CC BY
17Received by the Editor 12.03.2020
IRSTI 76.29.62
UDC 614.876+616.45
RADIATION-INDUCED ADRENAL GLAND INJURY
D. Shabdarbaeva, N. Chaizhunusova, D. Uzbekov, S. Auleisova, B. Ruslanova, S. Uzbekova, M. Apbasova
Non-profit incorporate institution «State Medical University», Semey city, Kazakhstan
According to literary sources, the adrenal glands are vital organs involved with their hormones in a variety of metabolic processes. It is worth noting that the structural-functional changes of the adrenal glands dramatically cast a shadow over the whole body. Hence the interest of researchers in elucidating the reaction of the adrenal glands when exposed to ionizing radiation and their role in the development of radiation sickness is clear. In addition, the similarity between many terminal manifestations owing to irradiation and after experimentally induced adrenal failure continues to attract attention. The data of most published works in which pathomorphologists cited the results of microscopic studies of the adrenal glands of animals exposed to generic irradiation are contradictory.
Keywords: ionizing radiation, adrenal gland, hormones, pathogenesis, morphogenesis.
РАДИАЦИОННО-ИНДУЦИРОВАННОЕ ПОРАЖЕНИЕ НАДПОЧЕЧНИКА
Шабдарбаева Д.М., Чайжунусова Н.Ж., Узбеков Д.Е., Аулейсова С.К., Русланова Б., Узбекова С.Е., Апбасова М.М.
1НАО «МУС», Семей, Казахстан
Как свидетельстуют литературные источники, надпочечники являются жизненно важными органами, участвующими своими гормонами в разнообразных обменных процессах. Следует отметить, что структурно-функциональное изменение железы резко сказывается на состоянии всего организма. Отсюда понятен интерес исследователей к выяснению реакции надпочечников при воздействии на организм ионизирующей радиации и их роли в развитии лучевой болезни. Кроме того, до сих пор продолжает обращать на себя внимание сходство между многими пострадиационными терминальными симптомами и экспериментально -индуцированной недостаточности надпочечников. Данные большинства опубликованных работ, в которых патоморфологи приводили результаты микроскопических исследований надпочечников животных, подвергнутых общему облучению, противоречивы.
Ключевые слова: ионизирующее излучение, надпочечник, гормоны, патогенез, морфогенез.
РАДИАЦИЯ ЭСЕР1НЕН БYЙРЕК YCTI БЕЗ ЗАЦЫМДАНУЛАРЫ
Шабдарбаева Д.М., Чайжунусова Н.Ж., Узбеков Д.Е., Эулейсова С.К., Русланова Б., Узбекова С.Е., Апбасова М.М.
«Семей медицина университет» коммерциялы; емес акционерлш когамы, Семей к;., ^азакстан
Буйрек уст1 безi езшщ гормондары аркылы сан алуан метаболитпк реакцияларды жузеге асыратын eмiрлiк мацызды агзалардыц бiрi болып табылатыны эдеби деректерден мэлiм. Буйрек усп безшщ курылымдык-функциялык eзгерiстерi букш организм децгешнде айтарлыктай терю ыкпалымен сипатталатынын айтып eткенiмiз жен. Осыган орай, иондаушы радиация эсерше бездщ реакциясы мен оныц сэулелж ауру дамуындагы релш тYсiндiруге деген зерттеушшердщ кызыгушылыгы ай;ын екенш де айта кеткенiмiз абзал. Сондай-ак, кептеген пострадиациялы; терминальды белгiлер мен эксперименттен кешнп бYЙрек Yстi безi жеткiлiксiздiгi арасындагы уксастыгы кYнi бYгiнге дейiн галымдардыц назарын тугызады. Демек, патоморфологтардын усынган кептеген енбектерiндегi сэулеленуге ушыраган жануарлар бездерiнiн микроскопия жYзiндегi зерттеу нэтижелерi бiр-бiрiне кайшы екенi шYбэсiз.
ТYЙiндi сездер: иондаушы сэулелеу, бYЙрек Ydi безi, гормондар, патогенез, морфогенез.
