelial cells with a 20% reduction of F-actin-brought about by preincubation with C2-toxin for 150 min- H2O2-related actin polymerization was unimpaired. In cells with completely dissolved F-actin (Bot. C2-toxin for 210 min) no actin polymerization occurred upon H2O2 application. Phalloidin blocked the early H2O2-induced F-actin decrease and slowed down late actin polymerization. Effects of H2O2 on endothelial actin were abolished in the presence of scavengers of oxygen metabolites (catalase) and by the poly (ADP) ribose-polymerase inhibitor aminobenzamid. The data presented are compatible with the concept that H2O2 stimulates actin turnover and actin nucleation which—in the long run—result in H2O2 related formation of new actin filaments. This process was blocked by oxygen metabolite scavengers and by inhibition of DNA strand break repair mechanisms. 相似文献
4.
Jean-Michel Dogné Xavier de Leval Patricia Benoit Jacques Delarge Bernard Masereel 《Treatments in respiratory medicine》2002,1(1):11-17
Bronchial asthma is a disease defined by reversible airway obstruction, bronchial hyperresponsiveness and inflammation. In addition to histamine and acetylcholine, recent studies have emphasized the role of arachidonic acid metabolites (leukotrienes, prostaglandins and thromboxane A2) in the pathogenesis of asthma. Among these mediators, thromboxane A2 (TXA2) has attracted attention as an important mediator in the pathophysiology of asthma because of its potent bronchoconstrictive activity. Thromboxane A2 is believed to be involved not only in late asthmatic responses but also in bronchial hyperresponsiveness, a typical feature of asthma.Strategies for inhibition of TXA2 include TXA2 receptor antagonism and thromboxane synthase inhibition. Results of double-blind, placebo-controlled clinical trials have proven the efficacies of the thromboxane receptor antagonist seratrodast and the thromboxane synthase inhibitor ozagrel in the treatment of patients with asthma. Seratrodast and ozagrel are available in Japan for the treatment of asthma. Ramatroban, another thromboxane receptor antagonist, is currently under phase III clinical evaluation in Europe and Japan for the treatment of asthma.The pharmacological profiles of the thromboxane modulators may be improved by combination with leukotriene D4 receptor antagonists. A multi-pathway inhibitory agent such as YM 158, which is a novel orally active dual antagonist for leukotriene D4 and thromboxane A2 receptors, may have potent therapeutic effects in the treatment of bronchial asthma. Large scale clinical trials are necessary to further define the role of thromboxane modulators in the treatment of patients with asthma. 相似文献
5.
Schober LJ Khandoga AL Dwivedi S Penz SM Maruyama T Brandl R Siess W 《Journal of thrombosis and thrombolysis》2011,32(2):158-166
Atherosclerosis has an important inflammatory component. Macrophages accumulating in atherosclerotic arteries produce prostaglandin
E2 (PGE2), a main inflammatory mediator. Platelets express inhibitory receptors (EP2, EP4) and a stimulatory receptor (EP3) for this prostanoid. Recently, it has been reported in ApoE−/− mice that PGE2 accumulating in inflammatory atherosclerotic lesions might contribute to atherothrombosis after plaque rupture by activating
platelet EP3, and EP3 blockade has been proposed to be a promising new approach in anti-thrombotic therapy. The aim of our investigation was to
study the role of PGE2 in human atherosclerotic plaques on human platelet function and thrombus formation. Plaque PGE2 might either activate or inhibit platelets depending on stimulation of either EP3 or EP4, respectively. We found that the two EP3-antagonists AE5-599 (300 nM) and AE3-240 (300 nM) specifically and completely inhibited the synergistic effect of the EP3-agonist sulprostone on U46619-induced platelet aggregation in blood. However, these two EP3-antagonists neither inhibited atherosclerotic plaque-induced platelet aggregation, GPIIb/IIIa exposure, dense and alpha granule
secretion in blood nor reduced plaque-induced platelet thrombus formation under arterial flow. The EP4-antagonist AE3-208 (1–3 μM) potentiated in combination with PGE2 (1 μM) ADP-induced aggregation, demonstrating that PGE2 enhances platelet aggregation when the inhibitory EP4-receptor is inactivated. However, plaque-induced platelet aggregation was not augmented after platelet pre-treatment with
AE3-208, indicating that plaque PGE2 does not stimulate the EP4-receptor. We found that PGE2 was present in plaques only at very low levels (15 pg PGE2/mg plaque). We conclude that PGE2 in human atherosclerotic lesions does not modulate (i.e. stimulate or inhibit) atherothrombosis in blood after plaque rupture. 相似文献
6.
