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1.
Biol. Res ; 53: 50, 2020. tab, graf
Article in English | LILACS | ID: biblio-1142417

ABSTRACT

BACKGROUND: Acupuncture, a therapy of traditional Chinese medicine, is confirmed to exert the therapeutic action on polycystic ovary syndrome (PCOS). However, the detailed therapeutic mechanisms of acupuncture in PCOS remain ambiguous. In this study, we further investigated whether electroacupuncture (EA) alleviated PCOS-like symptoms in rats via regulating a metabolic regulator, sterol regulatory element binding protein-1 (SREBP1). Methods: The PCOS-like rat model was built by hypodermic injection with dehydroepiandrosterone (DHEA). The rats were subjected to EA intervention (ST29 and SP6 acupuncture points) for 5 weeks. Primary granulosa cells were isolated from control and PCOS-like rats for evaluating insulin resistance, mitochondrial dysfunction and oxidative stress in vitro. RESULTS: The expression of SREBP1 was increased in PCOS-like rats, which was suppressed by EA treatment. In addition, lentivirus-mediated overexpression of SREBP1 restrained EA treatment-induced improvement in pathological changes, serum hormone levels and insulin resistance in rats. In addition, overexpression of SREBP1 repressed insulin-stimulated phosphorylation of insulin receptor ß (IR) and AKT in primary granulosa cells. Moreover, upregulation of SREBP1 further exacerbated mitochondrial dysfunction and oxidative stress in granulosa cells isolated from PCOS-like rats. Mechanically, EA treatment suppressed SREBP1 expression through inducing the activation of AMP-activated protein kinase (AMPK) signaling pathway in PCOS-like rats. CONCLUSION: EA intervention alleviated PCOS-like symptoms in rats via improving IR, mitochondrial dysfunction and oxidative stress through regulating SREBP1, a lipid metabolism regulator. Our findings illuminate the novel protective mechanisms of EA in the treatment of PCOS.


Subject(s)
Animals , Female , Rats , Polycystic Ovary Syndrome/chemically induced , Polycystic Ovary Syndrome/therapy , Insulin Resistance , Electroacupuncture , Oxidative Stress , Sterol Regulatory Element Binding Protein 1/metabolism , Mitochondria/pathology , Rats, Sprague-Dawley , Dehydroepiandrosterone
2.
Int. j. morphol ; 36(4): 1310-1315, Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-975701

ABSTRACT

Exposure to normobaric hyperoxia (NH) is known to increase the production of reactive oxygen species (ROS) by mitochondria. The present study was designed to examine mitochondrial ultrastructure morphological changes in the cortical brainin relation to glutathione peroxidase (GPX) activity and free radicals (FR) productions in brain tissue during hyperoxia exposure. The experimental groups were exposed to NH for 24 and 48 h continuously. Following the exposure periods, animals were sacrificed and cortical tissues were divided randomly into two parts; the first part was processed for the ultrastructural examination and the second was homogenized for GPX and FR determinations. Analysis of variance (ANOVA) showed that the main effects of O2 exposure periods were significant (p<0.05) for GPX and FR. Pair-wise means comparisons showed that NH elevated the average (+SE) GPX activity significantly (p<0.05) from the baseline control value of 5670.99+556.34 to13748.42+283.04 and 15134.19+1529.26 U/L with increasing length of NH exposure period from 24 to 48 h, respectively. Similarly, FR production was increased significantly (p<0.05) to 169.73+10.31 and 185.33+21.87, above baseline control of 105.27+5.25 Unit. Ultrastructure examination showed that O2 breathing for 48 h resulted in giant and swelled mitochondria associated with diluted inner membrane and damaged cristae. These mitochondria pathological alterations were associated with damages of myelin, axonal and cellular organelles. Normobaric-hyperoxia inducts mitochondria oxidative stress (MOS) and the subsequent rise of ROS causes variety of ultrastructure morphological pathological alterations in the organelles of cortical brain cells.


Se sabe que la exposición a la hiperoxia normobárica (HN) aumenta la producción de especies reactivas de oxígeno (ERO) por parte de las mitocondrias. El estudio se diseñó para examinar los cambios morfológicos de la ultraestructura mitocondrial en la corteza cerebral con la actividad de la glutatión peroxidasa (GPX) y la producción de radicales libres (RL) en el tejido cerebral durante la exposición a la hiperoxia. Los grupos experimentales fueron expuestos a HN durante 24 y 48 h continuamente. Tras los períodos de exposición, los animales se sacrificaron y los tejidos corticales se dividieron aleatoriamente en dos partes; la primera parte se procesó para el examen ultraestructural y la segunda se homogeneizó para las determinaciones de GPX y RL. El análisis de varianza (ANOVA) mostró que los efectos principales de los períodos de exposición al O2 fueron significativos (p <0,05) para GPX y RL. Las comparaciones de medias por pares mostraron que la HN elevó la actividad promedio de GPX (+ SE) significativamente (p <0,05) desde el valor de control de línea base de 5670,99 + 556,34 a 13748,42 + 283,04 y 15134,19 + 1529,26 U / L con una mayor duración del período de exposición a HN de 24 a 48 h, respectivamente. De manera similar, la producción de RL se incrementó significativamente (p <0,05) a 169,73 + 10,31 y 185,33 + 21,87, por encima del control de referencia de 105,27 + 5,25 unidades. El examen de la ultraestructura mostró que la respiración de O2 durante 48 h dio lugar a mitocondrias gigantes e hinchadas asociadas con la membrana interna diluida y las crestas dañadas. Estas alteraciones patológicas de las mitocondrias se asociaron con daños de mielina, axones y organelos celulares. La hiperoxia normobárica induce el estrés oxidativo mitocondrial (MOS) y el posterior aumento de las ERO provoca una variedad de alteraciones patológicas y morfológicas en los organelos de las células cerebrales corticales.


