Altered level of apurinic/apyrimidinic endonuclease/redox factor-1 (APE/REF-1) mRNA in the hippocampus of ovariectomized rats treated by raloxifene against kainic acid.
1. Accumulated clinical evidence suggests that selective oestrogen receptor modulators (SERM), such as raloxifene, may be neuroprotective. Oxidative stress is a likely molecular mechanism in the neurotoxicity of kainic acid (KA), an excitotoxic substance. The expression levels of the apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1) gene seem to correlate with cellular sensitivity to reactive oxygen species (ROS) and a reduction in the expression of APE/Ref-1 may cause oxidative DNA damage. 2. The aim of the present study was to assess the effects of KA and raloxifene on the level of APE/Ref-1 mRNA in the hippocampus of ovariectomized rats. The expression of the APE/Ref-1 gene was quantified using reverse transcription followed by real-time polymerase chain reaction. 3. The results show that the level of APE/Ref-1 mRNA increased significantly in raloxifene-treated rats. However, raloxifene treatment did not affect the seizure severity induced by KA. We also observed that raloxifene treatment against simultaneous KA injection maintained the increased level of APE/Ref-1 mRNA in the hippocampus. 4. Therefore, the results of the present study seem to support previous data suggesting the potential significance of raloxifene in neuroprotection.
Yalcin
Ayfer
A
Department of Biochemistry, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey. yalcina@pharm.ege.edu.tr
Kanit
Lutfiye
L
Durmaz
Guliz
G
Sargin
Sehnaz
S
Terek
Cosan H
CH
Tanyolac
Bahattin
B
D000818:Animals; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D007608:Kainic Acid / Q000037:antagonists & inhibitors*; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D051381:Rats; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*
D012333:RNA, Messenger; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D007608:Kainic Acid