Vitamins E and C reduce oxidative stress and mitochondrial permeability transition caused by camptothecin – an in vitro study

Abstract

Camptothecin (CPT), a broad spectrum antineoplastic agent, is known to induce oxidative stress and mitochondria are among the main sources of intracellular reactive oxygen species (ROS). We investigated the merit of vitamins E and C supplementation on CPT-induced mitochondrial alterations in vitro. Following treatment of isolated liver mitochondria with CPT, we assessed the mitochondrial membrane permeability transition (MPT), concentration of malondialdehyde, antioxidants and activities of the enzymes of the respiratory chain and Krebs cycle. Our results provide evidence that CPT caused mitochondrial swelling, increased lipid peroxidation and transition of mitochondrial permeability. The CPT lowered the levels of reduced mitochondrial thiols suggesting that thiol oxidation is the mechanism underlying CPT-induced MPT. Identical experiments were also performed after preincubating the mitochondria with vitamins E and C. It was found that vitamins E and C pretreatment inhibited the deleterious effects of CPT and loss of enzyme activity was restored by antioxidant supplementation. Our results suggest that the toxicity of CPT was mediated by an increase in ROS production by mitochondria. However, the addition of vitamins E or C ameliorated the oxidative stress. We propose that an attempt to counteract the deleterious consequences of chemotherapy with nutritional therapies may be a rational approach in superior patient care especially in a disease like cancer.

Keywords:

• antioxidants
• cytochrome c oxidase
• lipid peroxides
• mitochondrial swelling
• reactive oxygen species