In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e21557-e21557
Abstract:
e21557 Background: Mitochondrial dysfunction is one of the mechanisms for the development of heart disease that requires close study. Diabetic cardiomyopathy is the leading cause of death in such patients due to the development of heart failure. Chronic pain may be associated with higher prevalence of cardiovascular disease, and little is known about its potential biological consequences. The purpose of this study was to analyze parameters of free radical oxidation and mitochondrial respiration in heart cells in experimental animals with malignant tumors growing in presence of diabetes mellitus (DM) and chronic neurogenic pain. Methods: The study included outbred female rats (n = 32) weighing 180-220 g and C57BL/6 female mice (n = 84) weighing 21-22 g. Experimental groups of rats were: intact animals (n = 8), controls (n = 8) with DM, comparison group (n = 8) with subcutaneously inoculated Guerin’s carcinoma, and main group (n = 8) with Guerin’s carcinoma subcutaneously inoculated after 1 week of persistent hypothyroidism. Experimental groups of mice were: intact animals (n = 21), controls (n = 21) with a model of chronic neurogenic pain (CNP) created by bilateral sciatic nerve ligation, comparison group (n = 21) with subcutaneously inoculated melanoma (B16/F10), and main group (n = 21) with melanoma subcutaneously inoculated 3 weeks after the CNP model was created (CNP+B16/F10). Heart mitochondria were isolated by differential centrifugation. Levels of cytochrome C (ng/g of protein), 8-hydroxy-2'-deoxyguanosine (8-OHdG) (ng/g of protein), and malondialdehyde (MDA) (nM/g of protein) were measured in mitochondrial samples by ELISA. Statistical analysis was performed using the Statistica 10.0 program. Results: DM in rats upregulated 8-OHdG by 6.3 times and MDA by 1.9 times (p 〈 0.05) and downregulated cytochrome C by 1.5 times (p 〈 0.05) in heart cell mitochondria, compared to intact values. DM+Guerin’s carcinoma in rats increased 8-OHdG by 14.0 times and MDA by 1.7 times (p 〈 0.05) and decreased cytochrome C by 1.5 times (p 〈 0.05), compared to intact values. CNP in mice did not affect the studied parameters in mitochondria of the heart. CNP+B16/F10 in mice increased 8-OHdG by 7.1 times and MDA by 1.6 times (p 〈 0.05) and decreased cytochrome C by 1.6 times (p 〈 0.05) in heart cell mitochondria. Conclusions: Comorbidity (diabetes mellitus, chronic neurogenic pain) together with malignant pathology aggravates mitochondrial dysfunction of heart cells which results in DNA damage and destabilization of the respiratory chain mediated by free radical oxidation processes.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2022.40.16_suppl.e21557
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2022
detail.hit.zdb_id:
2005181-5
