Protective effect of Ginkgo biloba against experimental cardiotoxicity induced by isoproterenol in adult male albino rats a histological and biochemical study

The present study was designed to investigate whether Ginkgo biloba [GB] might protect the heart against myocardial injury induced by isoproterenol [ISO] on the basis of its effects on biochemical and histological parameters. Twenty four adult male albino rats [180-200 g] were used in this study. They were divided into 4 equal groups of six rats each. Group I was the control group and group II received ISO [85 mg/kg body weight [bw], subcutaneously [S.C.] for two consecutive days to induce myocardial injury. Group III received GB [200 mg/kg bw] orally by gastric gavage daily for 21 days while group IV received GB [200 mg/kg bw] orally daily for 21 days in addition to ISO [85 mg/kg bw], S.C. on the 20th and 21st day from starting GB. After 24 hours, rats were sacrificed and the levels of cardiac marker enzymes [creatine kinase-CK] and its myocardial isoenzyme [CK-MB]] were assessed in serum. Heart specimens were processed for light and electron microscopic examination. Administration of GB before ISO significantly prevented ISO-induced elevation of serum cardiac marker enzymes. Light and electron microscopic findings of the heart pretreated with GB revealed a well preserved normal morphology of cardiac muscle with minimal evidence of myocardial injury when compared to ISO-treated hearts. This study demonstrated that GB had a significant effect in the protection of heart against myocardial injury induced by ISO. This beneficial effect was mostly related to its antioxidant property. The results of the present investigation may trigger an interest towards the use of GB in myocardial infarction

protective role of alpha-Lipoic acid against doxorubicin-induced cardiotoxicity in male albino rats [a light and transmission electron microscopy study]

Doxorubicin [DOX] is an important anti-neoplastic agent. Cardiotoxicity, which mediated by free radicals, is the main side effect of it, leads to induce left ventricular systolic dysfunction and congestive heart failure. The aim of the present study was to investigate the postulated preventive role of alpha-lipoic acid [LA] which is capable of neutralizing a wide variety of free radicals against doxorubicin [DOX]-induced cardiotoxicity. Twenty adult male albino rats were used in this study. They were randomized into four groups [5 rats! group]. Group I [control] received a single intraperitoneal [IP] injection of 3 ml of sterile distilled water. Group II [control LA] received a single IP injection of 3 ml of sterile distilled water and LA [100 mg/kg BW!day] orally for 7 days. Group III [Dox-injected group] received a single IP dose of Dox [1 5mg/kg BW in 3 ml of sterile distilled water]. Group IV received LA as in group II for 5 days before and 2 days after DOX injection. Animals were sacrificed 48 hours after DOX injection. Specimens from the left ventricle of the heart were processed for histological [H and E; Masson's trichrome] and ultra-structural study. Quantitative measurements [cardiomyocyte diameter and color area percentage of collagen] were done using image analyzer [Super eye-Heidi soft]. Group I and II showed no changes. Light microscopic results of group III showed damage and necrosis of cardiomycytes in addition to congestion and mononuclear cellular infiltration. The cardiomyocytic diameter and the surrounding fibrous tissue were significantly increased in this group compared to other studied groups. Ultrastructural results showed loss of cross striation and mitochondrial degeneration. These deleterious changes were significantly improved in group IV. DOX induced cardiotoxicity can be protected by using LA

Histological and scanning electron microscopic study of the effect of cigarette smoke on the heart of male albino rats

Environmental tobacco smoke has been shown to cause heart diseases among non-smokers. Twenty one adult male albino rats were used to investigate the effect of cigarette smoke on the heart and to evaluate the possibility of recovery. Rats were divided into 3 equal groups. Rats of group I were considered as control Rats of group II were exposed to cigarette smoke for 4 weeks, while those of group III were exposed to cigarette smoke for 4 weeks then the exposure was stopped for another 4 weeks. Exposure to cigarette smoke resulted in affection of the coronaries. Some cardiac muscle fibers showed vacuolated cytoplasm, while other showed deeply stained acidophilic cytoplasm and psychotic nuclei. Scanning electron microscopic examination showed that some cardiac muscle fibers appeared necrotic with loss of their normal architecture. There was a decrease in succinic dehydrogenase enzyme activity and in the antiapoptotic Bcl-x [L]protein expression. Stopping the exposure for 4 weeks showed that few cardiac muscle fibers were still affected. Areas of fibrosis were seen between the cardiac muscle fibers in Mallroy stained sections and in the scanning electron microscopic study. There was an increase in scenic dehydrogenase enzyme activity and in the Bcl-x[L] protein expression in the cardiac muscle fibers in group III- that was left for 4 weeks for recovery after 4 weeks of exposure to cigarette smoke- in comparison to those of group II, but was still less than those of the control It is concluded that cigarette smoke affected the cardiac muscle and some of its effects could not be reversible