The purpose of this essay is to overview our findings that membrane-associated calcium-independent phospholipase A2 is markedly inhibited by low, clinically relevant concentrations of anthracyclines. Our studies suggest that due to the essential
role of this enzyme in membrane homeostasis, its inhibition can be one of the early culprits leading to anthracycline-induced
cardiac dysfunction. The clinical importance and potential pharmaceutical use of this new phenomenon await further studies. 相似文献
7.
Seidel MF Fiebich BL Ulrich-Merzenich G Candelario-Jalil E Koch FW Vetter H 《Rheumatology international》2008,28(10):1017-1022
Serotonin antagonists show impressive analgesic efficacy in rheumatoid arthritis, osteoarthritis (OA) or fibromyalgia; however, this effect is not well understood. We examined the mechanism of serotonin-induced inflammation and its antagonists in OA. Serotonin receptor subtypes and COX-2 were analysed by RT-PCR from synovial tissue. Serum-free cultures were stimulated with 10 muM serotonin and/or the antagonists ketanserin (5-HT(2A)), tropisetron (5-HT(3)) and parecoxib (COX-2). Prostaglandin E(2) (PGE(2)), tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta) and leukotriene B4 (LTB4) were measured by an immunoassay in the supernatants. RT-PCR results showed mRNA for 5-HT(2A) and 5-HT(3) receptors, and COX-2. PGE(2) in the supernatants increased by 261.2% +/- 56.7 (mean +/- SEM; P = 0.007) in response to serotonin. TNF-alpha, IL-1beta and LTB4 levels did not change. Ketanserin, tropisetron and parecoxib suppressed PGE(2). The serotonin-induced PGE(2) overexpression appeared thus to be mediated by 5-HT(2A) and 5-HT(3) receptors. This activation might involve COX-2. The findings may explain the potent benefit of 5-HT(3) antagonists. 相似文献
8.
The purpose of this study was to investigate the clinical effects of balneotherapy in the treatment of Fibromyalgia Syndrome
(FMS) and to determine if balneotherapy influences serum levels of inflammation markers, IL-1, PGE2 and LTB4. 24 primary fibromyalgia female patients diagnosed according to American College of Rheumatology criteria were included to
the study. Their ages ranged between 33 and 55 years. FMS patients were randomly assigned in two groups as, group 1 (n = 12) and group 2 (n = 12). Group 1 received 20-min bathing, once in a day for five days per week. Patients participated in the study for 3 weeks
(total of 15 sessions) in Denizli. Group 2 did not receive balneotherapy. FMS patients were evaluated by tenderness measurements
(tender point count and algometry), Visual Analogue Scale, Beck’s Depression Index, Fibromyalgia Impact Questionnaire. Ten
healthy women recruited group three as the controls. Serum PGE2, LTB4 and IL1-α levels were measured in all three groups. The biochemical measurements and clinical assessments were performed
before and at the end of general period of therapy. Statistically significant alterations in algometric score, Visual Analogue
score, Beck’s Depression Index and PGE2 levels (P < 0.001), numbers of tender points (P < 0.01) and Fibromyalgia Impact Questionnaire score (P < 0.05) were found after the balneotherapy between group 1 and 2. Mean PGE2 level of FMS patients were higher compared to healthy control group (P < 0.0001) and decreased after the treatment period, only in group 1 (P < 0.05). As in the group 2 and 3, detectable IL-1 and LTB4 measurements were insufficient, statistical analysis was performed, only in group 1. After balneotherapy IL-1 and LTB4 significantly decreased in group 1 (P < 0.05). In conclusion, balneotherapy is an effective choice of treatment in patients with FMS relieving the clinical symptoms,
and possibly influencing the inflammatory mediators. 相似文献
9.
