Degenerative Changes In Mitochondria Research Articles

FEATURES OF RELATIONSHIPS BETWEEN ULTRASTRUCTURES OF THE ENERGY CAPABILITY PROFILE OF FOLLICULAR THYROCYTES IN THE CORRECTION OF ALIMENTARY IODINE DEFICIENCY WITH A LOW DOSE OF ORGANIC AND INORGANIC IODINE


 The considerable spread of dietary iodine deficiency and the medical and social significance of the pathology caused by it justifies the use of mathematical methods to study the specific activity of follicular thyrocytes when correcting the manifestations of hypothyroidism with iodine of different chemical nature. The aim of this research was to examine the features of the relationship between the energy direction ultrastructures of follicular thyrocytes when taking a low dose of organic and inorganic iodine under the conditions of dietary iodine deficiency. The study was conducted on the thyroid glands of 40 white nonlinear male rats with an initial body weight of 140-160 g using electron microscopy, linguistic description of electronograms, the method of semi-quantitative analysis of electronograms, the method of specifying the profiles of special capabilities of hormone-poietic cells, and correlation analysis. On the basis of designing the correlation portraits, the interpretation of the results from the standpoint of cytophysiology was carried out. Analysis of correlation portraits of the energy capability profile of follicular thyrocytes showed that low iodine intake of both drugs reduced the functional stress caused by iodine deficiency. This was indicated by changes in mitochondria: an increase in their number and ribosomes on their cristae, a decrease in degenerative changes, granular structure of the matrix, restoration of topographic connection with the rough endoplasmic reticulum and Golgi apparatus. Normal iodine intake was characterized by very high (r=1.000) connections between the moderate number of mitochondria with their well-defined cristae and between the granular structure of the mitochondrial matrix with no degenerative changes in the mitochondria. When consuming inorganic iodine for the energy supply of follicular thyrocytes at a level sufficient for their activity, a very high (r=1.000) connection of round shape mitochondria with the existing topographic connection of mitochondria, rough endoplasmic reticulum, and Golgi apparatus was indicated and high (r=0.881) association of moderate numbers of mitochondria with medium size mitochondria. Nevertheless, in a certain part of thyrocytes, such signs of functional stress as degenerative changes in mitochondria and their cristae, disturbance of topographic interaction of mitochondria with rough endoplasmic reticulum, and Golgi apparatus remained. The studies have established a multilevel adaptation of follicular thyrocytes to function in adverse conditions while enriching the diet with a low dose of iodine increases their energy capability. Organic iodine consumed in low doses, more than inorganic iodine increases the energy supply of follicular thyrocytes’ specific activity.

Cytopathological Effects of Almix Herbicide on Gill, Liver and Kidney of Oreochromis niloticus under Field and Laboratory Conditions

Objective: Present study was aimed to study the cytopathological effects of almix herbicide in Indian freshwater teleost, Oreochromis niloticus (Linn.) both under field and laboratory exposure. Methods: O. niloticus (Linn.) was exposed to almix herbicide at sublethal concentrations of 8 g/acre and 66.67 mg/L under field and laboratory conditions respectively for 30 days. Field experiment was performed in cage, submerged in the field pond. Cytopathological study both through light and electron microscopic (scanning electron microscopy and transmission electron microscopy) observations were based on gill, liver and kidney. Results: Histopathological observations revealed hypertrophy and proliferation in gill epithelium, curling and fusion of secondary gill lamellae (SGL), distortion in chloride and pillar cells under laboratory experiment. Scanning electron microscopy displayed severe loss of normal array of concentric microridges, swelling of microridges, damage in epithelial cells and appearance of vacuoles on the stratified epithelium, while loss of regular pattern of microridges were observed under field condition. Transmission electron microscopic study of gill showed severe damages which included degenerative changes in mitochondria, cellular vacuolation, damage in tubule vascular system, presence of lipid droplets, elongated nucleus, but in case of field experiment dilated mitochondria and cytoplasmic vacuolation were more prominent. Degenerative hepatopancreas, necrosis in hepatocytes, severe cytoplasmic vacuolation and disarrangement of hepatic cords in liver of O. niloticus were prominent seen under light microscopy in the laboratory condition, but in field condition elongated hepatocytes with increased nuclei and vacuolation in cytoplasm of hepatocytes were prominent, while TEM study showed degeneration in mitochondria, dilation in rough endoplasmic reticulum, damage in nucleus and appearance of cytoplasmic vacuolation in hepatocytes under laboratory condition. In kidney, degenerative changes in PCT and DCT, shrinkage of glomerulus, vacuolation in the haematopoietic tissues and excess fat deposition were notable changes. In TEM study necrosis in nucleus, severe vacuolation, appearance of endoplasmic reticulum as whorl pattern, degeneration in mitochondria in kidney were serious after almix exposure. Conclusion: Present study claimed the more profound responses under laboratory condition compared to field and different significant marked changes in these two conditions were prominent. Therefore, these responses in gill, liver and kidney of O. niloticus could be considered as potential of exposure of agrochemicals.

