Myofibrillar, mitochondrial and valvular morphological alterations in cardiac hypertrophy among copper-deficient rats

Histological aspects of Cu-deficient hypertrophied rat hearts were evaluated to determine causal factors. Twenty-four male weanling rats were fed either Cu-adequate (8.0 mg/kg diet) or Cu-deficient (0.4 mg/kg diet) diets until 9 or 11 wk of age. Copper-deficient rats had increased mitochondrial:myofibrillar ratios compared with Cu-adequate rats. Mitochondria were vacuolated. Cristae seemed fragmented and matrix seemed translucent and they tended to distort the myofibrils. Glycogen granules and lipid droplets were more frequently observed in Cu-deficient rats. When the Cu-deficient rats were examined separately, the larger hearts in the older rats had smaller mitochondrial:myofibrillar ratios, but had larger myofibrillar volume densities. Valves from Cu-deficient rats had less connective tissue and seemed fragmented in areas. In 9-wk-old Cu-deficient rats, there was a negative correlation between heart: body weight ratios and bicuspid valve scores, whereas 11-wk-old rats demonstrated the same relationship for tricuspid valves with myofibril volume density. These results suggest that there are two components contributing to cardiac hypertrophy in copper deficient rats: 1) an enlarged mitochondrial area and 2) myofibrillar enlargement. Hematocrit values did not seem to be related to cardiac hypertrophy.     

Systemic toxicity from subchronic dermal exposure, chemical characterization, and dermal penetration of catalytically cracked clarified slurry oil

Clarified slurry oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 male and 10 female Sprague-Dawley rats 5 days/week for 13 weeks at doses of 8, 30, 125, or 500 mg/kg/day, and to another group for 2 weeks at doses of 2000 mg/kg/day. The rats were fitted with cardboard Elizabethan collars to minimize the ingestion of the test material, which was applied undiluted and remained uncovered on the skin. A similar group of rats served as controls; they were treated in the same manner except that no CSO was applied to their skin. There was a dose-related mortality and depression of body weight gain in the rats treated with CSO at doses of 30 mg/kg/day or greater; none of the rats dosed at 2000 mg/kg/day survived more than 2 weeks. The primary target organs of CSO toxicity were the liver, thymus, and bone marrow. The effects on the liver included increased weight (250% at 500 mg/kg/day), cholangiolitis, diffuse liver cell degeneration and hypertrophy, necrosis, fibrosis, decreased serum glucose, increased levels of alkaline phosphatase, aspartate aminotransferase, alanine amino transferase, bilirubin, and triglycerides. The thymus was found to be small and upon microscopic examination to be atrophic or hypoplastic. Erythroid hypoplasia was found in the bone marrow of some of the rats dosed at 30 mg/kg/day and increased in severity with increasing dose. The erythroid hypoplasia was accompanied by a dose-related anemia. Even in the rats dosed at 8 mg/kg/day, very slight abnormalities in the bile ducts were observed upon microscopic examination of the liver. Chromatographic separation and analyses demonstrated that CSO contains about 58% 3- to 5-ring polycyclic aromatic hydrocarbons (PAHs) and approximately 8-10% carbazole derivatives. In vitro and in vivo skin penetration studies demonstrated that the carbazole materials penetrate through the skin to a considerable extent (about 44%); less penetration was observed with 2- or 3-ring (8-13%) or 5-ring PAHs (3%).     

Induction of hepatocellular carcinoma in nonhuman primates by the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline.

The heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was evaluated for carcinogenic effects in macaques, primarily cynomolgus monkeys. IQ was administered by gavage five times a week at doses of 10 or 20 mg/kg. IQ induced hepatocellular carcinoma in 55% of the animals at the low dose and in 95% of the animals at 20 mg/kg. The average latent period at the high dose level was 43 months and that at the low dose was 60 months. Generally, the tumor nodules exhibited a well- to moderately well-differentiated hepatocellular carcinoma, and a trabecular pattern was most frequently seen. Pulmonary metastases were also found in several of the monkeys. Thus, IQ is a potent carcinogen in nonhuman primates and is a potential carcinogen for humans.     