Yuanyuan Wang Qinwen Wang Xiaoming Bao Yanfei Ding Jieyi Shentu Wei Cui Xiaowei Chen Xiaofei Wei Shujun Xu 《Metabolic brain disease》2018,33(4):1069-1079
Taxifolin is a potent flavonoid with anti-inflammatory activity. Taxifolin has been reported to decrease the accumulation of β-amyloid (Aβ), and reduce Aβ-induced neurotoxicity. However, the detail molecular mechanism of taxifolin against Aβ-induced neurotoxicity is largely unknown. In this study, we revealed the protective effects and the underlying mechanisms of taxifolin on the impairments of cognitive function and synapse formation induced by soluble Aβ oligomers. Our results showed that taxifolin prevented neuronal cell death in a concentration-dependent manner. The recognition memory in novel object recognition tasks and the spatial memory in Morris water maze tests are significantly lower in the Alzheimer’s disease (AD) model mice induced by hippocampal injection of Aβ42. Taxifolin treatment prevented the recognitive and spatial memory deficits of the AD mice. 10 mg/kg taxifolin treatment also significantly prevented the decreased expression levels of PSD 95 induced by Aβ42. Live cell imaging study showed that 2 h pre-treatment of taxifolin prevented the decrease in the number of filopodium and spine induced by Aβ42 oligomers. Aβ42 oligomers significantly increased the production of cytosolic phospholipase A2 (cPLA2), a crucial enzyme of pro-inflammatory mediator, and prostaglandin E2 (PGE2), a neuroinflammatory molecule. Taxifolin significantly reduced the content of cPLA2 and PGE2 induced by Aβ42 both in the primary hippocampal neurons and hippocampal tissues. These results indicated that taxifolin might prevent Aβ42 oligomer-induced synapse and cognitive impairments through decreasing cPLA2 and PGE2. Our study provided novel insights into the cellular mechanisms for the protective effects of taxifolin on AD. 相似文献
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Chang CS Lin KT Chang JG Lin CW Hsieh LL Yeh CJ Liu TC 《International journal of hematology》2008,88(2):127-133
Molecular genotyping of the ABO alleles has been widely used in ABO subgroups analysis and has been able to solve the rare ABO blood grouping discrepancies. The genotypes of sixty-one A(2)B phenotype donors recruited from the middle and south of Taiwan were analyzed by means of molecular methods. The A(2)B phenotype was initially identified by serological test. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to screen the ABO alleles at nucleotides (nt) 261 and 703 based on the nt differences found in the ABO alleles. The subgroups of the A(2) allele were determined by the PCR-RFLP and direct sequencing methods. The discrepancies between the phenotype and genotype of the A(2)B were then studied by subcloning and nucleotide sequence analysis. Our results show that 55 of the 61 A(2)B donors (90%) are A205/B allele and two are A201/B allele. Four cases were heterozygotes of the cis-AB/O or B alleles. Two were cis-AB04/O allele, one was cis-AB01/O allele and the other was cis-AB02/B allele. In conclusion, most A(2)B genotypes belong to the A205/B allele in Taiwan. In this study, we report for the first time the presence of the A205, A201, and cis-AB02 alleles in Taiwan. 相似文献
11.
Inflammation lies at the base of endothelial dysfunction, eventually leading to plaque formation. The degree of inflammation
defines the “vulnerability” of plaque to rupture. Numerous strategies have been adopted to identify and eventually treat high-risk
vulnerable plaque. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has emerged as one such candidate marker of inflammation that may play a direct role in the formation of rupture-prone plaque.
