Indicators of apoptosis in mitochondria of liver cells in female С57ВL/6 mice with B16/F10 melanoma growing in presence of chronic neurogenic pain

Abstract

Background. The liver is one of the richest organs in terms of the number and density of mitochondria; it is also a critical site for many metabolic pathways. The aim of the study was to analyze indicators of apoptosis in liver mitochondria in female C57ВL/6 mice with B16/F10 melanoma growing alone and in presence of chronic neurogenic pain. Methods. Female C57ВL/6 mice (n=168) were studied. Animals were divided into groups: intact group (n=21); controls (n=21) with a model of chronic neurogenic pain (CNP) created by bilateral sciatic nerve ligation; comparison group (n=63) with subcutaneous transplantation of B16/F10 melanoma; main group (CNP+B16/F10) (n=63) with subcutaneous transplantation of B16/F10 melanoma 3 wks after modeling CNP. Cytochrome C (ng/g protein), caspase-9 (ng/g protein), Bcl-2 (ng/g protein), AIF (ng/g protein), and calcium (Ca2⁺) (mmol/g protein) were measured by ELISA in the liver mitochondrial fraction. Results. After 1 wk of melanoma growth, AIF increased by 2.2 times, cytochrome C increased by 1.7 times (p<0.05), and caspase-9 decreased by 2.0 times compared to the intact group values. After 3 wks, calcium decreased by 4.7 times, AIF by 7.1 times, cytochrome C by 1.7 times (p<0.05), and caspase-9 increased by 1.6 times (p<0.05). After 1 wk, tumor development in the presence of CNP was accompanied by decreases in AIF by 29.3 times and cytochrome C by 2.0 times, compared to control CNP values. After 3 wks of melanoma growth in presence of CNP, AIF decreased by 6.6 times, cytochrome C by 4.7 times, and calcium by 32.8 times. Caspase-9, on the contrary, increased by 1.5 times (p<0.05). Conclusions. The presence of CNP comorbidity during the tumor development facilitates earlier occurrence of disorders in the electron transport chain of hepatocyte mitochondria.