Mbiri

Ezetimibe ndi choletsa champhamvu komanso chatsopano cha mayamwidwe a cholesterol [1].

Cholesterol ndi molekyulu ya lipid ndipo imafunika kuti ipange ndi kusunga nembanemba kukhulupirika ndi madzimadzi. Komanso, imagwira ntchito ngati kalambulabwalo wa vitamini D, bile acid ndi mahomoni a steroid.

M'maselo osiyanitsa a Caco-2 opangidwa ndi carotenoid (1 μM), ezetimibe (10 mg / L) amalepheretsa kayendedwe ka carotenoid ndi 50% yoletsa ɑ-carotene ndi β-carotene. Komanso, idalepheretsa kuyenda kwa β-cryptoxanthin, lycopene ndi lutein:zeaxanthin (1: 1). Nthawi yomweyo, ezetimibe adaletsa mayendedwe a cholesterol ndi 31%. Ezetimibe inachepetsa kufotokoza kwa zolandilira pamwamba SR-BI, ATP kumanga makaseti transporter, subfamily A (ABCA1), Niemann-Pick mtundu C1 Monga 1 mapuloteni (NPC1L1) ndi asidi retinoid receptor (RAR) γ, sterol-regulatory element kumanga mapuloteni SREBP -1 ndi SREBP-2, ndi chiwindi X cholandirira (LXR)β [3].

Mu apolipoprotein E knockout (apoE-/-) mbewa, ezetimibe (3 mg/kg) amaletsa mayamwidwe a cholesterol ndi 90%. Ezetimibe imachepetsa cholesterol ya m'magazi, imachulukitsa milingo ya HDL, ndikuletsa kukula kwa atherosulinosis [1]. M'mayesero a anthu a gawo lachitatu, Ezetimibe (10 mg) adachepetsa kwambiri LDL cholesterol, cholesterol yonse ndi triglycerides ndikuwonjezera mulingo wa HDL cholesterol [2].

Zolozera:
[1]. Davis HR Jr, Compton DS, Hoos L, et al. Ezetimibe, choletsa champhamvu cha cholesterol mayamwidwe, chimalepheretsa kukula kwa atherosulinosis mu apoE knockout mbewa. Arterioscler Thromb Vasc Biol, 2001, 21 (12): 2032-2038.
[2]. Clader JW. Kupezeka kwa ezetimibe: mawonekedwe kuchokera kunja kwa cholandirira. J Med Chem, 2004, 47(1): 1-9.
[3]. Panthawi ya A, Dawson HD, Harrison EH. Mayendedwe a carotenoid amachepa ndipo mafotokozedwe a lipid transporters SR-BI, NPC1L1, ndi ABCA1 amatsitsidwa m'maselo a Caco-2 omwe amathandizidwa ndi ezetimibe. J Nutr, 2005, 135(10): 2305-2312.

Kufotokozera

Ezetimibe (SCH 58235) ndi choletsa champhamvu cha cholesterol mayamwidwe. Ezetimibe ndi Niemann-Pick C1-like1 (NPC1L1) inhibitor, ndipo ndi activator yamphamvu ya Nrf2.

Mu Vitro

Ezetimibe (Eze) imagwira ntchito ngati choyambitsa champhamvu cha Nrf2 popanda kuyambitsa cytotoxicity. Ezetimibe imathandizira kusintha kwa Nrf2, monga kuwululidwa ndi luciferase reporter assay. Ezetimibe imayang'aniranso ma jini amtundu wa Nrf2, kuphatikiza GSTA1, heme oxygenase-1 (HO-1) ndi Nqo-1 mu Hepa1c1c7 ndi ma cell a MEF. Ezetimibe imayang'anira chibadwa cha Nrf2 mu maselo a Nrf2 +/+ MEF, pamene kulowetsedwa kumeneku kumatsekedwa kwathunthu mu maselo a Nrf2-/- MEF. Kuphatikizidwa pamodzi, Ezetimibe amachita ngati Nrf2 inducer m'njira yodziyimira payokha ya ROS[1]. Ma hepatocyte a huh7 aumunthu amapangidwa kale ndi Ezetimibe (10μM, 1 h) ndi kulowetsedwa ndi palmitic acid (PA, 0.5 mM, 24 h) kuti apangitse hepatic steatosis. Chithandizo cha Ezetimibe chimalepheretsa kwambiri kuchuluka kwa PA-kuwonjezeka kwa triglycerides (TG), zomwe zimagwirizana ndi kafukufuku wathu wa nyama. Chithandizo cha PA chinapangitsa kuchepa kwa pafupifupi 20% kwa mawu a mRNA a ATG5, ATG6, ndi ATG7, omwe adawonjezedwa ndi chithandizo cha Ezetimibe. Kuphatikiza apo, chithandizo cha Ezetimibe chinakulitsa kwambiri kuchepetsedwa kwa PA-kuchepetsa kuchuluka kwa mapuloteni a LC3 [2].

MCE sinatsimikizire paokha kulondola kwa njirazi. Iwo ndi ongotchula chabe.

Administration of Ezetimibe (Eze) amachepetsa kulemera kwa chiwindi cha mbewa zomwe zimadyetsedwa ndi zakudya za methionine- ndi choline-deficient (MCD). Izi zikugwirizana ndi zotsatira zopindulitsa za Ezetimibe pa hepatic steatosis. Histology ya chiwindi imawonetsa madontho angapo amafuta amtundu wambiri mu mbewa pazakudya za MCD, koma chithandizo cha Ezetimibe chimachepetsa kuchuluka ndi kukula kwa madonthowo. Kuphatikiza apo, hepatic fibrosis mu mbewa zomwe zimadyetsa zakudya za MCD zimachepetsedwa kwambiri ndi Ezetimibe[1]. Magazi ndi chiwindi cha lipids kuphatikizapo TG, mafuta aulere acids (FFA), ndi mafuta a cholesterol (TC) amachepa kwambiri mu makoswe a OLETF omwe amathandizidwa ndi Ezetimibe. Komanso, makoswe a OLETF amawonetsa kuchuluka kwa shuga m'magazi, insulin, HOMA-IR, TG, FFA, ndi TC kuposa nyama za LETF, zomwe zimachepetsedwa kwambiri ndi Ezetimibe. Kuphatikiza apo, kusanthula kwa histological kunawonetsa kuti makoswe owongolera OLETF adawonetsa madontho akulu a lipid mu hepatocyte kuposa zowongolera za LETO zofananira ndi zaka, zomwe zimachepetsedwa ndi kayendetsedwe ka Ezetimibe[2].

Kusungirako

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