Subject(s)
Animals , Rats , Cerebral Cortex/ultrastructure , Hyperoxia/pathology , Mitochondria/pathology , Cerebral Cortex/enzymology , Cerebral Cortex/pathology , Analysis of Variance , Reactive Oxygen Species , Rats, Wistar , Reactive Nitrogen Species , Glutathione Peroxidase/metabolism , Mitochondria/ultrastructure
3.
Acta cir. bras ; 33(8): 652-663, Aug. 2018. graf
Article in English | LILACS | ID: biblio-949377

ABSTRACT

Abstract Purpose: To evaluate histopathological and ultrastructural changes and expression of proteins related to apoptosis CASPASE 3 and XIAP after experimental induction of temporary focal cerebral ischemia (90 minutes) due to obstruction of the middle cerebral artery in alcoholism model. Methods: Forty adult Wistar rats were used, subdivided into 5 experimental groups: control group (C); Sham group (S); Ischemic group (I); Alcoholic group (A); and Ischemic and Alcoholized group (I+A): animals submitted to the same treatment of group A and after four weeks were submitted to focal cerebral ischemia during 90 minutes, followed by reperfusion of 48 hours. Were processed for histopathological analysis and immunohistochemistry (for the protein expression of CASPASE -3 and XIAP). Results: Greater histopathological changes were observed in the animals of groups I and I+A in the three areas analyzed. The neuronal loss was higher in the medial striatum region of the animals of groups I and I + A. The protein expression of CASPASE -3 was higher than that of XIAP in the groups I and I + A for both proteins. Conclusion: The expression of XIAP was slightly higher where the histopathological changes and expression of CASPASE -3 was less evident.


Subject(s)
Animals , Male , Ischemic Attack, Transient/pathology , Alcoholism/pathology , Inhibitor of Apoptosis Proteins/analysis , Caspase 3/analysis , Time Factors , Immunohistochemistry , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Random Allocation , Ischemic Attack, Transient/metabolism , Rats, Wistar , Apoptosis , Middle Cerebral Artery , Microscopy, Electron, Transmission , Alcoholism/metabolism , Edema , Electromyography/methods , Mitochondria/pathology
4.
Braz. j. med. biol. res ; 49(5): e5187, 2016. tab, graf
Article in English | LILACS | ID: biblio-951674

ABSTRACT

The timing and mechanisms of protection by hyperbaric oxygenation (HBO) in hypoxic-ischemic brain damage (HIBD) have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders) were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI) and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm) occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.


Subject(s)
Animals , Male , Female , Rats , Cerebral Cortex/pathology , Hypoxia-Ischemia, Brain/therapy , Hyperbaric Oxygenation/methods , Mitochondria/pathology , Neurons/pathology , Time Factors , Random Allocation , Cerebral Cortex/physiopathology , Rats, Sprague-Dawley , Hypoxia-Ischemia, Brain/physiopathology , Hypoxia-Ischemia, Brain/pathology , Disease Models, Animal , Animals, Newborn , Mitochondria/physiology , Neurons/physiology
5.
Int. j. morphol ; 33(3): 930-935, Sept. 2015. ilus
Article in English | LILACS | ID: lil-762566

ABSTRACT

Oxidative stress is increased in varicose veins. Many studies have implicated oxidative stress in the pathogenesis of infertility causing diseases of the female reproductive tract. The aim of this study was to determine whether varicocele can cause raised levels of reactive oxygen species and denaturation of mitochondrial structure in ovaries of female rats or not. In each experimental study, 15 weaning-age female rats were divided equally in 3 groups: Unilateral Varicose Vein (A), Sham (B) and Control (C) groups. Mitochondrial structure and malondialdehyde levels as a product of lipid peroxidation and Prooxidants-Antioxidants Balance were evaluated 60 days after intervention in proestrus stage. Comparisons between groups were made by the measured test. After 2 months, our results showed that mitochondrial structure ultra-structurally was denatured with histologic examination, malondialdehyde and prooxidants-antioxidants balance levels of left ovaries increased significantly in varicocele group compared to control and sham groups (P0.05). In the right side, malondialdehyde increased significantly, but in prooxidants-antioxidants balance levels, there is no significant differences between groups. The data of control and sham groups were the same. These findings may support the concept that increased levels of malondialdehyde and PAB in varicocele may cause negative effects on fertility, so using antioxidants maybe useful.