Histopathological and ultramicroscopical changes in gill, liver and kidney of Anabas testudineus (Bloch) after chronic intoxication of almix (metsulfuron methyl 10.1%+chlorimuron ethyl 10.1%) herbicide

Present study aimed to investigate the effects of almix herbicide on histopathological and ultrastructural changes in freshwater teleostean fish, Anabas testudineus (Bloch) under field and laboratory conditions with a dose of 8g/acre and 66.7mg/L respectively for 30 days. In field experiment fish species were reared in special type of cage submerged in pond. Cellular alterations of the concerned organs namely gills, liver and kidney were observed through light, scanning and transmission electron microscopy (SEM and TEM). Gill showed hypertrophy and oedema in secondary gill epithelium, and epithelial lifting under laboratory condition but in field condition hyperplasia was prominent. SEM study revealed necrosis, hyperplasia, excessive secretion of mucus and loss of microridges; while TEM study depicted degenerative changes in mitochondria and chloride cells and severe cytoplsmic vacuolation but the changes were comparatively less under field study. In liver, damage in acinar cells of hepatopancreas, degenerative changes in zymogen granules and detachment of hepatopancreatic acinar cells under laboratory condition were the serious changes, but in field condition fatty deposition is prominent. TEM study depicted dilated, degranulated and vesiculated rough endoplasmic reticulum, dilation and swelling of mitochondria and vacuolation in hepatocytes, but under field condition dilation of mitochondria and appearance of vacuolation were well marked. Kidney showed shrinkage of glomerulus, damaged and hypertrophied proximal convoluted tubule, loss of haematopoietic tissues under light microscopy; while ultrastructural changes like degenerative changes in mitochondria, deformed nucleus, dilation, fragmentation and vesiculation of rough endoplasmic reticulum, severe vacuolation in cytoplasm and necrosis were of very serious concern under laboratory condition, but in field condition epithelial cells showed less damage. Responses depicted that symptoms of lesions were more pronounced under laboratory than field condition and the degree of responses in different tissues were different under these two conditions. Therefore, evaluation of these histopathological lesions in concerned tissues may be established as symptomatic indicators for toxicity study in aquatic ecosystem.

The SIRT6 deacetylase regulates aging‐associated heart failure by modulating IGF‐Akt signaling at the level of chromatin.

The sirtuin SIRT6 is a chromatin bound enzyme which is implicated in extending lifespan of animals. However, the mechanism of longevity effects of SIRT6 is not known. This study was undertaken to test the effect of SIRT6 on the development of cardiac hypertrophy and heart failure. SIRT6 levels were significantly reduced in mouse aging hearts, and in hearts subjected to develop cardiac hypertrophy by trans‐aortic constriction or agonist infusion. To directly test the effect of SIRT6 deficiency on the development of cardiac hypertrophy, we deleted SIRT6 in the adult mouse heart (SIRT6KO). SIRT6KO mice spontaneously developed cardiac hypertrophy with sever fibrosis and degenerative changes in mitochondria. These hearts also expressed higher levels of aging associated cytoskeletal proteins, fibrotic markers and apoptotic genes. SIRT6KO hearts also had increased expression of several IGF‐Akt signaling related genes. Conversely, transgenic mice having cardiac specific overexpression of SIRT6 were resistant to develop cardiac hypertrophy, and these hearts had attenuated expression of aging associated proteins and IGF‐Akt signaling related genes. ChIP analyses reveled that SIRT6 regulates IGF‐Akt signaling genes by deacetylating H3K9. These data thus indicated that SIRT6 protects the heart from developing hypertrophy by blocking expression of IGF‐Akt signaling related genes at the level chromatin.

