AT<Subscript><Emphasis Type="Italic">1</Emphasis></Subscript> Receptor Blockade Prevents Cardiac Dysfunction after Myocardial Infarction in Rats

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.     

Effects of H<Subscript>2</Subscript>O<Subscript>2</Subscript> on Microfilaments of Cultured Endothelial Cells

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.     

Thromboxane A<Subscript>2</Subscript> Inhibition

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.     

The role of PGE<Subscript>2</Subscript> in human atherosclerotic plaque on platelet EP<Subscript>3</Subscript> and EP<Subscript>4</Subscript> receptor activation and platelet function in whole blood

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.     

Anthracycline-induced phospholipase A<Subscript>2</Subscript> inhibition

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.     

Serotonin mediates PGE<Subscript>2</Subscript> overexpression through 5-HT<Subscript>2A</Subscript> and 5-HT<Subscript>3</Subscript> receptor subtypes in serum-free tissue culture of macrophage-like synovial cells

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.     

Effects of balneotherapy on serum IL-1, PGE<Subscript>2 </Subscript>and LTB<Subscript>4</Subscript> levels in fibromyalgia patients

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.     

Taxifolin prevents β-amyloid-induced impairments of synaptic formation and deficits of memory via the inhibition of cytosolic phospholipase A<Subscript>2</Subscript>/prostaglandin E<Subscript>2</Subscript> content

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.     

Molecular basis of the A<Subscript>2</Subscript>B in Taiwan

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.     

Lp-PLA<Subscript>2</Subscript> as a Marker of Cardiovascular Diseases

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.     

Recent Developments with Lipoprotein-Associated Phospholipase A<Subscript>2</Subscript> Inhibitors

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.     

CO<Subscript>2</Subscript> embolism can complicate transanal total mesorectal excision

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.

     

The effect of cessation of 2nd generation P<Subscript>2</Subscript>Y<Subscript>12</Subscript> inhibitor therapy on platelet reactivity in patients 1 year after acute myocardial infarction

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.     

Lp-PLA<Subscript>2</Subscript>: A New Target for Statin Therapy

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.     

Downregulation of CX<Subscript>3</Subscript>CR1 ameliorates experimental colitis: evidence for CX<Subscript>3</Subscript>CL1-CX<Subscript>3</Subscript>CR1-mediated immune cell recruitment

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.

     

State of the art of new P2Y<Subscript>12</Subscript> antagonists

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.     

Insulin-like growth factor I (IGF-1) supplementation prevents diabetesinduced alterations in coenzymes Q<Subscript>9</Subscript> and Q<Subscript>10</Subscript>

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