El estrés oxidativo aumenta en las venas varicosas. Diversas investigaciones han implicado al estrés oxidativo en la patogénesis de las enfermedades que causan la infertilidad del tracto reproductivo femenino. El objetivo de este estudio fue determinar si el varicocele puede provocar niveles de especies reactivas del oxígeno y la desnaturalización de la estructura mitocondriales en los ovarios de ratas. En cada estudio experimental, cinco ratas hembras en edad de destete se dividieron por igual en 3 grupos: Várices unilateral (A), simulado (B) y control (C). La estructura mitocondrial y los niveles de malondialdehído como un producto de la peroxidación lipídica y el balance pro-oxidantes-antioxidantes (BPA) se evaluaron 60 días después de la intervención en la etapa proestro. Las comparaciones entre grupos se realizaron mediante la prueba de medición. Después de 2 meses, observamos que la estructura mitocondrial se desnaturalizó ultraestructuralmente, los niveles malondialdehído y el balance prooxidantes-antioxidantes de los ovarios izquierdos aumentaron significativamente en el grupo A en comparación con los grupos B y C (P0.05). En el lado derecho, los niveles de malondialdehído aumentaron significativamente, pero el BPA, no mostró diferencias significativas entre los grupos. Los datos de los grupos B y C eran los mismos. Estos hallazgos pueden apoyar el concepto de que el aumento de niveles de malondialdehído y BPA en presencia de varicocele, puede causar efectos negativos sobre la fertilidad, por tanto el uso de antioxidantes puede resultar útil.


Subject(s)
Animals , Female , Rats , Ovary/blood supply , Ovary/pathology , Varicose Veins/pathology , Antioxidants/analysis , Lipid Peroxidation , Malondialdehyde/analysis , Microscopy, Electron , Mitochondria/pathology , Oxidative Stress , Proestrus , Rats, Wistar
6.
Medicina (B.Aires) ; 74(3): 254-258, jun. 2014. ilus
Article in Spanish | LILACS | ID: lil-734375

ABSTRACT

La muerte celular programada y la fibrosis renal son procesos inherentes a la enfermedad renal crónica y, en tal sentido, ha sido recientemente descripta una clara desregulación de la maquinaria respiratoria mitocondrial en pacientes con enfermedad renal crónica asociada con un aumento del estrés oxidativo. Las células tubulares lesionadas vinculadas a los macrófagos intersticiales y miofibroblastos producen citoquinas y factores de crecimiento que promueven un estado inflamatorio, inducen la apoptosis de las células tubulares y facilitan la acumulación de matriz extracelular. La angiotensina II desempeña un papel central en la fibrogénesis renal y conduce a una rápida progresión de la enfermedad renal crónica. Los niveles crecientes de la angiotensina II inducen citoquinas pro-inflamatorias, la activación de NF-kB, moléculas de adhesión, quimiocinas, factores de crecimiento y estrés oxidativo. Toda la evidencia actual sugiere que la angiotensina II aumenta el estrés oxidativo mitocondrial, regula la inducción de apoptosis y condiciona al estado inflamatorio. Por lo tanto, existiría un papel determinante de las mitocondrias y el estrés oxidativo en el proceso inflamatorio renal. Finalmente, esta revisión resume nuestro actual conocimiento acerca de los posibles mecanismos que contribuirían con la apoptosis modulada por la inflamación y/o el estrés oxidativo durante la enfermedad renal crónica. Además, se propone un nuevo concepto de herramientas anti-inflamatorias que regulan el estrés oxidativo mitocondrial lo cual afectaría directamente al proceso inflamatorio y la apoptosis. Esta idea podría tener consecuencias atractivas sobre el tratamiento de patologías inflamatorias renales y de otras afines.


The apoptosis and renal fibrosis are processes inherent to the chronic kidney disease, and consequently a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with chronic renal disease associated to an increase of the oxidative stress. The injured tubular cells linked to the interstitial macrophages and myofibroblasts produce cytokines and growth factors that encourage an inflammatory condition, inducing the apoptosis of the tubular cells and enabling the accumulation of the extracellular matrix. The angiotensin II has a central role in the renal fibrogenesis leading to a rapid progression of the chronic kidney disease. The growing levels of the angiotensin II induce pro-inflammatory cytokines, the activation of NF-kB, adhesion molecules,chemokines, growth factors, and oxidative stress. The current evidence suggests that the angiotensin II increases the mitochondrial oxidative stress, regulates the induction of the apoptosis and conditions the inflammatory process. Therefore the mitochondria and the oxidative stress would play a determinant role in the renal inflammatory process. Finally, this review summarizes our present knowledge regarding the possible mechanisms that would contribute to the apoptosis conditioned by inflammation and/or oxidative stress during the chronic renal disease. Additionally, a new concept of the anti-inflammatory tools is proposed to regulate the mitochondrial oxidative stress that would directly affect the inflammatory process and apoptosis. This concept could have positive consequences on the treatment of renal inflammatory pathologies and related diseases.