Preconditioning with Short-Term Dietary Restriction Attenuates Cardiac Oxidative Stress and Hypertrophy Induced by Chronic Pressure Overload

Left ventricular (LV) hypertrophy and associated heart failure are becoming a more prevalent and critical public health issue with the aging of society, and are exacerbated by reactive oxygen species (ROS). Dietary restriction (DR) markedly inhibits senescent changes; however, prolonged DR is difficult. We herein investigated whether preconditioning with short-term DR attenuates chronic pressure overload-induced cardiac hypertrophy and associated oxidative stress. Male c57BL6 mice were randomly divided into an ad libitum (AL) diet or 40% restricted diet (DR preconditioning, DRPC) group for 2 weeks prior to ascending aortic constriction (AAC), and all mice were fed ad libitum after AAC surgery. Two weeks after surgery, pressure overload by AAC increased LV wall thickness in association with LV diastolic dysfunction and promoted myocyte hypertrophy and cardiac fibrosis in the AL+AAC group. Oxidative stress in cardiac tissue and mitochondria also increased in the AL+AAC group in association with increments in cardiac NADPH oxidase-derived and mitochondrial ROS production. LV hypertrophy and associated cardiac dysfunction and oxidative stress were significantly attenuated in the DRPC+AAC group. Moreover, less severe mitochondrial oxidative damage in the DRPC+AAC group was associated with the suppression of mitochondrial permeability transition and cardiac apoptosis. These results indicate that chronic pressure overload-induced cardiac hypertrophy in association with cardiac and mitochondrial oxidative damage were attenuated by preconditioning with short-term DR.     

Reduced cardiac selenium content in the acquired immunodeficiency syndrome

Selenium deficiency has been implicated in the pathogenesis of a dilated congestive cardiomyopathy in areas of China (Keshan disease) and in several patients on long-term total parenteral nutrition. Recently a clinically and pathologically similar cardiomyopathy has been described in AIDS. Since blood selenium levels are low in AIDS, we assayed cardiac selenium status by a spectrofluorometric method in eight AIDS patients at autopsy compared to nine age-matched, non-AIDS autopsy controls with histologically normal hearts. We found (mean +/- SD) a cardiac selenium level of 0.327 +/- 0.082 microgram/g dry weight in AIDS vs 0.534 +/- 0.184 microgram/g dry weight in controls (p less than 0.01; Student's t test). There were no significant differences between the groups for heart weight, serum CPK, or other laboratory parameters. No specific chest x-ray or electrocardiographic abnormalities were present. Histologically, all AIDS hearts were abnormal; mostly with mild degrees of muscle hypertrophy or fibrosis. Foci of myocytolysis and myocyte necrosis and fibrous replacement of myocytes and monocytic infiltration were present in two AIDS cases. We conclude that heart tissue in AIDS demonstrates a significant selenium deficit. These data provide a potential link between selenium deficiency and cardiomyopathy in AIDS.     

Calcium reintroduction decreases viability of cardiac myocytes from copper-deficient rats.

Copper deficiency leads to profound cardiac hypertrophy and failure. Myocytes were isolated from hearts of copper-deficient and copper-adequate male Holtzman rats to characterize size and function of the cells. Weanling rats were offered a semipurified diet low in copper in two separate experiments (Experiment 1, 0.45 mg Cu/kg and Experiment 2, 0.30 mg Cu/kg). Control (copper-adequate) rats drank water supplemented with cupric sulfate (20 mg Cu/L). Compared with copper-adequate rats, copper-deficient rats had lower hematocrits, liver copper concentrations and plasma ceruloplasmin activities, and higher heart weights and liver iron concentrations. When myocytes were isolated in low calcium media (1 micromol/L), cell viability was not affected by diet history. However, upon restoration to more physiologic levels of calcium (1 mmol/L), cells from copper-deficient rats were less viable, exhibiting an average loss of 34 and 40% in Experiments 1 and 2, respectively, compared with a 9.5 and 13% loss of cells, respectively, from the copper-adequate rats. Addition of the calcium channel blocker, verapamil, did not block this calcium-dependent loss of viability nor did the mitochondrial calcium channel blockers, ruthenium red and cyclosporin A. For comparison with another model of cardiac hypertrophy, the calcium sensitivity of myocytes from hypertrophic hearts of Sprague-Dawley rats with aortic constrictions was found not to differ from that of sham-operated rats. Thus, cardiac hypertrophy associated with postnatal copper deficiency results in a unique increased calcium intolerance of isolated myocytes.     

