Lipoic acid inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after pilocarpine-induced seizures.
Alpha-lipoic acid has some neuroprotective properties, but this action has not been investigated in models of epilepsy. The aim of the present study was to investigate the protective efficacy of α-lipoic acid (lipoic acid) against pilocarpine-induced cell death through the caspase-dependent or -independent mitochondrial apoptotic pathways. Wistar rats were injected intraperitoneally with 0.9% saline (control group), pilocarpine (400 mg/kg, pilocarpine group) alone, or α-lipoic acid (20 mg/kg) in association with pilocarpine (400 mg/kg) 30 min before administration of α-lipoic acid. After the treatments all groups were observed for 24 h. Cell death was reduced in lipoic acid-treated rats. Cytosolic translocation of cytochrome c and subsequent activation of caspase-3 were reduced by lipoic acid treatment. AIF nuclear translocation and subsequent large-scale DNA fragmentation were also decreased in lipoic acid-treated rats. Our study suggests that lipoic acid inhibits both caspase-dependent and -independent apoptotic pathways and may be neuroprotective against hippocampal damage during pilocarpine-induced seizures.
Laboratory of Research in Experimental Neurochemistry of Federal University of Piaui, Piaui, Brazil.
Pauline Sousa
PS
dos Santos
Chistiane Mendes
CM
Feitosa
Gláucio Barros
GB
Saldanha
Adriana da Rocha
Ada R
Tomé
Dejiang
D
Feng
Rivelilson Mendes
RM
de Freitas
D000818:Animals; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010862:Pilocarpine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008063:Thioctic Acid / Q000494:pharmacology*
D018696:Neuroprotective Agents; D010862:Pilocarpine; D008063:Thioctic Acid; D020169:Caspases