Impact of trimetazidine on doxorubicin-induced acute cardiotoxicity in mice: a biochemical and electron microscopic study

Doxorubicin [Dox] is an effective broadly used anti-tumor drug. However, its therapeutic success is limited due to the development of acute and chronic cardiotoxicity. Therefore, the purpose of this study was to evaluate the effect of trimetazidine [TMZ] on Dox-induced acute cardiotoxicity in mice using biochemical and electron microscopic approaches. Thirty male mice weighing 30 gm +/- 5gm were used. They were equally divided into 3 groups. Group I represented the control group. Animals of group II, were intraperitoneally [IP] injected with a single dose of Dox [15mg/kg]. In group III, the mice were IP injected with TMZ [2.5mg/kg/d] for 5 days before single injection of the same dose of Dox. Thirty hours after Dox injection, animals were anaesthetized. Blood samples were obtained and serum was separated for measurement of cardiotoxicity indices [creatine phosphokinase isoenzyme [CK-MB], lactate dehydrogenase [LDH] and aspartate aminotransferase [AST]]. Hearts were dissected and each was divided into two halves, one half was used for measurement of myocardial oxidative stress [thiobarbituric acid reactive substance [TBARs], nitrate /nitrite [NOx]] and myocardial antioxidant activity [glutathione [GSH]] level. The other half was processed for electron microscopic study [EM]. In group II, there were significant increase in CK-MB, LDH, AST, TBARs and NOx and a significant decrease in GSH. Electron microscopic examination revealed severe toxic effect on the cardiac muscle in the form of myofibrillar lysis, cytoplasmic vacuoles, oedema, dilatation of sarcoplasmic reticulum, mitochondrial damage, increased number of 2ry lysosomes, widening of the junctions forming the intercalated discs and mononuclear cellular infiltrate between the disorganized cardiac myocytes, whereas group III revealed marked improvement in all biochemical parameters and EM study revealed almost a similar myocardial histological profile to the control group. In conclusion, TMZ ameliorates Dox-induced acute cardiotoxicity in mice by reduction of myocardial oxidative stress and preservation of endogenous antioxidant activity

Effect of immediate and long term amino acids mixture administration on the mechanical performance and apoptotic parameters in isolated rabbit heart during ischemia reperfusion injury

Optimization of the post-ischemic myocardial function remains an elusive goal. The aim of this study was to investigate the effect of supplementation of a specific mixture of amino acids on ischemia and reperfusion induced damage in isolated rabbit heart. Four groups were included in this study: groupl [control group] with isolated hearts perfused with Krebs-Henseleit solution for 2 h, group2 [ischemia-reperfusion group], group 3 [immediate amino-acids group] in which the hearts were perfused with the specific amino-acids mixture added to Krebs solution and group 4 [long term amino-acids group] this group received oral amino-acids mixture for 25 days before decapitation. The isolated hearts of group 2, 3 and 4 were subjected to 30 minutes pre-ischemic perfusion then 30 minutes of ischemia followed by 60 minutes of post-ischemic reperfusion using the Langhendorff technique and cardiac developed pressure, diastolic pressure, contractility index [dp/dt] and heart rate were measured during these phases as well as in group 1 at the end of 2h perfusion. Creatine kinase [CK] was measured in the collected cardiac perfusate at the end of the ischemic phase. Apoptosis was assessed in the heart by measurement of Pas protein level in heart tissue at the end of post-ischemic reperfusion using Elisa and by histological examination of the heart using the light and electron microscopes. Immediate perfusion of the heart with the amino acid mixture in group 3 significantly improved its pre-ischemic developed pressure with a median of 169mmHg compared to that of group 1 [88.5mmHg], group 2 [81mrnHg] and group 4 [99mmHg]. Long term amino acids supplementation in group 4 increased insignificantly its pre-ischemic developed pressure compared to that of group 1 and 2 while it increased significantly group 4 developed pressure with a median of21mmHg compared to that of group 2 [6mmHg] during ischemia.However the developed pressure in group 3 and 4 didn't show any significant change compared to group 1 and 2 during the whole period of post-ischemic reperfusion. Moreover the rise in the diastolic pressure during the post-ischemic reperfusion phase at 10, 30 and 60 minutes was significantly reduced in group 3 with a median of 21.5mmHg at 10 minutes, 19mmHg at 30 minutes and 15.5mmHg at 60 minutes; also it was significantly reduced in group 4 with a median of 13 mmHg at lOmin, 15.75mmHg at 30min and 10,75mmHg at 60min as compared to group 2 diastolic pressure median which was 37.5mmHg at lOmin, 36.25mmHg at 30min and 35.5mmHg at 60min. However there was no significant change in the diastolic pressure during pre-ischemic and ischemic phases in group 3 and 4 compared to group 2. Moreover group 3 and 4 showed no significant change in the pre-ischemic, ischemic and post-ischemic dp/dt contractility index and in the heart rate compared to group 1 and 2. The creatine kinase as a parameter of cardiac ischemia was insignificantly reduced in group 3 and 4 compared to group 2. While Fas protein level as an index of apoptosis showed a significant decrease in group 4 compared to group 2 and 3. Light and electronic microscopic examination revealed a significant improvement in the apoptotic features in group 3 and 4 compared to group 2 with normal nuclear size with condensed chromatin in H and E. Nuclei in group 4 were closer in appearance to those of the control group with normal mitochondria. In conclusion both immediate and long-term amino acids improved the cardiac performance, improved myocytees survival through decreasing Fas activation in cardiac cells during myocardial ischemia-reperfusion and reduced ischemia-reperfusion damage suggesting that mixed amino acids supplementation may be clinically useful as adjunct to conventional anti-ischemic agents.