Introduction
It is generally known that adrenal gland is vital organ involved with their hormones in a diversity of metabolic reactions; a change in their function in one direction or another dramatically affects the whole body [1]. Hence the concernment of researchers in elucidating the suprarenal respond owing to radiation exposure and their pivotal role in the development of radiation sickness is explicitly. Furthermore, the similarity between manifold terminal manifestation after irradiation and after experimentally induced adrenal failure has long attracted attentiveness [2].
Ionizing radiation is commonly known, leading detrimental factors affecting to the suprarenal gland. It has always been believed that high doses of radiation trigger excessive injury to the body, while low doses practically hitherto little-known. However, provided that the former is irrefutable, then the latter is not everything is so simple [3]. Nowadays a universal approach has been developed that allows calculations of absorbed doses during internal irradiation of micro- and macrobiostructures with electrons, P-particles and quantum radiation in a wide range of energies that almost completely covers the range of radionuclide radiation energies used in experimental and clinical nuclear medicine. Unultimately, in this regard, contemporary radiobiologists actively continue to study individualized accumulated doses of radiation in the adrenal glands [4].
Unhesitatingly, that adrenal gland was chosen as the facility of our research, because stress such as radiation exposure is able to activate the hypothalamus-pituitary-adrenal system. On the one hand, the neuroendocrine system plays a leading role in coordinating the body's adaptive responses to adverse environmental factors, and on the other hand, its components themselves are exposed to adverse consequent [5]. Morphological study of the adrenal glands under the low dose radiation exposure will allow us to link structural reactive changes, to assess the functional reserves of this immunocompetency organ. In turn, this will allow us to justify the pathogenetically directed prevention of radiation-induced shifts in the body as a whole and in the adrenal glands in particular [6].
Objective of the study
Making distinctions between the nature of structural and biochemical changes in the adrenal glands at different types and doses of radiation exposure, as well as logical justification of the significance of the sophisticated issue concerning ionizing radiation exposure to the suprarenal glands.
Materials and methods
To achieve this goal, primarily, we have conducted a search and analysis of scientific publications. All accepted papers were indexed in the databases PubMed, Medline, cyberleninka, e-library, and Cochrane using the scientific search engine "Google Scholar". Before starting the search, the following search filters were displayed: experimental studies performed on mice and rats over the past 20 years (from 2000 to 2020), published in English, Japanese and Russian, as well as full versions of articles with clearly formulated and statistically proven conclusions. The following elements were included in the key points of search queries for forming a literature review: «ionizing radiation», «adrenal gland», «hormones», «»pathogenesis», «morphogenesis».
The criteria for excluding publications in the review were report summaries, newspaper publications, and personal messages. A total of 547 literary sources were found, from which 50 papers were selected for further analysis. After the end of the automatic search stage, we have performed a manual search for publications allowing to further identify the scientific sources included in our presented review.
Results and discussion
It is commonly known that in the first hours or days after irradiation in a wide range of doses, namely from 0,25 to 50 Gy, increased secretion of the adrenal glands is observed. It is no exaggeration to mention that the cortical hypersecretion is one of the mechanisms of mediated vascular changes and blood-forming organs [2]. Numerous pathologists maintain that mass of the adrenal glands, the size of both cortical and medullar zones change, the content of lipoid substances decreases. In irradiated adrenal glands, an increase of acid phosphatase activity, proteolytic enzymes and the development of destructive changes are noted [7]. Apparently, the consequential effect of radiation, in particular, from the nervous system, pituitary gland plays the predominant role in the adrenal cortex due to irradiation. Thus, in early period of radiation injury, functional activity of the adrenal glands increases, and in the subsequent periods depletion of the cortical and medullar substances and the development of atrophic processes occur [8].
From scientific experiment known that adrenalectomized mice and rats have been shown to be more sensitive to ionizing radiation effects that, eventually, prompted researchers to focus on elucidating the nature of changes in the cortical activity when exposed to ionizing radiation [9]. A decrease in the adrenal gland of rat cholesterol and ascorbic acid was observed several hours after
irradiation. In scientists opinion this above mentioned indicated an increase in adrenal cortex activity
[10]. The authors determined the content of some cortical hormones in the blood of the adrenal vein of rabbits at various times after irradiation and concluded that inhibition of adrenal cortex activity was not observed even later after irradiation. Based on the change in the ratio of the studied hormones, they firmly believe that there is a restructuring of the pattern of secretion by the adrenal cortex in the first 3 days after irradiation. Published data indicate an acceleration of the cortical activity due to irradiation
[11].
