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Acrylamide exposure increases oxidative stress and causes cytotoxicity. In order to understand the role of oxidative stress in acrylamide toxicity, we utilized Saccharomyces cerevisiae as a model organism grown in Yeast Peptone Dextrose (YPD) or Copper-Deficient Medium (CDM). Although the growth curves of yeast were comparable in these media, acrylamide treatment resulted in significant growth inhibition and colony formation only in the CDM. Copper-deficiency induced a decrease in the intracellular metallothionein levels, along with reduced Cu, Zn-SOD activity that appeared to increase the sensitivity of the yeast to the cytostatic effect of acrylamide. Increased dichlorofluorescein (DCF) fluorescence, enhanced formation of para-phenyl tertiary butyl nitrone (PBN)-hydroxyethyl adducts and a lowered reduced glutathione (GSH) content were observed under copper-deficient conditions, when challenged with acrylamide. The cytostatic effects and intracellular redox changes in response to acrylamide were ameliorated by antioxidant molecules viz. a viz. curcumin, β-carotene, vanillin and caffeic acid, which effectively decreased the oxidative stress and improved the growth recovery.

Copper-depleted cells are more sensitive to cisplatin-induced cytotoxicity due to upregulation of Ctr1, and enhanced accumulation of cis-diamminedichloroplatinum(II) (CDDP). Here we investigated the specific role of mitochondria in enhanced CDDP cytotoxicity under copper-depleted conditions. BY4741 Saccharomyces cerevisiae grown in yeast peptone and glycerol media were subjected to copper-sufficient or-deficient conditions. These cells were then treated with cisplatin to study the changes in cytochrome c oxidase activity, mitochondrial respiration, production of reactive oxygen species, cytosolic pH, translocation of cytochrome c from mitochondria to cytosol and mitochondrial membrane potential. Copper deprivation resulted in decreased cytochrome c oxidase activity and impaired respiration, which were further augmented by cisplatin. Cisplatin caused the release of mitochondrial cytochrome c and a dramatic drop in the mitochondrial membrane potential (ψ m). Also, cisplatin reduced the intracellular cytosolic pH in the copper-deficient cells. Copper-deficiency induced decrease in cytochrome c oxidase activity alters mitochondrial respiration which is further worsened by cisplatin, resulting in enhanced apoptosis.