SHORT REPORT/RAPID COMMUNICATION PDGF-BB Protects Mitochondria from Rotenone in T98G Cells Ricardo Cabezas • Marcos Fidel Avila • Janneth Gonza ´lez • Ramon Santos El-Bacha ´ • George E. Barreto Received: 20 October 2014 / Revised: 27 November 2014 / Accepted: 8 December 2014 Ó Springer Science+Business Media New York 2014 Abstract Rotenone is one of the most-studied neurotoxic substances as it induces oxidative stress processes both in cellular and animal models. Rotenone affects ATP gener- ation, reactive oxygen species (ROS) production, and mitochondrial membrane potential in neurons and astro- cyte-like cells. Previous epidemiologic studies have sup- ported the role of neurotrophic factors such as BDNF and GDNF in neuroprotection mainly in neurons; however, only very few studies have focused on the importance of astrocytic protection in neurodegenerative models. In the present study, we assessed the neuroprotective effects of PDGF-BB against toxicity induced by rotenone in the astrocytic-like model of T98G human glioblastoma cell line. Our results demonstrated that pretreatment with PDGF-BB for 24 h increased cell viability, preserved nuclear morphology and mitochondrial membrane poten- tial following stimulation with rotenone, and reduced ROS production nearly to control conditions. These observations were accompanied by important morphological changes induced by rotenone and that PDGF-BB was able to pre- serve cellular morphology under this toxic stimuli. These findings indicated that PDGF-BB protects mitochondrial functions, and may serve as a potential therapeutic strategy in rotenone-induced oxidative damage in astrocytes. Keywords Rotenone Á PDGF-BB Á Mitochondria Á Reactive oxygen species Á Neuroprotection Introduction Rotenone is one of the most-studied neurotoxic substances used as a model for Parkinson disease (PD) and oxidative stress events in cellular and animal models (Betarbet et al. 2000; Greenamyre et al. 2003). This neurotoxin is a natu- rally occurring isoflavonoid produced in the leaves, roots, and rhizomes of tropical legumes from the genres Derris, Lonchocarpus, and Tephrosia. Rotenone serves as a high- affinity noncompetitive inhibitor of complex I, thus affecting ATP generation (Cabezas et al. 2012; Gyulkhandanyan et al. 2003). Previous epidemiological studies have supported the hypothesis that prolonged exposure to pesticides such as rotenone or paraquat is a risk factor for PD (Betarbet et al. 2000; Greenamyre et al. 2003; Tanner et al. 2011). For example, a recent case–control study from the NIH, which reviewed 110 PD cases and 358 controls, observed that PD incidence was increased 2.5 times in individuals while comparing the reported use of rotenone with nonusers (Tanner et al. 2011). Another study in agricultural workers from East Texas identified a significant increased risk (OR = 10.9) of PD with the continuous use of rotenone (Dhillon et al. 2008). Similarly, different groups have demonstrated that continuous systemic administration of rotenone to rats and mice reproduces key features of PD, including selective degeneration of the nigrostriatal dopa- minergic system, microglial activation, formation of cyto- plasmic inclusions in neurons, movement disorders, mitochondrial membrane potential lost, and mitochondrial damage (Betarbet et al. 2000; Greenamyre et al. 2003, 2010; Hoglinger et al. 2005; Ogawa et al. 2005). Electronic supplementary material The online version of this article (doi:10.1007/s12640-014-9509-5) contains supplementary material, which is available to authorized users. R. Cabezas Á M. F. Avila Á J. Gonza ´lez Á G. E. Barreto (&) Departamento de Nutricio ´n y Bioquı ´mica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogota ´, D.C., Colombia e-mail: gsampaio@javeriana.edu.co R. S. El-Bacha ´ Departamento de Biofunc ¸a ˜o, Universidade Federal da Bahia, Salvador, Bahia, Brazil 123 Neurotox Res DOI 10.1007/s12640-014-9509-5