Subject(s)
Animals , Humans , Apoptosis/physiology , Mitochondria/metabolism , Mitochondria/pathology , Nephritis/etiology , Oxidative Stress/physiology , Renal Insufficiency, Chronic/etiology , Angiotensin II/metabolism , Cytoprotection , Ergocalciferols/pharmacology , Kidney Cortex/drug effects , Kidney Cortex/pathology , Kidney Tubules/drug effects , Kidney Tubules/pathology , NF-kappa B/metabolism , Nephritis/metabolism , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology , Vitamins/pharmacology
7.
Biocell ; 37(1): 1-9, Apr. 2013. ilus, graf
Article in English | LILACS | ID: lil-694715

ABSTRACT

Cell lines with high passage numbers exhibit alterations in cell morphology and functions. In the present work, C2C12 skeletal muscle cells with either low (<20) or high (>60) passage numbers (identified as l-C2C12 or h-C2C12, respectively) were used to investigate the apoptotic response to H2O2 as a function of culture age h-C2C12. We found that older cultures (h-C2C12 group) were depleted of mitochondrial DNA (mtDNA). When we analyzed the behavior of Bad, Bax, caspase-3 and mitochondrial transmembrane potential, we observed that cells in the h-C2C12 group were resistant to H2O2 induction of apoptosis. We propose serially cultured C2C12 cells as a refractory model to H2O2-induced apoptosis. In addition, the data obtained in this work suggest that mtDNA is required for apoptotic cell death in skeletal muscle C2C12 cells.


Subject(s)
Animals , Mice , Apoptosis/drug effects , Hydrogen Peroxide/pharmacology , Mitochondria/pathology , Myoblasts, Skeletal/pathology , Oxidants/pharmacology , Blotting, Western , Cell Culture Techniques , Cells, Cultured , /metabolism , Cell Division/drug effects , Immunoprecipitation , Microscopy, Fluorescence , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Myoblasts, Skeletal/drug effects , Myoblasts, Skeletal/metabolism , /metabolism
8.
Arq. neuropsiquiatr ; 69(1): 85-90, Feb. 2011. ilus, tab
Article in English | LILACS | ID: lil-598352

ABSTRACT

OBJECTIVE: To study the aging of submucous plexus of the small intestine (jejunum-ileum) of the guinea pigs from the quantitative, structural and ultrastructural perspective. METHOD: Chemical preparations of membrane of the jejunum-ileum of old and young animals with the use of light and electronic microscope. RESULTS: The ganglia of young animals presented between 1 and 56 neurons and the old animals presented from 1 to 30 neurons. The mean density of the ganglia by cm² in the young jejunum-ileum was of 551±36.89 and in the old one 413±11.86. The density of the neurons was 5011±291.11 neurons/cm² average in young animals and 2918±120.70 neurons/cm² in the old ones. The size of the neurons varied in both age groups. The collagen fibers in the ganglia of old animals they were condensed. Degenerated mitochondrias in the interior of the cell were frequent in the old animals. CONCLUSION: In submucous plexus of the jejunum-ileum there is a loss of 38 percent of the neurons with aging.


OBJETIVO: Estudar o envelhecimento do plexo submucoso do intestino delgado (jejuno-íleo) das cobaias do ponto de vista quantitativo, estrutural e ultra-estrutural. MÉTODO: Preparados de membrana do jejuno-íleo de animais jovens e velhos com a utilização de microscopia de luz e eletrônica. RESULTADOS: Os gânglios de animais jovens apresentaram entre 1 e 56 neurônios e os animais velhos apresentaram de 1 a 30 neurônios. A densidade média dos gânglios por cm² no jejuno-íleo jovem foi de 551±36,89 e no velho foi de 413±11,86. A densidade dos neurônios foi de 5011±291,11 neurônios/cm² em média nos animais jovens e 2918±120,70 neurônios/cm² nos velhos. O tamanho dos neurônios variou em ambos os grupos etários. As fibras colágenas nos gânglios de animais velhos estavam mais condensadas. Mitocôndrias degeneradas no interior da célula foram freqüentes nos animais velhos. CONCLUSÃO: No plexo submucoso do jejuno-íleo há uma perda de 38 por cento dos neurônios com o envelhecimento.


Subject(s)
Animals , Guinea Pigs , Male , Ileum/innervation , Jejunum/innervation , Neurons/cytology , Submucous Plexus/anatomy & histology , Age Factors , Aging , Cell Count , Cellular Senescence/physiology , Collagen/analysis , Ganglia, Autonomic/pathology , Ganglia, Autonomic/ultrastructure , Ileum/ultrastructure , Jejunum/ultrastructure , Mitochondria/pathology , Neurons/ultrastructure , Submucous Plexus/ultrastructure
9.
Egyptian Journal of Medical Human Genetics [The]. 2010; 11 (2): 143-151
in English | IMEMR | ID: emr-126680

