Title
Protektivni efekat blokatora kalcijumovih kanala na intoksikaciju aluminijumom - eksperimentalni model
Creator
Bojanić, Novica, 1984-
CONOR:
75673865
Copyright date
2021
Object Links
Select license
Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)
License description
Dozvoljavate samo preuzimanje i distribuciju dela, ako/dok se pravilno naznačava ime autora, bez ikakvih promena dela i bez prava komercijalnog korišćenja dela. Ova licenca je najstroža CC licenca. Osnovni opis Licence: http://creativecommons.org/licenses/by-nc-nd/3.0/rs/deed.sr_LATN. Sadržaj ugovora u celini: http://creativecommons.org/licenses/by-nc-nd/3.0/rs/legalcode.sr-Latn
Language
Serbian
Cobiss-ID
Theses Type
Doktorska disertacija
description
Datum odbrane: 26.11.2021.
Other responsibilities
predsednik komisije
Đinđić, Boris
član komisije
Milojković, Maja
član komisije
Živančević Simonović, Snežana
član komisije
Čolović, Nataša
Academic Expertise
Medicinske nauke
University
Univerzitet u Nišu
Faculty
Medicinski fakultet
Group
Katedra za fiziologiju
Alternative title
Protective effect of calcium channel blocker on aluminium induced intoxication - an experimental model
Publisher
[N. Z. Bojanić]
Format
131 list
description
Bibliografija: listovi 101-124.
description
Pathophysiology
Abstract (en)
Introduction. Aluminum is a non-essential element, the third most abundant in the Earth's crust. Since the second half of the twentieth century, the use and exposure of the living world to the toxic effects of bioavailable aluminum has been progressively increasing. We are exposed to aluminum through water, food, pharmaceutical and cosmetic products, as well as through air pollution. The results of modern research link aluminum intoxication with the occurrence of anemia, osteoporosis, encephalopathy and a number of neurodegenerative diseases (Alzheimer's disease, parkinsonism, autism), reproductive toxicity, respiratory diseases (asthma, chronic bronchitis), immune disorders and breast cancer. Aluminum is used as an adjuvant in vaccines, because it strengthens the immune response. At the time of the emergence of new viruses and the strengthening of the anti-vaccine movement and the fear that aluminum from vaccines is responsible for the increase in autism, it is very important to find a way to reduce its accumulation and toxic effects. The pathogenetic mechanisms of the toxic action of aluminum are insufficiently elucidated. The results of clinical and experimental studies indicate that there are several pathogenetic mechanisms by which Al exhibits toxic effects on cells: oxidative stress, disruption of membrane function, alteration or inhibition of enzyme function, and disruption of intracellular signaling. It has been found that aluminum ions can modify various signaling pathways and functions of secondary messengers, which are involved in essential processes such as cell growth, differentiation and apoptosis.
The objectives of the study were based on the hypothesis that the disturbance of calcium homeostasis regulation represents a strong pathogenetic mechanism in the development of aluminum toxicity and that blocking its channels can mitigate and/or eliminate the effect of chronic exposure to aluminum. The aim was:
- to elucidate the mechanism of toxic action of aluminum through the effect on calcium channels and determine the possible protective effect of pretreatment by blocking calcium channels with verapamil,
- to examine the influence of chronic administration of aluminum and premedication with verapamil on changes in hematological and biochemical parameters
- to assess the deposition of aluminum in the liver, testis and kidney tissues and the possible protective effect of verapamil
- to examine the influence of chronic exposure to different doses of aluminum trichloride and premedication with verapamil on testicular morphology.
- to examine the effect of chronic exposure to different doses of
aluminum trichloride and premedication with verapamil on liver morphology and function.
- to examine the degree of apoptosis after chronic administration of aluminum and premedication with verapamil in testicular and liver tissues using proteins of the Bcl-2 family.