As a result of the conducted researches by pathologists, it was found that irradiation of animals caused noticeable structural changes of the glomerular, fascicular and reticular zones. It is worth noting that the glandular cortical substantion owing to irradiation is not undoubtedly delineated; within the zone, the cell strands lost their characteristic location [9,12]. At present a tremendous deterioration in the organ vascularization drew attention to itself. It is necessary to emphasize that microvessels were narrowed, the vascular lumen in the glomerular and fascicular zones was almost not visualized, and in such usually hyperemic zones as the reticular were much narrower [13]. Other results of morphological analysis of the adrenal cortex and alteration in hormone levels demonstrated that low-intensity ionizing radiation results in stimulation of glucocorticoid activity in different rodent species. Since the scientific work, numerous studies have shown that one of crucial regulators involved in the implementation of the general adaptation syndrome in various forms of stress are glucocorticoid hormones [14]. There is a perception that ionizing radiation induces a stress effect in a wide range of doses. With regard to low dose ionizing radiation, it is firmly believed that the stressful nature of the reaction is mainly due to the duration of exposure and the lack of full adaptation to it [15]. The unidirectional nature of changes in the adrenal glands, revealed in animals in natural conditions and in the experiment in response to low-intensity ionizing radiation, convincingly shows that adrenal cortical hyperactivity as a universal non-specific reaction, is the general mechanism of the system response to chronic low dose radiation. Since glucocorticoids have a powerful antioxidant activity, such the adrenal gland reaction can be aimed at preventing excessive processes of intracellular oxidation that develop under long-term low-intensity irradiation [8,16]. Along with the phenomena of high activity, the adrenal cortex had morphological signs of damage to tissue structures. Considerable importance should be given to presence of diffuse foci of the inflammatory response, namely leukocyte infiltrates and local necrotic process in the fascicular zone blurring of boundaries between zones, cortical disorganization with the appearance of local destruction and parenchymal atrophy. The most pronounced signs of microadenoma were observed against the background of increased functional activity of the organ, and there were various morphological disorders of the adrenal cortex [17].
According to scientists point of view, we would like to emphasize that alteration was almost found on other layers of the adrenal glands. For instance, the glomerular zone is not clearly separated from the fascicular zone. Moreover, cells with signs of hydropic degeneration: the cytoplasm is transparent, vacuolated [18]. Additionally, the nuclei are darker, the chromatin pattern is smoothed, and some nuclei demonstrate signs of pyknosis. Simultaneously, manifold cells contain functionally active nuclei are transparent with dispersed chromatin, pronounced marginal layer and nucleoli. It is necessary to point out that karyometric differences were found in the size of the nuclei [19].
The reticular zone cytoarchitectonics is impaired likewise, and microcirculatory vessels bed are very poorly developed as compared to intact ones. Noteworthy is the noticeable infiltration of the reticular zone by cells of lymphocytic, histiocytic, and fibroblastic origin. On the background of enhanced stromal pattern cortically be larger with oxyphilic, vacuolated cytoplasm. The range of fluctuations in their sizes is also much wider [20]. The nuclei are well structured: euchromatin, nucleolus, marginal chromatin layer. Some studies illustrates that lipofuscin influx was detected in the reticular zone. These above mentioned changes, such as an increase in the relative mass and volume of the adrenal glands, the fascicular zone hypertrophy, and an enlargement in the size of cells and nuclei of this above mentioned zone, are also discussed in other studies [21]. A tremendous increase in the thickness of the adrenal cortex bundle zone was found owing to epithelial cells hypertrophy.
