Baicalein attenuates methamphetamine-induced loss of dopamine transporter in mouse striatum.
Methamphetamine (METH) has been shown to cause dopaminergic neurotoxicity. By using the loss of dopamine transporter (DAT) as a marker of neurotoxicity, this study was aimed to investigate the neuroprotective effect of baicalein against METH-induced striatal damages in mice. Results from Western blotting showed that repeated METH administration (5 mg/kg, i.p., four injections at 2-h interval) caused 40% decrease of DAT level in mouse striatum measured at 72h after the last injection. Despite of the ineffectiveness at high dose (3.0 mg/kg, i.p.), pretreatment with lower doses of baicalein (0.3-1.0 mg/kg, i.p.) significantly attenuated the METH-induced striatal DAT loss in a dose-dependent manner. Furthermore, baicalein diminished METH-induced increase in striatal malondialdehyde content and myeloperoxidase activity, markers for lipid peroxidation and neutrophil increase, respectively. In addition, the present study also revealed that baicalein effectively diminished the ROS production by leukocytes stimulated with METH or PMA, a phorbol ester used as a positive control of stimulant. Surprisingly, we found that METH-induced nNOS overexpression was further increased by the pretreatment with baicalein while the level of nNOS was not altered significantly by baicalein treatment alone. These results suggested that baicalein may attenuate methamphetamine-induced DAT loss by inhibiting the neutrophil increase and the lipid peroxidation caused by neutrophil-derived reactive oxygen species in striatum.
Wu
Ping-Ho
PH
Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC.
Shen
Yuh-Chiang
YC
Wang
Yea-Hwey
YH
Chi
Chin-Wen
CW
Yen
Jiin-Cherng
JC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D044950:Flavanones / Q000494:pharmacology*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D044950:Flavanones; D017382:Reactive Oxygen Species; D008694:Methamphetamine; C006680:baicalein; D008315:Malondialdehyde; D009195:Peroxidase; D052248:Nitric Oxide Synthase Type I