Synergistic benefit of combined amlodipine plus atorvastatin on neuronal damage after stroke in Zucker metabolic rat.
Stroke is a major neurologic disorder and a leading cause of death in the world. We compared neuroprotective effects of single or combination therapy of amlodipine (AM) and atorvastatin (AT) in such a metabolic syndrome model Zucker rat after 90 min of transient middle cerebral artery occlusion (tMCAO). The animals were pretreated with vehicle, AM, AT, or the combination of AM plus AT for 28 days, and at 24h of tMCAO, infarct volume and immunohistochemical analyses were performed. The combination of AM plus AT treatment decreased the infarct volume stronger than each single treatment with AM or AT. The numbers of positive cells of oxidative stress markers such as 8-hydroxy-2'-deoxyguanosin (8-OHdG), 4-hydroxy-2-nonenal (4-HNE), and advanced end glycation products (AGE) and inflammation markers such as tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1(MCP-1) decreased dramatically in the combination-treated group compared with single AM- or AT-treated group. The present study showed that single AM or AT treatment showed neuroprotective effects both with antioxidative and anti-inflammatory mechanisms, but combination therapy of AM plus AT presented a further synergistic benefit in acute ischemic neural damages.
Department of Neurology, Graduate School of Medicine, Dentistry and pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558, Japan.
Hiromi
H
Kawai
Shoko
S
Deguchi
Kentaro
K
Deguchi
Toru
T
Yamashita
Yasuyuki
Y
Ohta
Jingwei
J
Shang
Fengfeng
F
Tian
Xuemei
X
Zhang
Ning
N
Liu
Wentao
W
Liu
Yoshio
Y
Ikeda
Tohru
T
Matsuura
Koji
K
Abe
D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000069059:Atorvastatin; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000473:pathology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D020521:Stroke / Q000473:pathology*
D000924:Anticholesteremic Agents; D002121:Calcium Channel Blockers; D006538:Heptanoic Acids; D011758:Pyrroles; D017311:Amlodipine; D000069059:Atorvastatin