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Biomed Pharmacother ; 155: 113805, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36271578

RESUMEN

BACKGROUND: Although the beneficial role of adipose-derived mesenchymal stem cells (AD-MSCs) in acute liver injury has been addressed by numerous studies employing different liver injury inducers, the role of rat AD-MSCs (rAD-MSCs) in diclofenac sodium (DIC) - induced acute liver injury has not yet been clarified. OBJECTIVE: This study aimed to investigate whether rat adipose- rAD-MSCs injected intraperitoneal could restore the DIC-induced hepatoxicity. METHODS: Hepatotoxicity was induced by DIC in a dose-based manner, after which intraperitoneal injection of rAD-MSCs was performed. RESULTS: Here, the transplanted cells migrated to the injured liver, and this was evidenced by detecting the specific SRY in the liver samples. After administering DIC, a significant decrease in body weight, survival rate, serum proteins, antioxidants, anti-apoptotic gene expression, and certain growth factors, whereas hepatic-specific markers, pro-inflammatory mediators, and oxidative, pro-apoptotic, and ER-stress markers were elevated. These adverse effects were significantly recovered after engraftment with rAD-MSCs. This was evidenced by enhanced survival and body weight, improved globulin and albumin values, increased expression of SOD, GPx, BCL-2, VEGF, and FGF-basic expression, and decreased serum ALT, AST, ALP, and total bilirubin. rAD-MSCs also reduced liver cell damage by suppressing the expression of MDA, IL-1B, IL-6, BAX, JNK, GRP78/BiP, CHOP, XBP-1, and cleaved caspase 3/7. Degenerative hepatic changes and multifocal areas of fatty change within liver cells were observed in DIC-received groups. These changes were improved with the transplantation of rAD-MSCs. CONCLUSIONS: We could conclude that targeted AD-MSCs could be applied to reduce hepatic toxicity caused by NSAIDs (DIC).


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Ratas , Femenino , Animales , Caspasa 3/metabolismo , Diclofenaco/toxicidad , Diclofenaco/metabolismo , Interleucina-6/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Células Madre Mesenquimatosas/metabolismo , Hígado/metabolismo , Mediadores de Inflamación/metabolismo , Superóxido Dismutasa/metabolismo , Antiinflamatorios no Esteroideos/toxicidad , Antiinflamatorios no Esteroideos/metabolismo , Bilirrubina/metabolismo , Antiinflamatorios/metabolismo , Albúminas , Peso Corporal
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