Epidemiologic studies have clearly demonstrated the prognostic ability of increased Lp-PLA2 levels and their association with increased risk of future coronary and cerebrovascular events. Moreover, Lp-PLA2 might have similar predictive power for both incident coronary heart disease in initially healthy individuals as well as
for recurrent events in those with clinically manifest atherosclerosis. The latest evidence has also suggested its incremental
value for risk determination over the well-established traditional risk factors and biomarkers in patients with congestive
heart failure. These data support an integral role of Lp-PLA2 activity in lipid peroxidation and cardiovascular risk assessment. This review summarizes the current body of evidence supporting
the clinical utility of Lp-PLA2 and its future applications in cardiovascular medicine. 相似文献
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Ryan J. Chauffe Robert L. Wilensky Emile R. MohlerIII 《Current atherosclerosis reports》2010,12(1):43-47
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a calcium-independent phospholipase A2 enzyme secreted by leukocytes and associated with circulating low-density lipoprotein and macrophages in atherosclerotic
plaques. Until recently, the biological role of Lp-PLA2 in atherosclerosis was controversial, but now the preponderance of evidence demonstrates a proatherogenic role of this enzyme.
Lp-PLA2 generates two proinflammatory mediators, lysophosphatidylcholine and oxidized nonesterified fatty acids, which play a major
role in the development of atherosclerotic lesions and formation of a necrotic core, leading to more vulnerable plaques. These
findings have opened the door to a potential novel therapeutic target, selective inhibition of Lp-LPA2. Recently, both animal models and human studies have shown that selective inhibition of Lp-PLA2 reduces plasma Lp-PLA2 activity, plaque area, and necrotic core area. This article reviews the most recent developments with Lp-PLA2 inhibitors. 相似文献
13.
C. R. Harnsberger K. Alavi J. S. Davids P. R. Sturrock M. Zayaruzny J. A. Maykel 《Techniques in coloproctology》2018,22(11):881-885
Background
Carbon dioxide (CO2) embolism is a rare but potentially devastating complication of minimally invasive abdominal and retroperitoneal surgery. Characterized by a decrease in end-tidal CO2 (ETCO2) and oxygen saturation (SpO2), CO2 emboli can cause rapid intraoperative hypotension and cardiovascular collapse. Transanal total mesorectal excision (taTME) is a novel surgical approach for rectal resection, which requires high flow CO2 insufflation in a low volume operative field. In this setting, the incidence of CO2 embolism is unknown; we evaluate three cases of intraoperative CO2 embolism that occurred during the transanal portion of the TME dissection.Methods
All taTME cases from December 2014 to March 2018 at a single institution were reviewed. Cases of CO2 embolism were identified intraoperatively and characterized using the operative reports and anesthesia records. The transanal/pelvic insufflation included a targeted pressure of 15 mm Hg, high flow and high smoke evacuation. Physiologic derangements and management of these instances were analyzed. The postoperative course was evaluated and any complications were noted.Results
A total of 80 taTME were performed for benign and malignant disease. Three patients (4%) developed intraoperative evidence of CO2 embolism. Each instance occurred during the transanal portion of the dissection. Physiologic changes were marked by abrupt decrease in end-tidal ETCO2, SpO2, and blood pressure (BP). Management included immediate release of pneumopelvis, hemodynamic support with crystalloid or vasopressors, and placement of the patient in the Trendelenburg position with left side down. Within 10 min of the acute event, all patients had return of ETCO2, SpO2, and BP to pre-event levels. There were no intraoperative or postoperative sequelae including arrhythmia, myocardial infarction, stroke or death. No cases required conversion to open.Conclusions
During taTME, rare CO2 emboli may occur in the setting of venous bleeding during pneumopelvis, causing sudden, transient cardiovascular instability. Immediate recognition of rapid decrease in ETCO2, SpO2, and BP should be followed by desufflation of pneumopelvis, patient positioning in Trendelenburg and left lateral decubitus, and hemodynamic support. Increased awareness of this potential complication and maintaining a high index of suspicion will lead to preparedness of the anesthesia and surgery teams.14.
