Mitochondrial dysfunction in aging rat brain regions upon chlorpyrifos toxicity and cold stress: an interactive study

Mitochondrial dysfunction and consequent energy depletion are the major causes of oxidative stress resulting to bring alterations in the ionic homeostasis causing loss of cellular integrity. Our previous studies have shown the age-associated interactive effects in rat central nervous system (CNS) upon co-exposure to chlorpyrifos (CPF) and cold stress leading to macromolecular oxidative damage. The present study elucidates a possible mechanism by which CPF and cold stress interaction cause(s) mitochondrial dysfunction in an age-related manner. In this study, the activity levels of Krebs cycle enzymes and electron transport chain (ETC) protein complexes were assessed in the isolated fraction of mitochondria. CPF and cold stress (15 and 20 °C) exposure either individually or in combination decreased the activity level of Krebs cycle enzymes and ETC protein complexes in discrete regions of rat CNS. The findings confirm that cold stress produces significant synergistic effect in CPF intoxicated aging rats. The synergism between CPF and cold stress at 15 °C caused a higher depletion of respiratory enzymes in comparison with CPF and cold stress alone and together at 20 °C indicating the extent of deleterious functional alterations in discrete regions of brain and spinal cord (SC) which may result in neurodegeneration and loss in neuronal metabolic control. Hence, co-exposure of CPF and cold stress is more dangerous than exposure of either alone. Among the discrete regions studied, the cerebellum and medulla oblongata appears to be the most susceptible regions when compared to cortex and SC. Furthermore, the study reveals a gradual decrease in sensitivity to CPF toxicity as the rat matures.