Material and methods: 36 male Sprague Dawley rats were included in the experiment, which were divided into 6 groups and were treated as follows: control (K) with saline, V with verapamil, E1 with 10 mg and E2 with 20 mg AlCl3. Sixty minutes after premedication with verapamil, E3 received 10 mg and E4 20 mg AlCl3. After 8 weeks, the animals were sacrificed and blood was taken for analysis of hematological and biochemical parameters and tissues for both pathohistological and aluminum content examinations.
Results. The results of hematological tests are presented (counts of erythrocytes, leukocytes, thrombocytes, relative and absolute leukocyte counts, hemoglobin concentrations, hematocrit, MCV, MCH, MCHC, iron, ferritin, transferrin, hepcidin, UIBC, TIBC, TSAT activity; aminotransferase, alanine aminotransferase, alkaline phosphatase, amylase, lactate dehydrogenase, creatine kinase and gamma-glutamyl transferase; CRP concentration; aluminum concentration in liver, testis and kidney tissues; pathohistological findings in liver and testis tissues; testicular morphometry and immunohistochemical cytoplasmic expression of Bax, Bid, and BCL-2 in liver and testicular tissues.
Discussion: the results are explained and discussed. The pathogenetic aspects of hematological and biochemical changes caused by aluminum intoxication and the protective effects of premedication with verapamil are discussed, as well as on the accumulation of aluminum in the liver and testicular tissue The analysis of the pathogenetic aspect of the toxic effect of aluminum through the influence on calcium homeostasis is given and the latest literature data are discussed in comparison.
Conclusion: it has been proven that chronic application of aluminum leads to significant changes in hematological and biochemical parameters with a pronounced dose-dependent character; The changes in biochemical and hematological parameters (microcytic-hypochromic anemia, leukocytosis, thrombocytosis and elevated values of hepcidin and ferritin) have shown a statistically significant improvement with verapamil premedication. Significant deposition of aluminum in the liver, kidney and testicular tissue was proven, as well as that premedication with verapamil led to a statistically significant reduction in the deposition of aluminum in the mentioned tissues. Immunohistochemical staining has showed a high expression of proapoptotic markers Bax and Bid, which is the most pronounced in testicular tissue, and a high degree of apoptosis expressed by proapoptotic markers Bax and Bid in young germ epithelial cells, but also in Leydig cells. These changes have shown to be mitigated in cases of premedication with verapamil and that the possible protective effect of pharmacological blockade of calcium channels by verapamil is indicated.
Authors Key words
Hronična intoksikacija aluminijumom, blokada voltažno zavisnih kalcijumovih kanala, verapamil, apoptoza, morfometrija
Authors Key words
Chronic intoxication with aluminum, blockade of voltage-gated calcium channels, verapamil, apoptosis, morphometry
Classification
616-092:[546.62:615.9(043.3)
Subject
B 530
Type
Tekst
Abstract (en)
Introduction. Aluminum is a non-essential element, the third most abundant in the Earth's crust. Since the second half of the twentieth century, the use and exposure of the living world to the toxic effects of bioavailable aluminum has been progressively increasing. We are exposed to aluminum through water, food, pharmaceutical and cosmetic products, as well as through air pollution. The results of modern research link aluminum intoxication with the occurrence of anemia, osteoporosis, encephalopathy and a number of neurodegenerative diseases (Alzheimer's disease, parkinsonism, autism), reproductive toxicity, respiratory diseases (asthma, chronic bronchitis), immune disorders and breast cancer. Aluminum is used as an adjuvant in vaccines, because it strengthens the immune response. At the time of the emergence of new viruses and the strengthening of the anti-vaccine movement and the fear that aluminum from vaccines is responsible for the increase in autism, it is very important to find a way to reduce its accumulation and toxic effects. The pathogenetic mechanisms of the toxic action of aluminum are insufficiently elucidated. The results of clinical and experimental studies indicate that there are several pathogenetic mechanisms by which Al exhibits toxic effects on cells: oxidative stress, disruption of membrane function, alteration or inhibition of enzyme function, and disruption of intracellular signaling. It has been found that aluminum ions can modify various signaling pathways and functions of secondary messengers, which are involved in essential processes such as cell growth, differentiation and apoptosis.