Guy Witberg Jalal Bathish Tamir Bental Dorit Leshem-Lev Abid Assali Ran Kornowski Eli Lev 《Journal of thrombosis and thrombolysis》2018,46(3):351-358
To assess the effect of cessation of dual antiplatelet therapy (DAPT) regimens containing 2nd generation P2Y12 inhibitors on platelet reactivity, in patients who completed 12 months of DAPT following an acute myocardial infarction. Clinical data has shown an increased cardiovascular risk in the 90 days following cessation of DAPT. One possible explanation is a transient platelet hyper-reactivity after cessation of treatment. Data from patients treated with 2nd generation P2Y12 inhibitors is scarce. Patients who completed 12 month DAPT with prasugrel/ticagrelor underwent serial assessment of platelet reactivity (on DAPT and 1, 4 and 12 weeks post cessation). The primary outcome was platelet reactivity, expressed as platelet reactivity units (PRU) at each time point. 41 participants were included in this study, (23 ticagrelor, 18 prasugrel). There was no statistically significant differences in baseline characteristics between prasugrel/ticagrelor treated patients . The pattern of platelet reactivity recovery after DAPT cessation differed between the ticagrelor and prasugrel: with ticagrelor, after the initial PRU increase from baseline, the PRU remained stable, while with prasugrel, there was a further increase in PRU between 1 and 4 weeks, with a return to the 1 week level by 12 weeks (p?=?0.034 for the time?×?treatment interaction between ticagrelor and prasugrel). Our results suggest there is a transient platelet hyper-reactivity after cessation of ADP receptor blockers therapy with prasugrel, but not ticagrelor. Further research is required to elucidate the pathophysiologic mechanisms behind these findings and to evaluate potential strategies to prevent or overcome this “rebound” effect. 相似文献
15.
Inflammation plays an important role in atherogenesis and plaque vulnerability. Inflammatory-type markers have been evaluated
for their association with atherosclerotic vascular disease and their ability to improve cardiovascular disease (CVD) risk
stratification. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vascular-specific inflammatory enzyme that increases the risk of CVD events and stroke approximately twofold. A consensus
panel recently recommended the measurement of Lp-PLA2 in moderate-risk and high-risk patients for improved risk stratification and modification of low-density lipoprotein target
levels. Lipid-lowering agents, particularly statins, lower Lp-PLA2 mass and activity; therefore, Lp-PLA2 may represent an important target of lipid-lowering therapy for reducing the inflammatory nature of atherosclerosis and plaque
vulnerability. It is unknown whether lowering inflammatory markers such as Lp-PLA2 will have a direct benefit on CVD events and mortality. A large morbidity and mortality trial was recently initiated to evaluate
the long-term safety and efficacy of darapladib, an Lp-PLA2 antagonist, in patients with high-risk coronary heart disease. 相似文献
16.
Felix?Becker Christina?Holthoff Christoph?Anthoni Emile?Rijcken J.?Steven?Alexander Felicity?N.?E.?Gavins HU?Spiegel Norbert?Senninger Thorsten?Vowinkel
Purpose
Inflammatory conditions like inflammatory bowel diseases (IBD) are characterized by increased immune cell infiltration. The chemokine ligand CX3CL1 and its receptor CX3CR1 have been shown to be involved in leukocyte adhesion, transendothelial recruitment, and chemotaxis. Therefore, the objective of this study was to describe CX3CL1-CX3CR1-mediated signaling in the induction of immune cell recruitment during experimental murine colitis.Methods
Acute colitis was induced by dextran sodium sulfate (DSS), and sepsis was induced by injection of lipopolysaccharide (LPS). Serum concentrations of CX3CR1 and CX3CL1 were measured by ELISA. Wild-type and CX3CR1-/- mice were challenged with DSS, and on day 6, intravital microscopy was performed to monitor colonic leukocyte and platelet recruitment. Intestinal inflammation was assessed by disease activity, histopathology, and neutrophil infiltration.Results
CX3CR1 was upregulated in DSS colitis and LPS-induced sepsis. CX3CR1-/- mice were protected from disease severity and intestinal injury in DSS colitis, and CX3CR1 deficiency resulted in reduced rolling of leukocytes and platelets.Conclusions
In the present study, we provide evidence for a crucial role of CX3CL1-CX3CR1 in experimental colitis, in particular for intestinal leukocyte recruitment during murine colitis. Our findings suggest that CX3CR1 blockade represents a potential therapeutic strategy for treatment of IBD.17.