Scientists demonstrate similar results: glomerular zone cells were spherical contained lipid droplets in the cytoplasm, whereas the fascicular zone cells were arranged in bundles. Numerous mitochondria in spherical shape and few lipid droplets were filled in the cytoplasm [22]. The reticular zone cells were polygonal. Fewer mitochondria and lipid droplets were observed in the cytoplasm than those in the other two area cells. Some of the secretory cells in the glomerular layer were degranulated or were atypical in the size, additionally mild connective tissues existed [23]. Manifold necrotic cells existing in the interstitium showed cytoplasmic vacuolation. Some cells in the glomerular zone arranged irregularly and protruded into the fascicular layer. Numerous lipid drops existed inside the cells. The necrotic cells and severe interstitial fibrosis were found in this above mentioned area. Other abnormal cells of a different type were arranged irregularly and loosely in the glomerular zone. These cells exhibited pale cytoplasm in comparing to the surrounding normal tissues. Most of these above mentioned cells are characterized by pyknotic nuclei [24,25]. Some hyperplastic cells were diminished as compared to the surrounding normal cells. Cytoplasmic vacuolation and interstitial fibrosis were observed. It is worth noting that unexpressed morphological changes in the hyperplasia free area of anterior lobe of the adrenal gland were observed at late period after irradiation. The vacuolation and degranulation in the cytoplasm were frequently observed in the adrenal medulla under the radiation effect by 20 Gy [26].
The morphological pattern of the adrenal medulla at irradiated patients also differs from the intact indistinctness, smoothness of cell contours, unexpressed differences in norepinephrocytes, additionally loss of the characteristic glomerular-vascular arrangement of cells. The spread of nuclei in size is much larger than in the intact group [27]. Because of the poor vascularization of the many cells do not have direct contact with the capillaries, which indirectly indicates a decrease in functional activity. At the border with the reticular zone of the cortex, there is moderate infiltration by cells of the histiolymphocytic series [28].
To prevent such organ lession we first need to understand the pathophysiology and immuno-biochemistry of these processes. It is well established that the hypothalamus-pituitary-adrenal axis is activated after radiation exposure and that this response is biphasic. It has been proposed that the first phase is considered as a «reflex response» of the organism and the later phase as the establishment of the manifest illness phase [29]. In studies of pathologists they have shown that irradiation of the heads of rats induced an enhancement of plasma corticosterone and adrenocorticotropic hormone levels with no variation in corticotropin-releasing factor labeling of the paraventricular nucleus early period after irradiation. The origin of the enhancement of these two parameters could be explained by a neuroendocrine reflex that goes through the hypothalamus [30]. Scientists have pointed out that although the corticotropin-releasing factor neuron is actively releasing secretogogue into hypophysial portal blood as indicated by elevated plasma adrenocorticotropic hormone concentrations, there is no measurable increase in the corticotropin-releasing factor primary transcripts in the paraventricular nucleus [31]. However, the temporal organization and functional interactions between these components are currently poorly defined in corticotropin-releasing factor neuroendocrine neurons. And their data showed that radiation-induced corticotropin-releasing factor release and subsequent gene activation possess distinct and separate thresholds, suggesting some degree of mechanistic dissociation [32].
On the other hand, some scientists suggested some peripheral action of ionizing radiation, through the release of inflammatory mediators, in the initiation of this early response rather than a direct detrimental effect of radiation on the adrenal glands [33]. This hypothesis is plausible because several studies have demonstrated the potent action of cytokines directly on the hypothalamus-pituitaryadrenal axis at different levels: the pituitary for the release of adrenocorticotropic hormone and the hypothalamus for the induction of expression and release of corticotropin-releasing factor. Moreover, clinical tests of pituitary-adrenal function include IL6 injections [34]. It was also suggested that circulating this above mentioned mediator may mediate the effects on the hypothalamus-pituitary-adrenal axis of locally increased levels of IL1 after an intramuscular injection of turpentine inducing a biphasic activation of the hypothalamus-pituitary-adrenal axis. This hypothesis was sustained by the absence of a systemic increase in IL1 after such a treatment although high circulating levels of IL6 in plasma were observed. Similarly, in mice we have previously shown increased plasma levels of Il6 and corticosterone after 8 Gy. These
increased levels were concomitant with elevated whole brain IL1 concentrations. However, Illb was not detected in the plasma. Scientists result could suggest a direct action of ionizing radiation or cytokines such as IL6 on the pituitary since IL6 can act directly on the pituitary to stimulate аdrenocorticotropic hormone secretion, which activates glucocorticoid release by a direct action on the adrenal glands [35].
