Protective Effect of Taurine on Tri ortho cresyl Phosphate (TOCP)-Induced Cytotoxicity in C6 Glioma Cells - Advances in Experimental Medicine and Biology - page 221

22.4 Discussion

It has been known that TOCP exert neurotoxicity in humans and sensitive animal
species (Craig and Barth 1999 ; Zhang et al. 2007 ).Studies on the mechanism and
protection of TOCP neurotoxicity mainly focused on neurons. However, recent
research indicates that astrocytes are affected in, and contribute to, the neurotoxicity
of OPs. Zurich et al. ( 2004 ) reported that the neurotoxicity of two OPs, chlorpyrifos
and parathion, are involved in astrocytes. Guizzetti et al. ( 2005 ) also reported an
inhibitory effect on astrocyte proliferation using chlorpyrifos in vitro. In the present
study, we used C6 glioma cells pretreatment with taurine and then exposure to
TOCP to assess the protective effects of taurine on C6 glioma cells against TOCP-
induced injury. The experimental results demonstrated that when C6 glioma cells
are exposed to TOCP, there is a significant decrease in cell viability by MTT assay
and increase in LDH release. Pretreatment with taurine significantly increases cell
viability and decreases LDH release in a concentration-dependent manner. Our
results are consistent with the above studies also suggest that TOCP exerts toxic
effects on astrocyte and taurine has protective role against TOCP-induced injury.
To support the conclusion of TOCP cytotoxicity on the cultured astrocytes, the
morphology changes were observed by the inverted phase-contrast microscope.
When compared with the untreated astrocytes, the density of normal cells was con-
sciously decreased. C6 glioma cells displayed obvious cell body shrinkage, nuclear
condensation, and loss in cell membrane integrity. Taurine dramatically prevented
cell morphological deterioration in a concentration-dependent manner.
Oxidative stress is one of the major mechanisms of cell death in a variety of dis-
ease and injury (Floyd 1999 ; Love 1999 ; Qiao et al. 2005 ). It is characterized by an
imbalance between the intracellular productions of reactive oxygen species (ROS)
and the cellular defense mechanisms, which is an excess of ROS accompanied by a
reduced capability of the natural antioxidant systems. Astrocyte is prominent antioxidant
defense system in the brain and they have high concentrations of GSH and GPx
(Desagher et al. 1996 ; Dringen et al. 2000 ). It was reported that astrocyte GSH
system responds to many toxic substances in time- and concentration-dependent
manners. Zhang et al. ( 2007 ) reported that TOCP caused changes of lipid peroxida-
tion and antioxidative status in nerve tissues of hens. Garcia et al. ( 2001 ) reported
that chlorpyrifos enhanced reactive oxygen species (ROS) formation in C6 glioma
cells. In this study, we found that TOCP decreased the content of GSH and the activ-
ity GPx in C6 glioma cells (Fig. 22.4 ). This finding suggests that TOCP may disturb
astrocyte antioxidant system which leads to cell injury.
Taurine is an important molecule able to modulate glutamatergic signaling, pre-
venting excitotoxicity and oxidative stress (Junyent et al. 2011 ; Saransaari and Oja
2010 ). In particular, taurine exerts cytoprotective effects against various types of
brain injury (Gao et al. 2011 ; Ricci et al. 2009 ; Taranukhin et al. 2012 ) .In the current
study we also found that taurine has protection against TOCP-induced injury and
significantly prevented the depletion of GSH (Fig. 22.4a ) and preserved the activity
of GPx (Fig. 22.4b ).