Sildenafil citrate abuse [II]: an ultrastructural study of the long-term administration of sildenafil citrate in male albino rats

It has been reported that the most affected organs on abusing sildenafil citrate were the testis, retina, brain and heart; and that these changes were dose-and frequency-dependent. This study was set up to elucidate the ultra-structural alterations and hence the mechanism of toxicity in the retinal, cerebral, myocardial and testicular tissues which could result from administration of sildenafil citrate at a dose equivalent to the 100 mg tablet in humans administered at different frequencies. In addition, the study aimed at the assessment of the suitable dose and frequency of administration of the drug. Forty-eight male Wistar albino rats were used; and they were divided into: [n=12] negative control group. [n=36] rats received sildenafil citrate by gavage in a dose of 0.008 mg/g rat. This group was subdivided into 3 subgroups: [n=12] rats received the dose daily. [n= 12] rats received the dose day after day. [n= 12] rats received the dose once per week. The study extended for 18 weeks. Small portions from the brain, retina, heart and testes were excised and processed for electron microscopic examination. Sildenafil citrate causes histopathological alterations in the brain, retina, heart and testis in a dose-and time-dependent manner. It exerts its pathologic effects partly through persistent dilatation and thickening of t he blood vessel walls of the a forementioned tissues; and partly via direct action on the tissue cells and in particular on the mitochondria and rough endoplasmic reticulum

Effect of garlic extract on age-related structural changes in the heart of male albino rat, light and electron microscopical study

Cardiovascular diseases in elderly are mostly ascribable to complications of coronary atherosclerosis, angina pectoris and myocardial infarction. So this study was carried out to detect the senile changes occuring in the structure of the heart of male albino rat, and to evaluate the role of garlic extract in prevention and treatment of these senile changes. Thirty male albino rats were used in this study. They were classified into five groups [six animals each]. Group I: [control group] included adult rats with age [6-9] months. Group II:comprised adult rats[6-9 months age] which were given oral supplementation of garlic extract [50mg/ kg of body weight/ day for 12 weeks]. Group III: consisted of senil rats with ages ranging between 12-18 months. Group IV: included animals of 9 months, which received oral garlic extract [50 mg/ kg of body weight/day for 12 weeks]. Group V: comprised rats with ages 12-18 months, which received oral garlic extract [50 mg/ kg of body weight /day for 12 weeks]. Examination of the histological sections of the heart of senile rats showed patchy areas of degenerative changes in the myocardium. These changes included vacuolation and hyalinization of the cardiac muscle fibres, even areas of necrosis were also detected. Haemorrhage and focal areas of mononuclear cellular infiltration were also noticed between the affected muscle fibres. By electron microscopic examination, there were disorganization and lysis of the myofilaments. The mitochondria appeared degenerated with lysis of its cristea. The nuclei of the affected fibres showed abnormal chromatin distribution. They were surrounded by irregular nuclear membranes. The coronary arteries were dilated and congested. Their tunica media contained foam cells. Increase in the collagen content was seen between the muscle fibres as well as in the wall of the coronary vessles. The heart of animals of group IV[with age 9 months and they were given garlic for 12 weeks], showed the same histological profile as in control sections. However, examination of the sections of the heart of animals of group V [treat ment group] showed improvement in most of the reversible cardiac changes

Light and electron microscopic study on the effect of L-carnitine and B-carotene on the Doxorubicin toxicity in the heart and testes of albino rats