ABSTRACT

Over recent years it has become apparent that the hepatocyte mitochondrion functions both as a cause and as a target of liver injury. Resultant dysfunction of mitochondria yields deficient oxidative phosphorylation, increased generation of reactive oxygen species, impairment of other metabolic pathways and activation of both necrotic and apoptotic pathways of cellular death. Methods: This study was conducted on 26 children and adolescents with chronic liver disease who presented to or were following up in the Pediatric Hepatology Clinic, Children's Hospital, Ain-Shams University. They were divided into three groups according to the aetiology of liver disease [GI= patients with Wilson's disease [WD], GII=patients with chronic hepatitis C, GIII=patients with chronic liver disease other than Wilson's and chronic hepatitis C].Ultrasound-guided gun liver biopsies were performed, under local anaesthesia for all the 26 patients, using a modified 18-gauge truecut needle. Two liver biopsy cores were taken from each patient. One for light and electron microscopic examinations and the other was immediately immersed in liquid nitrogen to be frozen and used for studying mitochondrial DNA deletions by PCR Liver steatosis was higher in the group of patients with Wilson's disease and other liver disease. Electron microscopic examination of the mitochondria revealed significant mitochondrial pleomorphism in patients with Wilson's disease and patients with chronic hepatitis C infection. Enlarged mitochondria were found to be more prevalent among patients with chronic hepatitis C infection. Three of our patients [11.53%] had mitochondrial DNA deletions. We developed scoring system for mitochondrial affection in our patients, 7 patients [32%] were considered to have mild mitochondrial affection, 9 patients [41%] had moderate mitochondrial affection, while 6 patients [27%] had severe mitochondrial affection. Four of the studied patients had no mitochondrial affection. Conclusion: Mitochondria affection is common in chronic liver disease. This mitochondrial affection might be responsible for some of the chronic liver disease manifestation such as easy fatiguability and steatosis


Subject(s)
Humans , Male , Female , Chronic Disease , Child , Biopsy , Mitochondria/pathology , Histology , Polymerase Chain Reaction , Microscopy, Electron/methods
10.
Article in English | WPRIM | ID: wpr-76616

ABSTRACT

A subset of patients of amyotrophic lateral sclerosis (ALS) present with mutation of Cu/Zn superoxide dismutase 1 (SOD1), and such mutants caused an ALS-like disorder when expressed in rodents. These findings implicated SOD1 in ALS pathogenesis and made the transgenic animals a widely used ALS model. However, previous studies of these animals have focused largely on motor neuron damage. We report herein that the spinal cords of mice expressing a human SOD1 mutant (hSOD1-G93A), besides showing typical destruction of motor neurons and axons, exhibit significant damage in the sensory system, including Wallerian-like degeneration in axons of dorsal root and dorsal funiculus, and mitochondrial damage in dorsal root ganglia neurons. Thus, hSOD1-G93A mutation causes both motor and sensory neuropathies, and as such the disease developed in the transgenic mice very closely resembles human ALS.


Subject(s)
Amyotrophic Lateral Sclerosis/enzymology , Animals , Axons/pathology , Disease Models, Animal , Ganglia, Spinal/pathology , Humans , Mice , Mice, Transgenic , Mitochondria/pathology , Motor Neurons/metabolism , Mutation , Nerve Degeneration/pathology , Sensory Receptor Cells/pathology , Spinal Cord/pathology , Superoxide Dismutase/genetics
11.
Acta cir. bras ; 23(supl.1): 72-76, 2008. graf
Article in English | LILACS | ID: lil-483127

ABSTRACT

PURPOSE: Hyperbaric oxygen therapy (HOT) consists of intermittent inhalations of 100 percent oxygen at a pressure higher than 1 atm. It is an important adjuvant therapy in pathological processes like soft tissue infections, radiation injury, gas gangrene, osteomyelitis and decompressive diseases. Cisplatin, a potent antineoplastic drug, widely used in cancer therapy is highly ototoxic causing bilateral, irreversible damage to the hearing of high frequency sounds (4-8 KHz). OBJECTIVE:This experimental study conducted at the Faculty of Medicine of Ribeirao Preto, University of Sao Paulo aims to evaluate Hyperbaric Oxygen Therapy as an otoprotection agent against drug toxicity. METHODS: Albino guinea pigs were divided into two groups: in Group A, 5 animals (10 cochlea) received cisplatin, i. p., 8.0 mg/kg/day during three days and afterwards were submitted to HOT; in Group B, 3 animals (6cochlea) received cisplatin, i. p. 8.0mg/kg/day during three days. Guinea pigs were evaluated by acoustic otoemissions (AOE) and scanning electron microscopy (SEM). RESULTS: Group B animals showed loss of auditory functions as measured by AOE and distorted outer hair cells by SEM. In Group A, outer hair cells shown by SEM images were mostly preserved. CONCLUSION: It is presumed that Hyperbaric Oxygen Therapy has a protector effect against cisplatin ototoxicity.


