BAPTA-AM Nanoparticle for the Curing of Acute Kidney Injury Induced by Ischemia/Reperfusion
| Autor: | Zhiyu He, Keqing Huang, Arvind Dhinakar, Qiaoli Yu, Jun Wu, Xinru You, Haoyu Tang, Yang Kang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Renal function Bioengineering Caspase 3 Apoptosis 02 engineering and technology Pharmacology urologic and male genital diseases Kidney Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Lactate dehydrogenase medicine Animals General Materials Science Egtazic Acid Creatinine biology Superoxide Dismutase Cytochrome c Acute kidney injury Acute Kidney Injury 021001 nanoscience & nanotechnology medicine.disease Rats 030104 developmental biology medicine.anatomical_structure chemistry Reperfusion Injury biology.protein Nanoparticles 0210 nano-technology Reperfusion injury |
| Zdroj: | Journal of biomedical nanotechnology. 14(5) |
| ISSN: | 1550-7033 |
| Popis: | Ischemia-reperfusion (I/R) is a major cause of acute kidney injury (AKI), which is associated with unacceptably high mortality rates in ICU. This research was designed to explore the therapeutic effect of BAPTA-AM (1,2-Bis(2-aminophenoxy) ethane-N,N,N,N-tetraacetic acid tetrakis(acetoxymethyl ester)) nanoparticle (BA-N) on AKI. BA-N was developed by liposome strategy and characterized by standard methods. The rat model was selected and the rats were randomly allocated into four groups: (1) Normal group; (2) Sham-operated group; (3) Model group (I/R + NS); (4) BA-N treatment group (I/R + BA-N). AKI model was established via clipping the bilateral renal artery with a microvascular clamp for 45 min. After reperfusion, serum cystatin C (Cys C), creatinine (Cr), blood urea nitrogen (BUN), lactate dehydrogenase (LDH) and caspase 3 levels were determined for the assessment of renal function. Kidney samples were then collected for the measurement of renal malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. The assays of histological examination, ELISA, immunohistochemistry, western blot, TUNEL and RT-PCR were utilized for the detection of apoptosis. The results demonstrated that AKI model caused a significant decreasing in SOD activity, accompanied by a remarkable increase in Cys C, Cr, BUN, LDH, MDA, caspase 3 and cytochrome c (Cyt C) level, compared to the control group. BA-N (100 μg/kg i.v.) significantly improved renal function and histopathological appearance, restored MDA level and SOD activity, decreased Bax/Bcl-2 ratio, caspase 3 activity, Cyt C release and TUNEL positive apoptotic cells. Our studies indicated that BA-N plays a renal-protective role, probably through antiapoptotic and antioxidant mechanisms. BA-N may regulate mitochondria pathway via decreasing Bax/Bcl-2 ratio, inhibiting caspase 3 expression and Cyt C release. Overall, BA-N may have potentials as an anti-AKI drug. |
| Databáze: | OpenAIRE |
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