The second phase that is considered as the «manifest illness phase», is characterized by gastroparesis and diarrhea. The decrease in the labeling of corticotropin-releasing factor neurons in the parvocellular region of the hypothalamus of rats on the 3rd days after total-body and abdominal gamma-irradiation with 10 Gy, the major pathophysiological feature in the understanding this processes [36]. This characterizes the negative feedback mechanism of glucocorticoid induced by both plasma corticosterone and аdrenocorticotropic hormone increase, probably as a result of direct effect of ionizing radiation on the pituitary and adrenals of irradiated rats observed decreased corticotropin-releasing factor mRNA levels at increased corticosterone concentrations. The molecular mechanisms by which glucocorticoid controls corticotropin-releasing factor receptor expression remains to be elucidated. Regulation of corticotropin-releasing factor receptor expression in vivo is complex and may involve the direct effects of glucocorticoid at the transcriptional and post-transcriptional levels and interaction with other regulatory factors, which are also under the control of glucocorticoid. But the exact regulatory mechanisms that control the hypothalamus-pituitary-adrenal axis after radiation exposure require further elucidation [37].
The authors conducted microscopic studies of the adrenal glands of irradiated pigs indicate a two-phase reaction of the adrenal cortex to the effects of ionizing radiation. In the first phase, in addition to the presence of foci of degenerative processes in the inner layers of the cortex, there is an increase in growth processes in the glomerular zone of the cortex, an increase in its thickness, as well as the number of cell nuclei. In the second phase, microscopic pattern illustrates a further increase in degenerative processes in the inner layers of the cortex, the appearance and increase in the number of sharply altered cell forms and pyknotic wrinkled nuclei in the glomerular zone, and the suppression of growth processes in it [38]. The data of most published works in which the authors cited the results of microscopic studies of the adrenal glands of animals exposed to general X-ray irradiation are contradictory [39]. Some authors found changes in the adrenal cortex, indicating an increase in its activity; others, on the contrary, speak of a decrease in the activity of the adrenal cortex. Refraining from a detailed consideration and discussion of these works, we think that the difference in the data of individual authors can be explained by the fact that they relate to different terms after irradiation [40]. Changes in the adrenal cortex activity are one of the general reaction manifestations of the body to radiation. These alterations are induced by reflex mechanisms, the chain of which also includes the anterior pituitary gland, whose adrenocorticotropic hormone is considered the main, if not the only, etiological agent of the adrenal cortex. As a regard of changes in the activity of the adrenal cortex, observed when exposed to X-rays on the body, cannot be explained only by changes in the content of аdrenocorticotropic hormone in the body [41]. This is especially true for the second phase which characterized by slow downing in the adrenal cortex activity at a later date after irradiation. It is necessary to allow the participation of other mechanisms leading ultimately to such changes in the adrenal cortex that even such a strong pathogen, like аdrenocorticotropic hormone, no longer acts on it. Scientists on the basis of morphological changes in the adrenal cortex, indicating an increase in growth processes in the glomerular zone on the first days after irradiation [42]. This question requires experimental clarification, especially since the involvement of growth hormone in the adrenal cortex is indicated in the literature sources. The authors indicate that administration of growth hormone to rats prevents the development of the adrenal cortex atrophy, which is usually observed with the cortisone administration. Scientists with the introduction of growth hormone to rats observed an increase in mitosis in the adrenal cortex, especially in the glomerular zone [43]. Nevertheless, even it is proved that in addition to аdrenocorticotropic hormone, other hormones of the anterior pituitary gland, in particular growth hormone are causative agents of the adrenal cortex, it is still theoretically unbearable to consider the anterior pituitary gland as the sole mediator in the implementation of reflex effects on the adrenal cortex [29].