Doxorubicin [Dox] is an anthracycline antibiotic, with a wide spectrum of antitumor activity . Dox as a chemotherapeutic agent is highly toxic . L-carnitine and B-carotene have recently been shown to have high antioxidative properties. This study is an attempt to evaluate the heart and testes responses after Dox injection with or without exogenous L-carnitine or B-carotene protection . Male albino rats, body weight 150-180gm, were divided into nine groups : cont. Dox [therapeutic dose], carnitine, carotene, carnitine plus Dox, carotene plus Dox, Dox [single dose], Dox [single dose] plus carnitine, Dox [single dose] plus carotene .Dox was injected I. P. at a therapeutic dose of 2mg/Kg/b.w. [twice weekly for two weeks], and as a single dose of 15 mg/kg /b.w. Carnitine and carotene were administered I. P. at a dose of 200 mg/kg b.w. and 30 mg/kg b.w. respectively . The experimental period was two weeks . One day after the last dose, the animals were sacrificed and their hearts and testes were dissected . Testicular and cardiac damage were determined histologically and histochemicaly by light and transmission electron microscopes .Dox induced cardiac damage manifested as vacuolar and fatty degeneration, interstitial fibrosis and loss of myoflbrils. Ultrastructurally variation in mitochondrial size and shape with destruction and vacuolization were noticed. On the other hand, Dox induced testicular alterations consisting of cytoplasmic vacuolization, spermatocytes fragmentation and necrosis with large vacuoles in the seminiferous epithelium. Ultrastructurally spermatocytes exhibited ill defined plasma membrane, damaged mitochondria and increase in myelin figure together with abnormal sperms. The histochemical investigations revealed a relative decrease in DNA, protein and PAS reactions, in the cardiac myocytes and in the spermatogenic and interstitial cells of Dox treated rats . However, these alterations became less severe in the protected groups, in both heart and testes suggesting L- Carnitine and B- Carotene as possible protectors against Doxtoxicity

protective effect of electric shock therapy on myotoxicity and cardiotoxicity of Egyptian Naja nigricollis snake venom in albino rat

The Egyptian Naja nigricollis snake is one of the most dangerous snakes. Its danger is attributed to its highly toxic venom which has severe local and systemic reactions. In the present study the use of electric shock [high voltage low amperage] therapy for the treatment of venomous snake bite was investigated. 80 adult male albino rats were divided equally into 4 groups. By intramuscular [IM] injection into the right thigh group 1 and 2 received injection of saline [solvent]. Group 3 and 4 received IM injection of LD50 of the venom [1.15mg/Kg]. After 5 minutes group 21 and 4 received electric shock therapy delivered from stun gun [5 shocks, 2 seconds each with 10 seconds interval] at the site of IM injection. In the different studied groups ECG changes were monitored throughout the study which extends for 2 hours then the rats were sacrificed. The injected muscle and heart were prepared for light and electron microscopic examinations. The histopathological, ultrastructural and ECG changes in this study revealed that the administration of a singe dose [LD50] of the venom [Gr3] induced severe myotoxicity [degeneration, necrosis and swollen mitochondria of the injected muscle], cardiotoxicity [congestion, necrosis and swollen mitochondria of the myofibrfils] with arrythmias, ischemic manifestations and lethality compared to the control [Gr1] and shock [Gr2] trated groups which showed normal patterns. This severe myotoxicity, caradiotoxicity and lethality were markedly reduced in the shock/venom treated group [Gr4]. In conclusion the high voltage shock therapy by Stun gun has a protective effect against the venom induced myotoxicity cardiotoxicity and lethality

Estudo histológico e mesoscópico da valva atrioventricular direita / Histological and mesoscopic study of the atrioventricular right valve

Os estudaram através de corts histológicos e técnica das linhas de fenda os elementos da valva atrioventricular direita, para determinar diferenças morfológicas entre os folhetos considerados ou näo como cúspides. Foram utilizados 10 coraçöes de cadáveres humanos, de indivíduos e de ambos os sexos, provenientes do Serviço de Verificaçäo de Obitos da Escola Paulista de Medicina. As cúspides foram submetidas à técnica habitual para Microscopia Optica Comum. A técnica das linhas de fenda foi realizada com pequena agulha cilíndrica de ponta cônica, imersa em nanquim. Os locais de puncturas foram: superfície atrial, nódulo da cúspide atrioventricular, comissura, cúspide comissural e outras cúspides eventuais. Os resultados mostraram que a disposiçäo das linhas de fenda estariam relacionadas com as inserçöes das cordas tendíneas, e a força resultante que estas exercem sogre as cúspides. Histologicamente, näo há diferenças enquanto a orientaçäo e concentraçäo das fibras colágenas entre as cúspides habituais, comissurais e outras cuspides eventuais

Paragânglios intraganglionares em coraçöes humanos adultos / Intraganglionic paraganglia in adult human hearts

Descrevem-se dois paragânglios intraganglionares observados em coraçöes de homens adultos, aparentemente sadios, que tiveram morte violenta. Os paragânglios assim localizados poderiam relacionar-se ao controle da funçäo ganglionar