The objectives of the study were based on the hypothesis that the disturbance of calcium homeostasis regulation represents a strong pathogenetic mechanism in the development of aluminum toxicity and that blocking its channels can mitigate and/or eliminate the effect of chronic exposure to aluminum. The aim was:
- to elucidate the mechanism of toxic action of aluminum through the effect on calcium channels and determine the possible protective effect of pretreatment by blocking calcium channels with verapamil,
- to examine the influence of chronic administration of aluminum and premedication with verapamil on changes in hematological and biochemical parameters
- to assess the deposition of aluminum in the liver, testis and kidney tissues and the possible protective effect of verapamil
- to examine the influence of chronic exposure to different doses of aluminum trichloride and premedication with verapamil on testicular morphology.
- to examine the effect of chronic exposure to different doses of
aluminum trichloride and premedication with verapamil on liver morphology and function.
- to examine the degree of apoptosis after chronic administration of aluminum and premedication with verapamil in testicular and liver tissues using proteins of the Bcl-2 family.
Material and methods: 36 male Sprague Dawley rats were included in the experiment, which were divided into 6 groups and were treated as follows: control (K) with saline, V with verapamil, E1 with 10 mg and E2 with 20 mg AlCl3. Sixty minutes after premedication with verapamil, E3 received 10 mg and E4 20 mg AlCl3. After 8 weeks, the animals were sacrificed and blood was taken for analysis of hematological and biochemical parameters and tissues for both pathohistological and aluminum content examinations.
Results. The results of hematological tests are presented (counts of erythrocytes, leukocytes, thrombocytes, relative and absolute leukocyte counts, hemoglobin concentrations, hematocrit, MCV, MCH, MCHC, iron, ferritin, transferrin, hepcidin, UIBC, TIBC, TSAT activity; aminotransferase, alanine aminotransferase, alkaline phosphatase, amylase, lactate dehydrogenase, creatine kinase and gamma-glutamyl transferase; CRP concentration; aluminum concentration in liver, testis and kidney tissues; pathohistological findings in liver and testis tissues; testicular morphometry and immunohistochemical cytoplasmic expression of Bax, Bid, and BCL-2 in liver and testicular tissues.
Discussion: the results are explained and discussed. The pathogenetic aspects of hematological and biochemical changes caused by aluminum intoxication and the protective effects of premedication with verapamil are discussed, as well as on the accumulation of aluminum in the liver and testicular tissue The analysis of the pathogenetic aspect of the toxic effect of aluminum through the influence on calcium homeostasis is given and the latest literature data are discussed in comparison.
Conclusion: it has been proven that chronic application of aluminum leads to significant changes in hematological and biochemical parameters with a pronounced dose-dependent character; The changes in biochemical and hematological parameters (microcytic-hypochromic anemia, leukocytosis, thrombocytosis and elevated values of hepcidin and ferritin) have shown a statistically significant improvement with verapamil premedication. Significant deposition of aluminum in the liver, kidney and testicular tissue was proven, as well as that premedication with verapamil led to a statistically significant reduction in the deposition of aluminum in the mentioned tissues. Immunohistochemical staining has showed a high expression of proapoptotic markers Bax and Bid, which is the most pronounced in testicular tissue, and a high degree of apoptosis expressed by proapoptotic markers Bax and Bid in young germ epithelial cells, but also in Leydig cells. These changes have shown to be mitigated in cases of premedication with verapamil and that the possible protective effect of pharmacological blockade of calcium channels by verapamil is indicated.
“Data exchange” service offers individual users metadata transfer in several different formats. Citation formats are offered for transfers in texts as for the transfer into internet pages. Citation formats include permanent links that guarantee access to cited sources. For use are commonly structured metadata schemes : Dublin Core xml and ETUB-MS xml, local adaptation of international ETD-MS scheme intended for use in academic documents.