Experiments with irradiation of guinea pigs in which the adrenal glands were previously denervated give reason to consider the presence of a reflex effect on the adrenal cortex, in addition to the intervention of the anterior pituitary gland. Nonetheless, in view of the generally disagreement about the secretory innervation of the adrenal cortex, the ambiguity of adrenaline role in the secretion of cortical hormones, experimental data require special consideration and a detailed discussion of what will be done later [44]. The relevant literature addresses the issue of the adrenal glands radiosensitivity, the possibility of direct exposure to X-rays on them under general exposure. This opinion is based on experimental data with shielding the area of the adrenal glands under general or local exposure to this area. Thus, shielding the area of the adrenal glands with a lead plate in rats or placing the adrenal glands in a lead capsule under general exposure reduced the mortality of rats compared to the mortality of animals irradiated with unprotected adrenal glands. The authors elaborate this result by eliminating the direct effect of X-rays on the adrenal glands [32]. In local low doses exposure of the back areas corresponding to the adrenal glands location, an increase in the weight of the adrenal glands, an increase in blood sugar, and an increase in nitrogen in the urine were found. The authors consider the results obtained as outcome of direct irritation of the adrenal cortex by X-rays. Similar data occur with the introduction of adrenocorticotropic hormone or cortisone. It appeared to numerous scientists that it is hardly possible to discuss the direct effect of ionizing radiation on the adrenal glands under general exposure to the body [45]. Rather, it could be assumed that the body surface corresponding to the adrenal glands area is the most susceptible reflex zone for the adrenal glands. From this point of view, the difference in the reaction to the general irradiation of the body of shielded and unshielded adrenal glands would be easier to go into detail [25]. In all these above mentioned cases, the calf muscle performance in pigs with shielded and unshielded adrenal glands was within the same limits. Therefore, in experiments we did not find a special effect of screening of the adrenal gland area on the change regarding activity of their cortex under general irradiation of the animal. An increase in the activity of the adrenal cortex in the first days after irradiation, apparently, should be considered as one of the manifestations of the body protective reaction. This is supported by the data of some researchers who showed that in the first 3-5 days after irradiation, animals apparently need an increased content of cortical hormones [46].
Studying the effect of adrenal gland removal on the survival of irradiated rats, the researchers found that the shorter the interval between irradiation and subsequent adrenal gland removal, the faster these rats die, whence they conclude that the need for increased hormones of the adrenal cortex in the body is greatest immediately after irradiation and decreases gradually by the fifth day after exposure [18]. Clarification of the causes of these changes and the determination of the possibilities for their prevention should be the first priority of the next study. In relation to the reaction to ionizing radiation of the second pillar of the medullar layer is almost no data. There are separate attempts to approach this issue by determining the adrenaline level in the blood after irradiation, but the results of these studies are very uncertain [22].
From the results of various studies of pathologists, we can conclude that adrenal hypertrophy due to increased secretion of adrenocorticotropic hormone is a classic type of organ response to stress [17]. Radiobiologists have, likewise, studied changes at the enzymatic level. According to finding that succinate dehydrogenase activity in adrenal homogenates of 5-month experimental groups tended to increase. It should be noted that there were no significant changes in the adrenal homogenates of 5-month-old rats from the side of the cyclooxygenase activity. When studying the diene conjugates level in adrenal homogenates of 5-month-old animals, it should be noted that the indicator of lipoperoxidation products had a tendency to elevation [47].
A certain representation of the contribution of direct and indirect changes can be obtained in model experiments with the effect of ionizing radiation on substrates and energy exchange enzymes. A decrease in the coefficient of oxidative phosphorylation in mitochondria of lymphoid organs is associated with a deep inhibition of phosphorylation reactions while inhibiting respiration, whereas in suprarenal tissue mitochondria is inextricably linked to activation of substrate oxidation [30]. Due to barrier permeability substances from the blood pass into the tissue fluid, and from the tissues into the blood, thus providing humoral connection and mutual availability of enzymes and biosubstrates as well
as maintaining trophic tissue structures. The separation of oxidative phosphorylation processes occurs as a result of enzyme number releasing from mitochondrial structures. Deterioration of intracellular mechanisms regulation can be not only a consequence, however also an important link in the initial mechanisms of radiation injury. It is essential to note that other respond that contributes to ATP synthesis in the body are vulnerable to radiation [41]. It is worth noting that radiation effect is accompanied by significant lipoperoxidation activation. It was found that ionizing radiation leads to an increase of free radicals level in the suprarenal tissue. It is generally known that finally, this above mentioned mechanism inextricably connected to high content of phospholipids. The experiment obtained convincing data that radiation-induced adrenal cells injury in combination with progressive obliterating vasculitis provoke adrenal gland necrosis. It should be noted that radiation damage to cells is caused by ROS-dependent oxidative stress entails DNA damage and inflammation in the adrenal glands. The inflammatory process occurs continuously through factors related to tissue repair. It is known that an increase in the content of lipoperoxidation products in the early stages is typical for tissues with high proliferative and metabolic activity. Eventually, the initiation, progression and chronization of radiation-induced adrenal gland injury may be due to molecular mechanisms and metabolic disorders [48].