Dietary fish oil preserves cardiac function in the hypertrophied rat heart

Regular fish or fish oil intake is associated with a low incidence of heart failure clinically, and fish oil-induced reduction in cardiac remodelling seen in hypertrophy models may contribute. We investigated whether improved cardiac energy efficiency in non-hypertrophied hearts translates into attenuation of cardiac dysfunction in hypertrophied hearts. Male Wistar rats (n 33) at 8 weeks of age were sham-operated or subjected to abdominal aortic stenosis to produce pressure-overload cardiac hypertrophy. Starting 3 weeks post-operatively to follow initiation of hypertrophy, rats were fed a diet containing 10 % olive oil (control) or 5 % fish oil (ROPUFA? 30 (17 % EPA, 10 % DHA))+5 % olive oil (FO diet). At 15 weeks post-operatively, ventricular haemodynamics and oxygen consumption were evaluated in the blood-perfused, isolated working heart. Resting and maximally stimulated cardiac output and external work were >60 % depressed in hypertrophied control hearts but this was prevented by FO feeding, without attenuating hypertrophy. Cardiac energy efficiency was lower in hypertrophy, but greater in FO hearts for any given cardiac mass. Coronary blood flow, restricted in hypertrophied control hearts, increased with increasing work in hypertrophied FO hearts, revealing a significant coronary vasodilator reserve. Pronounced cardiac dysfunction in hypertrophied hearts across low and high workloads, indicative of heart failure, was attenuated by FO feeding in association with membrane incorporation of n-3 PUFA, principally DHA. Dietary fish oil may offer a new approach to balancing the high oxygen demand and haemodynamic requirements of the failing hypertrophied heart independently of attenuating hypertrophy.     

RATES OF PROTEIN SYNTHESIS IN DIFFERENT REGIONS OF THE NORMOTENSIVE AND HYPERTROPHIED HEART IN RESPONSE TO ACUTE ALCOHOL TOXICITY

The objective of study was (a) to investigate whether proteinsynthesis in different regions of the heart (i.e. left and rightatria, left and right ventricles) expressed equal sensitivityto acute ethanol dosage, and (b) to ascertain whether concomitantcardiac abnormalities (i e. experimental hypertrophic heartdisease) exacerbated these responses. Acute ethanol dosage (75mmol/kg body weight. i.p.) to mature male Wistar rats reducedthe fractional rate of protein synthesis (k₅ %/day) in all regions(atria and ventricles) of the normal and overloaded (30 daysaortic constricted) hearts. The responses in k₃ were variable.In normal heart, the atrial tissues showed a slightly greaterdecrease in k₅ (approx. –30%) when compared to the ventricularregions (approx –2O%). The most pronounced effects occurredin the hypertrophied left ventricular tissues where the depressiveeffects of ethanol on the rate of protein synthesis were potentiatedin the presence of hypertrophy (k₃, reduced by approx 40%).Other regions of the overloaded heart did not show additionalsensitivity to the effects of ethanol on protein synthesis inthe presence of chronic hypertension. In conclusion, the deleteriouseffects of ethanol on the left ventricle are additive in thepresence of chronic hypertrophy. These results may have importantimplications for other cardiac abnormalities where there isalso concomitant ethanol exposure.     

Pathohistological changes in endomyocardial biopsy specimens in patients with myotonic dystrophy

BACKGROUND: Endomyocardial biopsies in patients with myotonic dystrophy (MD) have, so far, shown changes such as myofibrillar degeneration, mitochondrial abnormalities, focal myocarditis, fibrosis and fatty infiltration of the myocardium and the conduction system. METHODS: This study presents the results of endomyocardial biopsy in 10 patients with MD. Endomyocardial biopsy was carried out using King's bioptome. RESULTS: In two patients with servere MD biopsy specimens showed changes compatible with border line myocarditis. In five patients with moderate to severe forms of MD fibrosis and fatty infiltration of the myocardium were found in addition to degenerative changes and hypertrophy of muscle fibers. Three patients with mild MD had non-specific degenerative and hypertrophic myocardial changes. The histological changes described above were present in patients without cardiological symptoms and in those with normal ECG and echocardiographic findings. Only two of the 10 patients in whom endomyocardial biopsy was done complained of fatigue and occasional palpitations while the rest were asymptomatic. One patient with focal myocarditis had ECG signs of left bundle branch block and echocardiographic evidence of reduced left ventricular contractility. Five patients with signs of endomyocardial fibrosis only had an abnormal Q wave on ECG recordings. The remaining five patients with border line myocarditis i.e. with degenerative and hypertrophic myocardial changes had normal ECG and echocardiographic findings. CONCLUSIONS: These results stress the significance of endomyocardial biopsy in detecting myocardial pathologic changes in patients with MD.     