INTRODUÇÃO: A Oxigenoterapia hiperbárica (OHB) envolve a inalação de oxigênio a 100 por cento sob uma pressão maior que 1 atm. E um importante modo de terapia adjuvante para processos patológicos, tais como: infecção de partes moles, lesões actínicas, gangrena gasosa, osteomielite e doença descompressiva. A cisplatina e uma potente droga antineoplásica largamente utilizada para o tratamento de câncer. A ototoxicidade e um importante efeito colateral desta droga, causando dano irreversível, bilateral, na capacidade de ouvir sons de alta freqüência (4 - 8 KHz). Este estudo experimental, realizado na Faculdade de Medicina de Ribeirao Preto da Universidade de São Paulo nos anos de 2005 e 2006. Objetivo: Avaliar o papel da Oxigenoterapia Hiperbárica como agente otoprotector contra a toxicidade de drogas. MÉTODOS: Cobaias albinas divididas em 2 grupos Grupo A: com 5 cobaias (10 cócleas) que receberam cisplatina 8,0 mg/kg/dia, via intraperitoneal por 3 dias, submetidas posteriormente a OHB. Grupo B: com 3 cobaias (6 cócleas) que receberam cisplatina 8,0 mg/kg/dia, via intraperitoneal por 3 dias. As cobaias foram avaliadas através de otoemissões acústicas (OEA) e por microscopia eletrônica de varredura (MEV). Resultados: Encontramos no grupo B perda da função auditiva medida pela OEA e distorção das células ciliares externas a MEV. No grupo A, a MEV as células ciliares externas foram preservadas em sua grande maioria. CONCLUSÃO: Assim podemos supor que a Oxigenoterapia Hiperbárica tem um efeito otoprotetor contra a ototoxicidade induzida pela cisplatina.


Subject(s)
Animals , Guinea Pigs , Antineoplastic Agents/toxicity , Cisplatin/toxicity , Cochlea/drug effects , Hyperbaric Oxygenation , Hearing Loss/prevention & control , Cell Respiration/drug effects , Cochlea/pathology , Disease Models, Animal , Hair Cells, Auditory/drug effects , Hair Cells, Auditory/pathology , Hearing Loss/chemically induced , Mitochondria/drug effects , Mitochondria/pathology , Oxygen Consumption/drug effects
12.
West Indian med. j ; 56(6): 481-486, Dec. 2007. tab, ilus, graf
Article in English | LILACS | ID: lil-507261

ABSTRACT

Serum copper levels must be maintained between very strict limits for the maintenance of good health. High levels have recently been linked to Alzheimer's disease while low levels during pregnancy cause enzootic ataxia (swayback disease) in offspring. In this study, we investigated the prolonged effect of serum copper that was maintained at and around 0.5 ppm, the level presently regarded as safe. Pregnant sheep and rabbits in the last trimester (1-4 weeks) of pregnancy were treated with the copper chelator ammonium tetrathiomolybdate (ATM). Treatment was continued until the young were one month old at which time the animals were sacrificed Serum copper levels of the parents and offspring were monitored by atomic absorption. The difference spectra (400-630 nm) was examined and SDS PAGE was used to evaluate the protein composition of the brain mitochondria. The anatomy of the midbrain was also studied. Although the young sheep and rabbits from the ATM-treated mothers showed no visible signs of disability or swayback disease, the midbrain of those young animals with serum copper between 0.3-0.9 ppm showed evidence of vacuolation, cavitation and chromatolysis. In contrast, the difference spectra and the protein composition of the brain mitochondria from these animals were all normal. These results suggest that although animals may appear normal and exhibit some normal biochemical markers, serum copper in the region of 0.5 ppm may not be safe for some breeds of sheep or rabbits. It is possible that a similar situation applies to man.


Los niveles séricos cúpricos tienen que ser mantenidos dentro de límites muy estrictos, si se quiere tener una buena salud. Los altos niveles de cobre han sido asociados recientemente con la enfermedad de Alzheimer, mientras que los niveles bajos durante el embarazo causan ataxia enzoótica (swayback) enla descendencia. En este estudio investigamos el efecto prolongado del cobre sérico mantenido a 0.5 ppm ó alrededor de 0.5 ppm – el nivel considerado seguro actualmente. Ovejas y conejas preñadas, en el último trimestre (1-4 semanas) de gestación, fueron tratadas con el quelante del cobre conocido como tetratiomolibdato de amonio (TM). El tratamiento continuó hasta que las crías tuvieron un mes,momento en el que los animales fueron sacrificados. Los niveles séricos cúpricos de los progenitores y la progenie fueron monitoreados mediante absorción atómica. Se examinaron los espectros de diferencia (400– 630 nm). Se usó la técnica de SDS-PAGE para evaluar la composición proteica de lasmitocondrias cerebrales. También se estudió la anatomía del mesencéfalo. Aunque la anatomía de las crías de ovejas y conejas madres tratadas con TM no mostraron señales visibles de discapacidad o enfermedad swayback, el mesencéfalo de estas crías con cobre sérico entre 0.3–0.9 ppm, mostróevidencias de vacuolación, cavitación y cromatolisis. En contraste con ello, los espectros de diferencia y la composición proteica de las mitocondrias del cerebro de estos animales, fueron todos normales. Estos resultados sugieren que aunque los animales puedan parecer normales y presentar marcas bioquímicas normales, el cobre sérico en el rango de 0.5 ppm, puede no ser seguro para algunas crías de ovejas y conejos. Es posible que una situación similar se aplique al ser humano.