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The interaction of ADP with its platelet receptor P2Y12 plays a crucial role in platelet activation and thrombogenesis. This
article reviews the pharmacology and clinical trials of specific antagonists of P2Y12. Clopidogrel is a thienopyridine with
proven antithrombotic efficacy, but it has some important drawbacks: (a) it is a pro-drug that needs to be metabolized to
its active metabolite; (b) it has a delayed onset and offset of action and (c) there is high inter-individual variability
in pharmacological response. Prasugrel is also a thienopyridine, with faster onset of action and a more uniform inhibition
of platelet function compared to clopidogrel, accounting for lower incidence of ischemic events in patients with acute coronary
syndromes (ACS) undergoing percutaneous coronary intervention (PCI) and higher incidence of both non-CABG-related bleeding
complications. Two direct and reversible P2Y12 antagonists, Cangrelor and ticagrelor, are characterized by rapid onset and
reversal of platelet inhibition. Cangrelor is not superior to clopidogrel in preventing thrombotic events in patients undergoing
PCI. Ticagrelor is superior to clopidogrel in preventing major adverse cardiac events in ACS patients, but, like prasugrel,
is associated with a higher frequency of non-CABG-related bleeding complications. A shorter period of drug discontinuation
before surgery is necessary in ticagrelor-treated patients compared to clopiodgrel-treated patients to limit the severity
of post-surgical bleeding. 相似文献
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Diabetes, which causes enhanced oxidative stress, is a multifactorial disease that leads to deleterious effects in many organ
systems within the body. Ubiquinones (coenzyme Q9 and Q10) are amphipathic molecular components of the electron transport chain that function also as endogenous antioxidants and attenuate
the diabetes-induced decreases in antioxidant defense mechanisms. Insulin-like growth factor 1 (IGF-1) is considered to be
an “essential surviving factor”, the level and function of which are compromised in diabetes. This study investigated the
impact of IGF-1 supplementation on ubiquinone levels in a rat model of type I diabetes. Adult male Sprague-Dawley rats were
divided into four groups: control, control plus IGF-1, diabetic and diabetic plus IGF-1. Diabetic animals received a single
intravenous injection of streptozotocin (STZ, 55 mg/kg). IGF-1 supplementation groups received a daily intraperitoneal dose
of 3 mg IGF-1 per kilogram body weight for 7 weeks. Coenzyme Q9 and Q10 levels were assessed by ultraviolet detection on high pressure liquid chromatography. STZ caused a significant reduction
in body weight and an elevation in blood glucose level, which were not prevented by IGF-1 supplementation. In addition Q9 and Q10 levels in diabetic liver were significantly elevated. IGF-1 supplementation prevented liver alterations in Q10 but not Q9 levels. Q9 and Q10 levels in diabetic kidney were significantly depressed, and these deleterious effects were abolished by IGF-1 treatment.
These data suggest that IGF-1 antagonizes the diabetes-induced alterations in endogenous antioxidants including coenzyme Q10, and hence may have a therapeutic role in diabetes.
Received: 28 March 2002 / Accepted in revised form: 5 December 2002
Correspondence to J. Ren 相似文献