Regression of dietary copper restriction-induced cardiomyopathy by copper repletion in mice

Dietary copper deficiency (CuD)(3) leads to cardiac hypertrophy in various animal models. We showed recently that heart failure develops after hypertrophy in FVB mice fed a CuD diet. The present study was undertaken to determine whether CuD-induced cardiac failure is reversible upon copper repletion (CuR). Dams of FVB mice were fed a CuD diet (0.3 mg/kg) starting from d 3 postdelivery; the weanling pups were fed the same diet until CuR with 6.0 mg/kg Cu in the diet at 4 or 5 wk of age. CuR at 4 wk of age prevented the body weight loss; at 5 wk of age, it resulted in the regaining of the lost weight caused by CuD. A significant regression of CuD-induced cardiac hypertrophy was observed in the CuR mice. Histopathological examination revealed that CuR eliminated CuD-caused lipid deposition in the myocardium, and electron microscopy demonstrated that CuD-induced ultrastructural changes such as mitochondrial swelling and organelle structural disarray were all reversed in the CuR mice. Hemodynamic analysis showed that the CuD-depressed systolic and diastolic parameters such as the maximal rate of left ventricular pressure rise (+dP/dt) and decline (-dP/dt), and the contraction and relaxation times were completely recovered in the CuR mice. Furthermore, the CuD-blunted myocardial responses to the beta-adrenergic agonist, isoproterenol, were also restored in the CuR mice. This study thus demonstrates for the first time that CuR results in the regression of heart failure induced by CuD as demonstrated by the reversal of depressed cardiac hemodynamic and contractile function and the restored responsiveness to beta-adrenergic stimulation.     

Valsartan in the treatment of heart failure or left ventricular dysfunction after myocardial infarction

The physiological role of the renin angiotensin aldosterone system (RAAS) is to maintain the integrity of the cardiovascular system. The effect of angiotensin II is mediated via the angiotensin type I receptor (AT1 ) resulting in vasoconstriction, sodium retention and myocyte growth changes. This causes myocardial remodeling which eventually leads to left ventricular hypertrophy, dilation and dysfunction. Inhibition of the RAAS with angiotensin converting enzyme (ACE) inhibitors after acute myocardial infarction has been shown to reduce cardiovascular morbidity and mortality. Angiotensin receptor blockers (ARBs) specifically inhibit the AT1 receptor. It has not been known until the performance of the VALIANT (valsartan in acute myocardial infarction trial) whether blockade of the angiotensin receptor with an ARB or combination of an ACE inhibitor and ARB leads to similar outcomes as an ACE inhibitor. The VALIANT trial demonstrated equal efficacy and non-inferiority of the ARB valsartan 160 mg bid compared with captopril 50 mg tds, when administered to high risk patients with left ventricular dysfunction or heart failure in the immediate post myocardial infarction period. The combination therapy showed no incremental benefit over ACE inhibition or an ARB alone and resulted in increased adverse effects. This review examines the role of valsartan in left ventricular dysfunction post myocardial infarction. We also discuss pharmacokinetics, dosing, side effects, and usage in the elderly.     

Morphometric analysis of myocardium from copper-deficient pigs

Volume densities and ultrastructure of mitochondria and myofibrils from hearts of copper-deficient pigs were evaluated in two studies. Weaned male pigs (21 d of age) were fed purified diets with adequate copper (Study 1: 7.1 mg Cu/Kg, n=4; Study 2: 8.4 mg Cu/Kg, n=6) or no copper added (Study 1:1.2 mg Cu/kg, n=4; Study 2: 0.84 mg Cu/Kg, n=5). Pigs in both studies fed the copper-deficient diet developed symptoms of copper deficiency, including decreased levels of the micronutrient in liver, heart and plasma, and increased heart to body weight ratio. Morphometric evaluation revealed a significant increase in mitochondrial volume density and in the ratio of mitochondria to myofibril volume densities in copper-deficient hearts. The myofibril volume density and the heart to body weight ratio was positively correlated in study 1, suggesting that the enlarged hearts of the Cu deficient pigs were due to an increase in the volumes of both mitochondria and myofibril compartments. Mitochondria in areas appeared vacuolated and cristae were fragmented in the copper-deficient pig myocardium as opposed to the normal parallel array of these structures. Separated myofilaments and deposits of glycogen granules were also evident in the copper-deficient pig heart. These results suggest that copper-deficiency alters the ultrastructural characteristics of the pig heart in a similar manner as previously reported for the laboratory rat.     

