No abstract

Terpinolene induces apoptotic cell death via oxidative stress and mitochondrial impairment.

Camphor induces oxidative stress-mediated apoptotic cell death.

Alpha-thujone, widely used in beverages (1–5 mg/kg), is known to have cytotoxic effects, but the mode of action and the role of potential apoptotic proteins in yeast cell death should be unraveled. In this study, we used Schizosaccharomyces pombe, which is a promising unicellular model organism in mechanistic toxicology and cell biology, to investigate the involvement of pro-apoptotic factors in alpha-thujone-induced cell death. We showed alpha-thujone-induced ROS accumulation-dependent cytotoxicity and apoptosis. In addition, we used superoxide dismutase-deficient cells (sod1 and sod2 mutants) to understand the effect of oxidative stress. Alpha-thujone caused significant cytotoxicity and apoptotic cell death, particularly in sod mutants. Moreover, two potential apoptotic factors, pca1 and pnu1 (pombe caspase-1 and pombe nuc1) were investigated to understand which factor mediates alpha-thujone-induced cell death. Pca1-deficient cells showed increased survival rates and reduced apoptosis in comparison to parental cells after chemical treatment while pnu1 mutation did not cause any significant change and the response was found identical as of parental cells. Yeast responded to alpha-thujone in caspase-dependent manner which was very similar to that for acetic acid. In conclusion, alfa-thujone-induced apoptosis and accounting mechanisms, which were mediated by ROS and driven by Pca1, were clarified in the unicellular model, S. pombe.

Di-n-butyl phthalate (DBP) widely used plasticizer in the plastic industry, affects regulation of the endocrine system and causes toxicity in animals. In the present study, the aim was to study the toxic effects/damages of DBP exposure using Hsp70 levels and histopathological changes in Carp liver and gill. Hsp70 expression levels were assessed as specific biomarker of in vivo ecotoxicological stress. Carp (Cyprinus carpio) were exposed to sub-lethal concentration of DBP (di-n-butyl phthalate, 1 mg/L) for 4, 24 and 96 h. Gill and liver tissues were evaluated histopathologically and RNA quantifications for Hsp70 expression levels were carried out using a two-step real-time RT-PCR. In liver, a rapid but non-significant increase in mRNA levels in the first 4 h was observed. mRNA levels significantly increased up to 2-3 fold after 24 and 96 h (p < 0.05). However, irregular mRNA level changes were also recorded: Gill specific and time-dependent regulation of Hsp70 expression were 4-5 fold inhibition after 4 and 24 h (p < 0.05), then increased up to 4 fold after 96 h (p < 0.05). Histopathological findings support altered transcription results as: Epithelial lifting, hyperplasia, fusion of secondary lamellae, telangiectasis, passive hyperemia and hydropic degeneration. Significant alterations of Hsp70 levels were likely due to a tissue specific response against chemical stress, cellular damage and lesions due to DBP. Carp was found to be a suitable experimental model for toxicology, and Hsp70 mRNA levels are reliable, specific biomarkers.