Disruption of mitochondrial respiration by melatonin in MCF-7 cells.

Clinical and laboratory studies have provided evidence of oncostatic activity by the pineal neurohormone melatonin. However, these studies have not elucidated its mechanism of action. The following series of MCF-7 breast tumor cell studies conducted in the absence of exogenous steroid hormones provide evidence for a novel mechanism of oncostatic activity by this endogenous hormone. We observed a 40--60% loss of MCF-7 cells after 20-h treatment with 100 nM melatonin, which confirmed and extended previous reports of its oncostatic potency. Interestingly, there were no observed changes in tritiated thymidine uptake, suggesting a lack of effect on cell cycle/nascent DNA synthesis. Further evidence of a cytocidal effect came from morphologic observations of acute cell death and autophagocytosis accompanied by degenerative changes in mitochondria. Studies of mitochondrial function via standard polarography revealed a significant increase in oxygen consumption in melatonin-treated MCF-7 cells. Enzyme-substrate studies of electron transport chain (complex IV) activity in detergent permeabilized cells demonstrated a concomitant 53% increase (p < 0.01) in cytochrome c oxidase activity. Additional studies of succinate dehydrogenase activity (complex II) as determined by reduction of (3-4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide demonstrated a significant increase (p < 0.05) in melatonin-treated cells and further confirmed the accelerated ET activity. Finally, there was a 64% decrease (p < 0.05) in cellular ATP levels in melatonin-treated cells. The G-protein-coupled melatonin receptor antagonist luzindole abrogated the cytotoxic and mitochondrial effects. These studies suggest a receptor-modulated pathway of cytotoxicity in melatonin-treated MCF-7 tumor cells with apparent uncoupling of oxidative phosphorylation.

Age-dependent covenant DNA alterations (I-compounds) in rat liver mitochondrial DNA

Rat liver mitochondrial (mt) DNA was investigated for the presence of I-compounds, a recently discovered type of DNA modifications which is detected and measured via 32P-postlabeling. These DNA modifications were previously shown to accumulate in an age-dependent manner in total cellular DNA of various tissues of untreated rodents. In the present work, mt DNA of 1-, 3-, 6-, and 9-month-old female Sprague-Dawley rats was found by 32P-postlabeling also to contain I-compounds that increase with age. Most of the I-compounds were identical for mt and nuclear (nu) DNA. A cluster of 2 non-polar I-spots (termed M-compounds) was mitochondria-specific and increased about 8-fold from 1 to 9 months, attaining a RAL value of 44 X 10(-9) or 1 modification in 2.3 X 10(7) DNA nucleotides at 9 months. Quantitative differences between chromatographically identical spots were seen mainly for a low-polarity fraction of I-compounds, which exhibited 2 times higher overall levels in mt DNA versus nu DNA over the age range studied. Total I-compound levels increased during this time 6.9- and 5.1-fold in nuclei and mitochondria, respectively. The M-compound level was close to 10% of total mt DNA I-compound levels. M-compounds may conceivably be derived from potentially DNA-reactive electron carriers of the mt electron-transport chain, while I-compounds common to both mt and nu DNA presumably originate in extramitochondrial sources. The similarity of mitochondrial and nuclear I-compound profiles and amounts implies possible regulatory mechanisms in I-compound formation and repair. Mt DNA maps showed additional 32P-labeled material which may have been associated with DNA damage caused by oxygen free radicals known to be generated by the mt electron-transport chain. Age-dependent increases of mt DNA modifications are potentially related to mt mutations and may be linked to age-related degenerative changes in mitochondria.