辛伐他汀对阿霉素致心衰兔心功能的影响

目的：探讨不同剂量辛伐他汀对阿霉素所致心衰兔保护作用及其抗心衰的机制。方法：雄性新西兰大耳白兔60只,随机数字表法分为正常对照组（CON）、CHF模型组（CHF）、CHF＋辛伐他汀低剂量组（LD-SIM）、CHF＋辛伐他汀中剂量组（MD-SIM）、CHF＋辛伐他汀高剂量组（HD-SIM）。正常对照组（CON）给予耳缘静脉等体积生理盐水,每周1次,共10周。其余组均给予生理盐水注射液稀释的盐酸阿霉素,按4 mg/kg,每周1次,共10次,而辛伐他汀干预组同时给予低、中、高剂量辛伐他汀灌胃治疗,剂量分别为0.3 mg/（kg·d）,1.5 mg/（kg·d）,3.0 mg/（kg·d）。10周后测定大鼠心功能左室肥厚指数、ELISA测定血清中hs-CRP和MMP-13含量。结果：各药物治疗组可不同程度改善左室肥厚,其中辛伐他汀大剂量组与CHF模型组比较差异有统计学意义（P〈0.01）,而辛伐他汀中剂量组与其比较差异有统计学意义（P〈0.05）,而小剂量治疗组与之比较差异无统计学意义（P〉0.05）;大中剂量治疗组心功能指标（＆#177;dp/dtmax）明显优于模型组,差异有统计学意义（P〈0.01）,辛伐他汀大剂量组与中剂量组比较差异无统计学意义（P〉0.05）,而小剂量治疗组与模型组比较差异无统计学意义（P〉0.05）;各药物治疗组能降低血清中CRP、MMP-13含量（P〈0.01或P〈0.05）。结论：辛伐他汀能够预防左心肥厚,降低血浆CRP、MMP-13浓度,从而减缓细胞外基质（ECM）的降解改善心功能,这可能是辛伐他汀抗心衰作用机制之一。     

腺病毒siRNA沉默 Raf-1基因抑制异丙肾上腺素 诱导大鼠心肌肥厚

摘要:目的　研究Raf-1 siRNA重组腺病毒载体对大鼠心肌肥厚的作用并探讨其机制。方法　构建Raf-1腺病毒siRNA 载体,大鼠随机分为正常对照组、心肌肥厚组、无关siRNA 组、Raf-1 siRNA 干预组,皮下注射异丙肾上腺素（ISO）制备大鼠心肌肥厚模型,无关siRNA 组及Raf-1 siRNA 干预组注射ISO后,分别经心包腔注射重组腺病毒pAd-siCon及pAd-siRaf-1,4周后染色测定全心重指数（HWI）、心肌细胞横截面积（CSA）、心肌间质胶原容积分数（CVF）及血管周围胶原面积（PVCA）,western blot检测心肌Raf-1、NF-κB及ERK1/2蛋白表达,RT- PCR检测TNF-α、MCP-1、TGF-β1 mRNA表达。结果　与心肌肥厚组相比,Raf-1 siRNA 干预组可降低大鼠HWI、CSA、CVF及PVCA,下调Raf-1、NF-κB、ERK1/2蛋白及TNF-α、MCP-1、TGF-β1 mRNA表达;无关siRNA 组与心肌肥厚组相比无明显差异。结论　Raf-1 siRNA重组腺病毒载体能减轻大鼠心肌肥厚,其作用可能与抑制Raf-1/ NF-κB、Raf-1/ ERK1/2信号转导及下调肿瘤坏死因子-α（TNF-α）、单核细胞趋化蛋白-1（MCP-1）、转化生长因子-β（TGF-β）表达相关。     

Disposition of 2,6-di-tert-butyl-4-nitrophenol (DBNP), a submarine atmosphere contaminant, in male Sprague-Dawley rats

The phenol 2,6-di-tert-butyl-4-nitrophenol (DBNP) is a contaminant found onboard submarines and is formed by the nitration of an antioxidant present in turbine lubricating oil TEP 2190. DBNP has been found on submarine interior surfaces, on eating utensils and dishes, and on the skin of submariners. DBNP exposure is a potential health concern because it is an uncoupler of mitochondrial oxidative phosphorylation. Adult male rats were dosed once by oral gavage with 15 or 40 mg/kg DBNP mixed with 14C-DBNP in kanola oil and 0.8% v/v DMSO (n = 16/group). The distribution of 14C in major tissues was measured over time for up to 240 h post-dose. Unexpectedly, 6/16 (40%) of the rats gavaged with 40 mg/kg DBNP died within 24 h of dosing. Prostration, no auditory startle response, reduced locomotor activity, and muscular rigidity persisted in survivors for up to 8 days after dosing. For animals dosed with 15 mg/kg DBNP, radioactivity levels were significantly elevated in the following tissues 24h after dosing: fat>liver>kidneys>heart>lungs>brain>striated muscle>spleen. Radioactivity levels were elevated for fat, liver, kidney, heart, and lungs of animals euthanized 144 h post-dosing and in the liver of animals euthanized 240 h post-dosing. These findings suggest that DBNP may accumulate in the body as a result of continuous or repeat exposures of short interval to DBNP.     

