Impact of gender and age on hyperthermia-induced changes in respiration of liver mitochondria

Abstract

Aim: This study aimed to compare hyperthermia-induced changes in respiration and generation of reactive oxygen species (ROS) in liver mitochondria derived from animals of different gender and age. Methods: The effects of hyperthermia (40–47◦C) on oxidation of different substrates and ROS production were estimated in mitochondria isolated from the liver of male and female rats of the 1–1.5, 3–4, or 6–7 months age. Results: Gender-dependent differences in response of respiration to hyperthermia were the highest at 3–4 months of age, less so at 6–7 months of age, and only minor at juvenile age. Mild hyperthermia (40–42◦C) stimulated pyruvate + malate oxidation in mitochondria of females, but inhibited in mitochondria of males in the 3–4 month age group. The resistance of mitochondrial membrane to hyperthermia was the highest at 3–4 month males, and the lowest in the 6–7 month age group. Inhibition of glutamate + malate oxidation by hyperthermia was caused by thermal inactivation of glutamate dehydrogenase. ROS generation at 37◦C was higher at 1–1.5 month of age, but the increase in ROS generation with rise in temperature in this age group was the smallest, and the strongest in 6–7 month old animals of both genders. Conclusions: The response to hyperthermia varies during the first 6–7 months of life of experimental animals: stronger gender dependence is characteristic at 3–4 months of age, while mitochondria from 6–7 months animals are less resistant to hyperthermia.