title: Kaurane diterpenes as mitochondrial alterations preventive agents under experimental oxidative stress conditions.
abstract: BACKGROUND
  Foliol, linearol, and sidol are the most common diterpenes found in Sideritis L. spp. (Lamiaceae) with a wide range of demonstrated properties including anti-inflammatory, antioxidant, and anti-apoptotic effects.
  
  
  OBJECTIVE
  For the first time, the present work was studied for the potential protective role of these kaurane-type diterpenes on mitochondrial oxidative stress induced by H2O2 in the human astrocytoma U373-MG cell line and in the rat adrenal pheochromocytoma PC12 cell line.
  
  
  METHODS
  Mitochondrial protection was assayed at 5 and 10 µM concentrations for 24 h (for kaurane diterpenes) and H2O2 as oxidative stress inducer (0.1 mM for PC12 cells and 1 mM for U373-MG, for 30 min). ATP concentration was determined by high-performance liquid chromatography (HPLC), and changes in mitochondrial membrane potential, caspase-3 activity as well as in cytosolic and mitochondrial calcium levels were assessed by fluorometric techniques, by using specific fluorescent probes.
  
  
  RESULTS
  Pretreatments for 24 h with linearol and sidol, prior to H2O2 exposure, acted as mitochondrial alterations preventive agents by increasing membrane potential (over 40-60% in PC12 cells and over 10-20% in U373-MG), restoring both cytosolic and mitochondrial calcium homeostasis (linearol at 10 µM caused a 3.5-fold decrease in cytosolic calcium concentration in PC12 cells), decreasing caspase-3 activity (over 1.25-1.5-fold for linearol and sidol) and avoiding ATP depletion (linearol increased over 20% ATP level in both cell types).
  
  
  CONCLUSIONS
  Our results suggest that linearol and sidol could provide protective activity by targeting mitochondria in response to the deleterious changes induced by H2O2.
authors.affiliation: a Department of Pharmacology , Faculty of Pharmacy, University Complutense , Madrid , Spain .
authors.forename: Elena
authors.initials: E
authors.lastname: González-Burgos
authors.affiliation: b Center for Neuroscience and Cell Biology, University of Coimbra , Coimbra , Portugal , and.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Duarte
authors.affiliation: a Department of Pharmacology , Faculty of Pharmacy, University Complutense , Madrid , Spain .
authors.forename: Maria Emilia
authors.initials: ME
authors.lastname: Carretero
authors.affiliation: b Center for Neuroscience and Cell Biology, University of Coimbra , Coimbra , Portugal , and.|c Faculty of Medicine , Laboratory of Physiology, University of Coimbra , Coimbra , Portugal.
authors.forename: Paula Isabel
authors.initials: PI
authors.lastname: Moreira
authors.affiliation: a Department of Pharmacology , Faculty of Pharmacy, University Complutense , Madrid , Spain .
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Gómez-Serranillos
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D045786:Diterpenes, Kaurane / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D031365:Sideritis
chemical_list: D000975:Antioxidants; D045786:Diterpenes, Kaurane; D010936:Plant Extracts; D006861:Hydrogen Peroxide
keywords: Hydrogen peroxide; mitochondria; natural products; reactive oxygen species