For many decades, clinicians and practitioners have focused on various aspects of the effects of neutron radiation on the morphofunctional state of the adrenal glands. Summarizing the literature data, it can be stated that one of radiation detrimental effects is profound changes in the adrenal glands structure that can lead to the development of immune disturbance [11]. At lethal doses adrenal cortex stimulation is observed then normalization, later a second wave of increase is observed. The second phase of an increase in the corticosteroids level in the blood is the pituitary-adrenal respond to the developing endocrine pathology. Another reason for the increase in corticosteroid levels is the inability of the affected liver to inactivate them [28].
As far as cortical hormones are concerned that great importance in the body participating in various metabolic reactions. It is possible that majority of the shifts of the various sides of the exchange described in the corresponding literature under the radiation effect will partly find an elaboration for changes in the adrenal gland activity [14]. The symptoms of radiation sickness, namely muscular adynamia and hypotension are probably explained by the latter. The importance for the development of hypotension of a decrease in the adrenal medulla activity, its inability to produce adrenaline follows from the results on the adrenaline role in the blood pressure regulation [39]. Clinicians are increasingly starting to consider the relationship between radiation sickness and adrenal gland changes. We refer to one of the latest reviews of the clinic of chronic radiation sickness, where it is said about the third stage of this pathology: acute weakness, adynamia, severe and persistent hypotension develop. The patient's condition at this stage of the disease resembles a pattern of severe adrenal insufficiency [26].
To sum up, with a single exposure to the body of external radiation, a two-phase change in the adrenal cortex activity was detected: an increase in the first 2-3 days and a sharp decrease starting from the seventh day after irradiation. The cortical activity changes cannot be explained by variation in the content of adrenocorticotropic hormone [30]. Irradiation of animals with shielding of the adrenal gland area did not reveal a special significance of this region in the cortical activity change under generic irradiation. With a general exposure to the body, a sharp decline in the medullar activity was found starting from the seventh day after irradiation. The observations described by us allow us to express thoughts on the significance of the detected changes in the suprarenal activity in the development of radiation sickness [21].
Conclusion
The literature data obtained by us confirm the radiation role in the formation of histomorphological features characteristic of radiation-induced suprarenal injury, depending on both the dose and the type of radiation. According to the results of most of the leading studies in the field of radiology, the assessment of the effect of internal radiation on the adrenal glands has not yet been fully studied. Thus, the results of the literature review show that for radiobiologists and morphologists, it is undoubtedly relevant to continue research on the study of radiation effects on the hypothalamus-hypaphyseal-adrenal system. Since 56Mn became one of the dominant neutron-activated P-emitters during the first hours after the atomic bomb explosion in Hiroshima and Nagasaki [48], it is particular interest to study and compare the extent of structural and
functional changes in the immunocompetency organ, namely adrenal gland of individuals exposed to internal radiation, which will reveal informative criteria for evaluating the radiation effect depending on the accumulated dose [49]. The obtained data concerning both P- and y-rays effect to the suprarenal tissue can also contribute to the development of diagnostic criteria for assessing the influence of the radiation factor [50].
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Корреспонденция авторы: Шабдарбаева Дария Муратовна - «Семей медицина университет» коммерцияльщ емес акционерлш когамы, Патологиялык анатомия жэне соттык медицина кафедрасыньщ менгерушiсi, м.г.д., Семей, Кдзакстан; е-mail: dariya_kz@bk.ru