Subject(s)
Humans , Animals , Female , Pregnancy , Rabbits , Copper/blood , Mesencephalon/metabolism , Mesencephalon/pathology , Copper/antagonists & inhibitors , Mitochondria/metabolism , Mitochondria/pathology , Molybdenum/administration & dosage , Molybdenum/adverse effects , Sheep , Spectrophotometry, Atomic , Vacuoles/metabolism , Vacuoles/pathology
13.
Biocell ; 27(2): 213-224, Aug. 2003.
Article in English | LILACS | ID: lil-384241

ABSTRACT

CG 10-248 (3,4-dihydro-2,2-dimethyl-9-chloro-2H-naphtho[1,2b]pyran-5,6-dione; CG-NQ), a beta-lapachone analogue, modified the ultrastructure of rat hepatocytes, as demonstrated by light and electron microscopy. After 4 h incubation with 100 microM CG-NQ, the following effects were observed: (a) nuclear chromatin condensation; (b) chromatin fragmentation; (c) displacement of mitochondria, concentrated around the nucleus; (d) disruption or expansion of mitochondrial outer or inner membranes, respectively; (e) displacement and alteration of endoplasmic reticulum (rough and smooth); (f) decrease of microvilli; (g) blebbing of plasma membrane and production of apoptotic bodies formed by folding of plasma membrane fragments around mitochondria or peroxysomes; and (h) production of hydrogen peroxide. Expression of such effects varied according to hepatocyte samples and taken together strongly support an apoptotic action of CG-NQ dependent on reactive oxygen species.


Subject(s)
Humans , Male , Apoptosis/drug effects , Hepatocytes/drug effects , Naphthoquinones/pharmacology , Naphthoquinones/toxicity , Apoptosis/physiology , Cells, Cultured , Chromatin/drug effects , Chromatin/pathology , Cell Surface Extensions/drug effects , Cell Surface Extensions/pathology , Cell Surface Extensions/ultrastructure , DNA Fragmentation/drug effects , DNA Fragmentation/physiology , Hepatocytes/metabolism , Hepatocytes/ultrastructure , Microscopy, Electron , Intracellular Membranes/drug effects , Intracellular Membranes/pathology , Intracellular Membranes/ultrastructure , Microvilli/drug effects , Microvilli/pathology , Microvilli/ultrastructure , Mitochondria/drug effects , Mitochondria/pathology , Mitochondria/ultrastructure , Hydrogen Peroxide/metabolism , Rats , Rats, Wistar , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/pathology , Endoplasmic Reticulum/ultrastructure
14.
Article in English | WPRIM | ID: wpr-140415

ABSTRACT

Although light microscopic features of muscle are not pathognomonic in most cases of myasthenia gravis (MG), careful examination of neuromuscular junction by electron microscopy (EM) can reveal important clues for this disease. We report here a case of MG confirmed by EM study to emphasize that tissue diagnosis is still the best adjuvant to confirm the diagnosis. An 18-year-old female visited our hospital complaining of progressive muscle weakness for 3 years. She had difficulty in running, going upstairs and doing routine activities. Symptoms were aggravated with continuous work and resolved after rest. She had weakness of bilateral masseter and facial muscles and proximal portions of extremities without definite diurnal variation. Electromyography showed myopathic changes in proximal muscles of extremities. MG was considered but tensilon test was equivocal. Repetitive nerve stimulation tests revealed 20-30 percent decrease in responses to low and high rate stimulation. Muscle biopsy revealed selective type 2 atrophy. Ultrastructurally, abnormalities of neuromuscular junctions, i.e., wide primary synaptic cleft, and wide and shallow secondary synaptic clefts with mild myopathic features were present. These findings were pathognomonic for MG. Later, her symptoms were improved completely 3 months after thymectomy. The histologic finding of thymus was follicular hyperplasia.


Subject(s)
Adolescent , Biopsy , Female , Humans , Microscopy, Electron , Mitochondria/ultrastructure , Mitochondria/pathology , Muscle, Skeletal/ultrastructure , Muscle, Skeletal/pathology , Muscle, Skeletal/enzymology , Myasthenia Gravis/pathology , Myofibrils/ultrastructure , Myofibrils/pathology , Myosins/analysis , Neuromuscular Junction/ultrastructure , Neuromuscular Junction/pathology
15.
Article in English | WPRIM | ID: wpr-140414

ABSTRACT

Although light microscopic features of muscle are not pathognomonic in most cases of myasthenia gravis (MG), careful examination of neuromuscular junction by electron microscopy (EM) can reveal important clues for this disease. We report here a case of MG confirmed by EM study to emphasize that tissue diagnosis is still the best adjuvant to confirm the diagnosis. An 18-year-old female visited our hospital complaining of progressive muscle weakness for 3 years. She had difficulty in running, going upstairs and doing routine activities. Symptoms were aggravated with continuous work and resolved after rest. She had weakness of bilateral masseter and facial muscles and proximal portions of extremities without definite diurnal variation. Electromyography showed myopathic changes in proximal muscles of extremities. MG was considered but tensilon test was equivocal. Repetitive nerve stimulation tests revealed 20-30 percent decrease in responses to low and high rate stimulation. Muscle biopsy revealed selective type 2 atrophy. Ultrastructurally, abnormalities of neuromuscular junctions, i.e., wide primary synaptic cleft, and wide and shallow secondary synaptic clefts with mild myopathic features were present. These findings were pathognomonic for MG. Later, her symptoms were improved completely 3 months after thymectomy. The histologic finding of thymus was follicular hyperplasia.


