Influence of ezetimibe on ADMA-DDAH-NO pathway in rat liver subjected to partial ischemia followed by global reperfusion
PBN-AR
Instytucja
Wydział Lekarski (Uniwersytet Medyczny im. Piastów Śląskich we Wrocławiu)
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Pharmacological Reports
ISSN
1734-1140
EISSN
Wydawca
Elsevier Sp. z o.o.
DOI
Rok publikacji
2013
Numer zeszytu
1
Strony od-do
122-133
Numer tomu
65
Liczba arkuszy
Słowa kluczowe
en
ezetimibe
liver
ischemia/reperfusion
eNOS
ADMA
rat
Streszczenia
Język
en
Treść
Background We evaluated effect of ezetimibe on selected parameters determining NO level in rat liver subjected to ischemiareperfusion (IR). Methods Rats received ezetimibe (5 mg/kg) (groups E0 and EIR) or saline solution (groups C0 and CIR) intragastrically for 21 days. Then, the livers of CIR and EIR underwent ischemia (60 min) and reperfusion (4 h). Blood samples were obtained before surgery to estimate activities of aminotransferases, and just before ischemia and during reperfusion to estimate asymmetric and symmetric dimethylarginine (ADMA, SDMA) and arginine (Arg) levels. After IR, dimethylarginine dimethylaminohydrolase (DDAH) activity and endothelial nitric oxide synthase (eNOS) protein concentration were measured in liver homogenates.DDAHand protein arginine methyltransferase (PRMT) mRNA were quantified by real-time PCR in liver tissue samples. Results In CIR, the ADMA level was significantly higher compared to all other groups in 30 min and to E0 group in 120 min of reperfusion. In EIR, ADMAwas low, compared to non-ischemic groups. At 30 and 120 min of reperfusion, in non-ischemic groups the level of Arg and Arg/ADMAratio were significantly higher than in ischemic groups and E0 was the group with the highest levels of those parameters of all. In CIR, eNOS protein concentration was significantly lower than in ezetimibe-treated groups. Activity of DDAH was significantly higher in E0 than in non-treated groups. In ischemic groups, DDAH mRNA expression was significantly higher than in non-ischemic ones and PRMT mRNA expression was significantly higher in C0 than in all other groups. Conclusions Influence of ezetimibe on ADMA/DDAH/NO pathway demonstrated in this work may suggest protective properties of this drug on rat livers injured by IR and, to a lower extent, on livers non-subjected to IR.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
758621
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