Survival,growth, and histopathological effects of paraquat ingestion in nestling american kestrels(Falco sparverius)

The use of paraquat as a herbicide is becoming more extensive with the increasing popularity of no tillage agriculture, increasing the possibility of exposure for wildlife species. American kestrel(Falco sparverius) nestlings were orally dosed daily with 5 l/g of distilled water (controls), 10 mg/kg, 25 mg/kg, or 60 mg/kg of paraquat dichloride (1,1-dimethyl-4,4-bipyridinium) in distilled water from day 1 through day 10. Forty-four percent of the nestlings given 60 mg/kg died after 4 days. Significant differences in growth rates occurred between controls and all paraquat-dosed groups. Reduced skeletal growth occurred in the humerus and femur in the 25 mg/kg and 60 mg/kg groups, and in the radius-ulna and tibiotarsus in the 60 mg/kg group. Skeletons were otherwise normal in appearance. Histopathological examination revealed localized focal necrosis in the liver of one nestling in the 60 mg/kg group and tubular cell degeneration and focal tubular dilation in the kidneys of another. The brain and lungs were unremarkable histologically. These findings suggest that altricial nestling kestrels are more sensitive to paraquat exposure than young or adult birds of precocial species.     

Conditioned nutritional requirements and the pathogenesis and treatment of myocardial failure

The majority of symptomatic patients with congestive heart failure have been shown to be significantly malnourished. Myocardial and skeletal muscle energy reserves are also diminished. Total daily energy expenditure in these patients is less than that in control individuals, and high protein-calorie feeds do not reverse the abnormalities; thus, the wasting that occurs in patients with congestive heart failure is metabolic rather than because of negative protein-calorie balance. Several specific deficiencies have been found in the failing myocardium: a reduction in the content of L-carnitine, coenzyme Q10, creatine and thiamine, nutrient cofactors that are important for myocardial energy production; a relative deficiency of taurine, an amino acid that is integral to the modulation of intracellular calcium levels; and an increase in myocardial oxidative stress, and a reduction of both endogenous and exogenous antioxidant defences. In addition, these processes may influence skeletal muscle metabolism and function. Cellular nutritional requirements conditioned by metabolic abnormalities in heart failure are important considerations in the pathogenesis of the skeletal and cardiac muscle dysfunction. A comprehensive restoration of adequate myocyte nutrition would seem to be essential to any therapeutic strategy designed to benefit patients suffering from this disease.     

Protection of myocardium in streptozotocin-induced diabetic rats by water extracts of Hsian-tsao (Mesona procumbens Hemsl.)

The myocardial protective effects of water extracts from Hsian-tsao (Mesona procumbens Hemsl.) on diabetic rats were investigated. Thirty Sprague-Dawley male rats were randomly divided into three groups, "control group" (n=10) with intraperitoneal saline injection, "diabetic group" (n=10) with 60 mg of intraperitoneal streptozotocin injection per kg of body weight and "Hsian-tsao group" (n=10) with intragastric administration of Hsian-tsao extracts every day for 4 weeks after intraperitoneal streptozotocin injection. Body weight and blood sugar concentrations were measured before and after model induction in the three groups. Thrombospondin-1 (TSP-1) expressions in the myocardium were monitored by immunohistochemistry and rt-RT-qPCR analysis. Myocardial ultrastructural changes were also analyzed by us-ing transmission electron microscopy. Our results demonstrated that diabetic myocardial ultrastructural changes included myofibrillar disarrangements, mitochondria disruption, and an increase in nuclear membrane invaginations. These damages were significantly less severe in the Hsian-tsao group compared with the diabetic group. A significant increase of the TSP-1 expression was also observed in the hearts of the diabetic rats (p<0.01), but it was relatively lower in the Hsian-tsao group than in the diabetic group (p<0.01). It suggested that Hsian-tsao treatment in the diabetic rats effectively prevented the pathological alterations in the myocardium and decreased TSP-1 expression.