Antifibrotic Effect of Combination of Nilotinib and Stem Cell-Conditioned Media on CCl 4 -Induced Liver Fibrosis.

Autor: Shiha G; Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt.; Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Nabil A; Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt.; Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Egypt., Lotfy A; Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt.; Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Egypt., Soliman R; Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt.; Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt., Hassan AA; Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt., Ali IS; Delta University for Science and Technology, Egypt., Gad DF; Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Zahran F; Biochemistry Department, Faculty of Science, Zagazig University, Egypt.
Jazyk: angličtina
Zdroj: Stem cells international [Stem Cells Int] 2020 Feb 03; Vol. 2020, pp. 6574010. Date of Electronic Publication: 2020 Feb 03 (Print Publication: 2020).
DOI: 10.1155/2020/6574010
Abstrakt: Liver fibrosis is the excessive extracellular matrix accumulation of proteins, such as collagen, which follows the chronic liver diseases. Advanced liver fibrosis leads to cirrhosis and liver failure. Nilotinib is a second-generation tyrosine kinase inhibitor, which showed antifibrotic efficacy. Stem cell therapy still has some limitations such as oncogenesis, unexpected differentiation, and ethical consideration. Stem cells secrete cytokines and growth factors that showed paracrine-mediated antifibrotic and anti-inflammatory effects in vivo and in vitro. Thus, stem cell-conditioned medium (SC-CM), which contains the secretory proteins of stem cells, may have an antifibrotic role. This study was carried out to examine the antifibrotic effect of Nilotinib and stem cell exosomes on CCl 4 -induced liver fibrosis in rats. Male Wistar rats were injected intraperitoneally with CCl 4 twice a week for 9 weeks and given daily treatments of Nilotinib (20 mg/kg), stem cell exosomes (0.5 ml/rat), and the combination treatment of Nilotinib and stem cell exosomes during the last 5 weeks of CCl 4 intoxication. Liver fibrosis and also antifibrotic efficacy of the treatments were estimated with liver function tests, oxidative stress parameters, apoptotic parameters, histopathological examination, and hydroxyproline contents. Results showed that the combination of Nilotinib and stem cell-conditioned media had more antifibrotic effects than each one alone ( P value < 0.001).
Competing Interests: The authors declare that they have no conflict of interest.
(Copyright © 2020 Gamal Shiha et al.)
Databáze: MEDLINE
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