Subject(s)
Adolescent , Biopsy , Female , Humans , Microscopy, Electron , Mitochondria/ultrastructure , Mitochondria/pathology , Muscle, Skeletal/ultrastructure , Muscle, Skeletal/pathology , Muscle, Skeletal/enzymology , Myasthenia Gravis/pathology , Myofibrils/ultrastructure , Myofibrils/pathology , Myosins/analysis , Neuromuscular Junction/ultrastructure , Neuromuscular Junction/pathology
16.
Indian J Biochem Biophys ; 1999 Aug; 36(4): 266-71
Article in English | IMSEAR | ID: sea-27988

ABSTRACT

The endogenous production of H2O2 in isolated rat intestinal mitochondria and oxidant induced damage to mitochondria were examined. There was an appreciable amount of H2O2 production in presence of succinate, glutamate and pyruvate, while the presence of rotenone with succinate further increased production. Superoxide generated by the X-XO system induced membrane permeability transition (MPT), calcium influx, lipid peroxidation and changes in membrane fluidity in mitochondria. A decreased mitochondrial ATPase activity and uncoupling of respiration was also observed. Spermine inhibited swelling induced by X-XO and also blocked the calcium influx and reversed the membrane fluidity changes.


Subject(s)
Animals , Intestines/ultrastructure , Mitochondria/pathology , Oxidative Stress , Rats , Reactive Oxygen Species
18.
Acta bioquím. clín. latinoam ; 25(1): 19-24, mar. 1991. ilus, tab
Article in Spanish | LILACS | ID: lil-100835

ABSTRACT

Visones de un criadero que recibian alimentos, sobre la base de restos de pescado, evidenciaron un significativo aumento en su mortalidad, presencia de canceres hepaticos y alteraciones renales revelables histologicamente. Esos efectos fueron atribuibles a presencia, en el alimento, de dimetilnitrosamina (NDMA), en concentraciones 1,8 ug/g. En este trabajo se estudia en detalle el efecto de la NDMA sobre el rinon del vison. Visones que fueron tratados ip con NDMA(7 mg/kg en sol. fis.), mostraron dano evidenciable ultraestructuralmente en la corteza renal. El dano fue mayor en los tubulos proximales, que en los distales, pero era de naturaleza similar. Las celulas epiteliales tubulares de los animales intoxicados mostraron: a)Condensacion de la cromatina nuclear y dilatacion de la membrana perinuclear. b)Marcada hinchazon mitocondrial y ruptura de sus crestas con perdida de contenida de la matriz mitocondrial. c)Despegue de ribosomas y dilatacion del reticulo endoplasmico. d)Aumento del numero y tamano de las vacuolas autofagicas. e)Aparicion de gotas lipidicas en el citiplasma. En contraste con lo previamente establecido, para el caso de cancer hepatico del vison, el mecanismo del dano renal por NDMA no se pudo correlacionar directamente con la union de metabolitos reactivos de esta a proteinas o acidos nucleicos o la biotransformacion microsomal o mitocondrial de la NDMA o formaldehido. No obstante, el rinon biotransforma la NDMA a CO2, pero lo hace 3-4 veces menos intensamente que el rinon de rata. Los resultados sugeririan la presencia, en el caso del dano renal por NDMA, de mecanismos distintos de accion, a los habitualmente aceptados como responsables del dano hepatico o el renal en otras especies. Alternativamente, el dano renal puede deberse a dano hepatico concomitante


Subject(s)
Animals , Male , Female , Rats , Dimethylnitrosamine/adverse effects , Mink , Mitochondria/pathology , Kidney/metabolism , Kidney Tubules/pathology , Fishes , Liver , Liver/ultrastructure , Meat , Mitochondria/ultrastructure , Kidney , Kidney/ultrastructure , Sodium Nitrite/adverse effects , Kidney Tubules/ultrastructure
19.
Neuroeje ; 3(3): 117-24, 1985. ilus
Article in Spanish | LILACS | ID: lil-38196

ABSTRACT

Se describe el caso de un paciente masculino de 11 años referido por ataxia, ptosis palpebral y problemas de aprendizaje. Luego de efectuar diversos estudios se diagnostica un síndrome de Keerns - Sayre, enfermedad descrita en 1958 y que comprende una gran cantidad de manifestaciones clínicas, dada su naturaleza multisistémica. El problema básico reside en la estructura de las mitocondrias. Se completa el reporte con una relación monográfica sobre el tema


Subject(s)
Child , Humans , Male , Kearns-Sayre Syndrome/diagnosis , Mitochondria/pathology
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