Astrocyte activation: a key step in rotenone induced cytotoxicity and DNA damage
Authors: Ramesh Mathur
Supriya Swarnkar
Poonam Goswami
Ishan K Patro
Chandishwar Nath
Sarika Singh
Journal: Neurochemical research (2012)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Astrocytes; Rotenone; C6 cells; Cell survival; Free radicals
Affiliations: Division of Toxicology, CSIR-Central Drug Research Institute, P.O. Box 173, Lucknow, 226001 UP, India.

Abstract:  Astrocytes are the most abundant glial cells, which provide metabolic support for neurons. Rotenone is a botanical pesticide of natural origin, known to exhibit neurotoxic potential via inhibition of mitochondrial complex-I. This study was carried out to explore the effect of rotenone on C6 cells. The cell line C6 derived from rat glioma cells represents astrocyte-like cell. C6 cells were treated with rotenone (0.1, 1 and 10 μM) for 4 h. The effect of rotenone was studied on cell survival (MTT reduction and PI uptake); free radicals (ROS and RNS) and DNA damage (comet assay and Hoechst staining). The glial cell activation and apoptotic cell death was evaluated by expression of Glial fibrillary acidic protein (GFAP) and caspase-3 respectively. The treatment with rotenone resulted in decreased cell survival and increased free radical generation. Altered nuclear morphology and DNA damage were evident following rotenone treatment in Hoechst staining and Comet assay. Rotenone elevated expression of GFAP and caspase-3 that indicates glial cell activation and apoptosis, respectively. We further studied the effect of melatonin, an antioxidant, on the observed toxic effects. Co-incubation of antioxidant, melatonin (300 μM), significantly suppressed rotenone induced above-mentioned effects in C6 cells. Inhibitory effects of melatonin suggest that free radicals play a major role in rotenone induced astrocyte activation and cellular toxicity leading to apoptosis of astroglial cells. 

Retracted: No

PubPeer comments:
 The method presented in this paper (**Z. Xu** and M. Xia) was not very convincing (or at least not applicable) as pointed out by H. Liao, **Z. Xu**, X. Zeng in a paper (doi: 10.1016 j.knosys.2015.02.020) ![file] ![file] , 
 Firstly, these two papers defined the correlation coefficients from different perspectives and they both made contribution for the development of hesitant fuzzy theory. Secondly, the diagnoses can be clearly distinguished by using Table 4 and can also be clearly distinguished by using Figure 3, if we use a coordinate system with vertical axes that range from 0.95 to 1. Thirdly, the difference between the correlation coefficients proposed by Liao et al and the one proposed by Xu and Xia is the range, the ones given by Liao et al. range from -1 to 1, and the ones given by Xu and Xia range from 0 to 1. , 
 #2 Dear Prof. Xia, Thanks for your comment. This paper is authored by Z.S. Xu and M. Xia. The paper (doi: 10.1016 j.knosys.2015.02.020) is authored by H. Liao, Z. Xu, X. Zeng. The both paper share a common author Z.S. Xu. It is the authors of the paper (doi: 10.1016 j.knosys.2015.02.020) who claimed that the method in this paper is not convincing. If you do not agree on this claim, you may leave your comment publicly on https: pubpeer.com publications 76A42FBD89FCA187C1D876ED99848F ,