Chronic Pretreatment with AcetylEmphasis Type="S

Authors: G Nagesh Babu Alok Kumar Ram Lakhan Singh

Publish Date: 2010/03/09

Volume: 19, Issue: 2, Pages: 319-329

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Abstract

Cellular oxidative stress and energy failure were shown to be involved in Glutamate lGlu neurotoxicity whereas acetyllcarnitine ALCAR and ±DLαlipoic acid LA are known to be key players in the mitochondrial energy production To evaluate the effects of the above antioxidants adult rats were pretreated with ALCAR 100 mg/kg ip for 21 days and both ALCAR and LA 100 mg/kg ip + 50 mg/kg ip for 21 days before stereotactically administering lGlu bolus 1μmole/1 μl in the cerebral cortex Results showed that acute lGlu increased ROS P  0001 LPO P  0001 Ca2+ P  0001 TNFα P  0001 IFNγ P  0001 NO P  0001 levels and mRNA expression of Caspase3 Casapase9 iNOS and nNOS genes with respect to salineinjected control group Key antioxidant parameters such as SOD CAT GSH GR along with mitochondrial transmembrane potential Ψ∆m were decreased P  005 while ALCAR pretreatment prevented these effects by significantly inhibiting ROS P  0001 LPO P  0001 Ca2+ P  005 TNFα P  005 IFNγ P  0001 NO P  001 levels and expression of the above genes This chronic pretreatment of ALCAR also increased SOD CAT GSH GR and Ψ∆m P  0001 P  0001 P  005 P  005 and P  0001 respectively with respect to lGlu group The addition of LA to ALCAR resulted in further increases in CAT P  005 GSH P  001 GR P  005 Ψ∆m P  005 and additional decreases in ROS P  0001 LPO P  005 Ca2+ P  005 TNFα P  005 and mRNA expression of iNOS and nNOS genes with respect to ALCAR group Hence this “onetwo punch” of ALCAR + LA may help in ameliorating the deleterious cellular events that occur after lGlu

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