Oxidative stress and mitochondrial impairment mediated apoptotic cell death induced by terpinolene in  Schizosaccharomyces pombe .
Terpinolene is one of the most abundant monoterpenes used as a food supplement or odorant in cosmetics and the pharmaceutical industry. In this study, we aimed to assess apoptotic, oxidative and cytotoxic effects of terpinolene. We used the fission yeast ( Schizosaccharomyces pombe ) as a promising uni-cellular model organism in molecular toxicology and cell death research, due to its resemblance to mammalian cells at the molecular level. After terpinolene exposure (200-800 mg L -1 ), the IC 50  and LC 50  were calculated as 349.17 mg L -1  and 593.87 mg L -1 . Cells, stained with acridine orange/ethidium bromide and DAPI, showed apoptotic nuclear morphology, chromatin condensation and fragmentation. 2,7-Dichlorodihydrofluorescein diacetate (DCFDA) fluorescence gradually increased (1.5-2-fold increase) in correlation with increasing concentrations of terpinolene (200-800 mg L -1 ). Mitochondrial impairment at higher concentrations of terpinolene (400-800 mg L -1 ) was shown by Rhodamine 123 staining. Real-time PCR experiments showed significant increases (1.5-3-fold) in SOD1 and GPx1 levels ( p  < 0.05) as well as 2-2.5-fold increases ( p  < 0.05) in pro-apoptotic factors, Pca1 and Sprad9. The potential effects of terpinolene on programmed cell death and the underlying mechanisms were clarified in unicellular model fungi,  Schizosaccharomyces pombe .
Agus HH, Sarp C, Cemiloglu M