Changes in motor end-plates resulting from muscle fibre necrosis and regeneration: A light and electron microscopic study of the effects of the depolarizing fraction (cardiotoxin) of Dendroaspis jamesoni venom

The venom of Dendroaspis jamesoni (Jameson's mamba) was fractionated by column chromatography. One of the fractions (F8) caused rapid depolarization of muscle fibres when tested in vitro, an action similar to that of “cardiotoxins” of other snake venoms. A single injection of 20 μg of the depolarizing fraction was made directly into the muscles of one hindleg in mice. Light and electron microscopic studies were made of muscle fibres and motor end-plates of animals allowed to survive from 30 min to 6 months after the injection. The depolarizing fraction caused rapid and severe disorganization of the internal structure of muscle fibres affecting slow and fast types of fibre equally severely. Muscle fibres were affected in segments and not along their entire length. Early changes were the disappearance of Z-lines, the dissolution of myofilaments and degenerative changes in mitochondria, but the basement membranes of the muscle fibres remained intact. Regeneration of muscle took place rapidly and was usually complete within 2 to 3 weeks but centrally-placed nuclei, rows of nuclei and malorientation of myofibrils including the formation of striated annulets remained as permanent abnormalities and were used as indicators of where necrosis had occurred. Myelinated axons and motor nerve terminals were normal in appearance and contained abundant vesicles and mitochondria even when the muscle fibres they innervated were necrotic. The axonal terminals became enclosed within Schwann cell processes. After muscle regeneration was complete the end-plate morphology remained abnormal. With light microscopy the end-plates were seen as aggregations of sub-units, each aggregation being limited to a single muscle fibre and innervated by a single pre-terminal myelinated axon. The electron-microscopic appearance of the motor end-plates also remained abnormal and there was a striking absence of post-synaptic folds of the sarcolemmal membrane. The observations made in these experiments indicate that the cardiotoxin selectively damages muscle fibres leaving the motor innervation structurally intact and also show how morphological abnormalities may develop in motor end-plates as a result of a primary lesion of the muscle fibre. The appearances are similar to those occurring in the innervation of muscle in human myopathies. The absence of branching of preterminal axons and of sprouting from axon terminals is in contrast to the changes found in human and experimental conditions in which there is known to be a disorder of the lower motor neurone.

Formation and degradation of mitochondria in the cell

Prolonged deaeration ofSaccharomyces cerevisiae cells results in degenerative changes in mitochondria which can be revealed when measuring the enzymic activities of the respiratory chain in isolated organelles and by electron microscope examination of the cells. The same changes are observed after a 3-h incubation of the cells with cyanide or carbonyl cyanide, m-chlorophenyl hydrazone in aerobic conditions. These results suggest the important role of oxidative phosphorylation in the maintenance of the integrity of mitochondria in the cell. The sensitivity of yeast mitochondria to anaerobiosis and cyanide changes as the culture grows. Mitochondria are especially labile during the early exponential growth phase when their respiratory system and structure are not fully formed. Possible reasons for and the mechanism of degradation of mitochondriain vivo are discussed.

Pathology of Radiostrontium Exposure in Cats

Thirty-three cats of two age groups were fed one of three dosage levels of ${}^{89}{\rm Sr}$ for 30 days. Twenty-four died or were killed before 107 days after the experiment was started. Mortality and bone marrow lesions were dose related. All cats had varying degrees of a hemorrhagic disease with hemorrhages most commonly observed in the heart, subcutis and intestines. Histologically, bone marrows of cats dying before 35 days postexposure were depleted of cells. Those dying later had cellular marrows composed predominantly of erythropoietic precursors. Myelofibrosis was seen in 5 cats and myeloid metaplasia, primarily in lymph nodes, developed in 6 cats. Dysplastic lesions occurred in the epiphyseal plate and metaphysis of long bones. Other lesions included atrophy of the thymus and lymphoid tissues and bacterial lesions in several tissues. Ultrastructural studies of bone marrow of 4 cats revealed degenerative changes in mitochondria of plasma cells and the presence of abnormal erythrocyte precursors. C...