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Variation of biochemical and molecular genetic parameters in rats exposed to carbon monoxide and carbon dioxide

2015
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Advisor: Prof. Dr. Osman Celbiş

Abstract (EN)

By providing objective criteria of the toxicological analysis and the conclusion which takes place mostly without any doubt demonstrates the importance of the analysis. For instance, cold-induced dead spots during an autopsy can be seen in a similar way of carbon monoxide poisoning and this is a situation encountered in forensic science practice. At the same time, if the carboxyhemoglobin (COHb) level from blood sample taken from a corpse which was burnt in an open area is not in lethal boundaries may lead to problems in diagnosis and differential diagnosis. Developing methods of analysis and using the devices that apply these methods in the field of forensic toxicology and using less materials to get clearer results will contribute the development toxicology and forensic medicine along with the technology. The genotoxicity reactions which can be measured by the development of Biochemical and Genetic Toxicology along with interdisciplinary approach provided by Forensic Toxicology will contribute the development of Forensic Science and enlightenment of criminal cases more effectively. In asphyxia caused by carbon monoxide, although using carboxyhemoglobin (CO-Hb) level, the resulting toxicity condition differs in each man. Besides, the severity of the case is not all the time correlated with the COHb level, therefore different mechanisms are thought to be involved in toxicity. In order to explain this situation the studies on more specific indicators than carboxyhemoglobin is increasing day by day. In the differentiation of asphyxia cases, some theories have been proposed as a classical information on the derivative of hemoglobin and myoglobin. Neuroglobin is a newly defined derivative of monomeric globin derivatives. Neuroglobin, which assumed to have neuroprotective role in neuroendocrine tissues from the conducted studies, was defined at the beginning of 2000s. The neuroglobin is reported to be a respiratory protein, which contains Hem- derivatives like hemoglobin and myoglobin, is found in human and vertebrates. In the studies stated that, the central nervous system (CNS) and Peripheral Nervous System (CSS) have the highest expression level, retina has a high level, however, the mainly it is synthesized in the brain. There are some opinions about some other organs like Anterior pituitary, adrenal gland, the testes and endocrine tissue which may synthesize it. Some studies on Neuroglobin synthesis because of the cases caused by the damage of brain and neurotoxic agents that result in cases such as arsenic were done. In this study, the change of parameters in blood and brain tissues of rat which were exposed to carbon monoxide and carbon dioxide, neuroglobin gene expression levels in brain tissues and the histopathological changes in brain tissues aimed to be determined. The hypothesis arose from the idea that neuroglobin synthesis will be in different amounts by the effects of carbon dioxide and carbon monoxide. According to the results of the study; the gases taken from the blood rats showed that pCO2 was high in carbon dioxide group and pHCO was high in carbon monoxide group when we compare them with the control group. The increase in oxidative stress was due to differences between pH ve HCO3 values. When we look at histopathological analysis, it was seen that neuronal damage in the carbon group was in more serious levels than the carbon monoxide group. The differences in asphyxia mechanisms because of carbon monoxide and carbon dioxide, could cause this situation. Globular affinity of carbon dioxide is lower than carbon monoxide and the easiness of reversible binding to oxygen may relatively explain why the exposure to carbon dioxide is less. In biochemical analysis, oxidant / antioxidant imbalance has been observed in both groups when compared to the control group and an increase in oxidant activity has also been seen. It is known that the increase in oxidant stress may lead to various metabolic disorders in organisms. The determination of the differences between two exposures confirm the literature. In the hypothesis of our genetic toxicology study, which was the first study in Turkey, we anticipated that there was changes related to neuroglobin mRNA level, however, statistically significant differences between groups during this time and dose was not observed. When the average of the groups considered, the average of the two groups appear to be higher than the control group. If the level of neuroglobin mRNA, synthesized in hypoxia and is mentioned to have neuroprotective effect, provided and the change of the exposure time and doses of the given gases are achieved, this study may get different results. Besides, it is known that an mRNA is not limited with only one protein synthesis, it could synthesize more than one or a different number of proteins depending on the environmental conditions. Therefore, we need to remember that the protein level of neuroglobin and neuroglobin mRNA's might be different from each other. We think that our study will be an example to experimental animal studies which involves genetic toxicology. In addition, we are proud to have pioneered to an undeveloped interdisciplinary approach in terms of forensic toxicology in our country. Keywords: Carbon monoxide poisoning, exposure to carbon dioxide, asphyxia, neuroglobin, CO-Hb

Author

Dr. Mustafa Doğan

How to Cite

Mustafa Doğan (Medical Specialty Thesis). Variation of biochemical and molecular genetic parameters in rats exposed to carbon monoxide and carbon dioxide, 2015, İnönü University.

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