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Biochim Biophys Acta Mol Basis Dis ; 1866(12): 165911, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768679

RESUMO

Cisplatin is used as a chemotherapy drug in the treatment of various types of cancer. Mitochondrial dysfunction, oxidative stress and inflammation have been identified as major mechanisms of cisplatin nephrotoxicity. The present study investigated the protective effects of pure gallic acid and nanoparticle gallic acid nanoparticles (nano-gallic acid) on cisplatin induced nephrotoxicity. Nano-gallic acid was prepared by double emulsions-solvent evaporation technique using Eudragit RS 100 polymer and polyvinyl alcohol as carrier. Then, the physicochemical characterization of the nanoparticles was examined. In the present study, renal mitochondria were isolated using different centrifugal methods. Our data indicated that the doses of 50 and 100 mg/kg gallic acid and 10 mg/kg nano-gallic acid significantly decreased mitochondrial reactive oxygen species (ROS) formation, mitochondrial membrane damage (ΔΨm), mitochondrial malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and significantly increased mitochondrial glutathione (GSH), mitochondrial superoxide dismutase (MnSOD), mitochondrial glutathione peroxidase (GPX) and mitochondrial catalase compared to the cisplatin treated group. Histopathological studies also confirmed biochemical tests. Finally, our results confirmed that the pure gallic acid and its nanoparticle improved renal oxidative stress, inflammation and mitochondrial dysfunction in acute nephrotoxicity induced by cisplatin in rat. Nano-gallic acid (10 mg/kg) was selected as the most effective dose. The findings of this study showed the superiority of nano-gallic acid against pure gallic acid. In conclusion, nano-gallic acid-loaded Eudragit-RS 100 as a novel antioxidant can be considered in the treatment of renal complications of cisplatin.


Assuntos
Resinas Acrílicas/farmacologia , Ácido Gálico/farmacologia , Inflamação/prevenção & controle , Nefropatias/prevenção & controle , Mitocôndrias/efeitos dos fármacos , Nanopartículas/química , Substâncias Protetoras/farmacologia , Resinas Acrílicas/administração & dosagem , Administração Oral , Animais , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/antagonistas & inibidores , Relação Dose-Resposta a Droga , Ácido Gálico/administração & dosagem , Inflamação/induzido quimicamente , Inflamação/metabolismo , Injeções Intraperitoneais , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Masculino , Mitocôndrias/metabolismo , Nanopartículas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Ratos , Ratos Wistar
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