Retinoic Acid Potentiates the Therapeutic Efficiency of Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs) against Cisplatin-Induced Hepatotoxicity in Rats
(1) Background: Hepatotoxicity is a common health problem, and oxidative stress plays a crucial role in its underlying mechanisms. We inspected the possible effect of retinoic acid (RA) in the potentiation of hepatoprotective effect of bone marrow mesenchymal stem cells (BM-MSCs) against Cisplatin (...
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MDPI AG
2022-09-01
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| Series: | Scientia Pharmaceutica |
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| Online Access: | https://www.mdpi.com/2218-0532/90/4/58 |
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| author | Maha M. Azzam Abdelaziz M. Hussein Basma H. Marghani Nashwa M. Barakat Mohsen M. M. Khedr Nabil Abu Heakel |
| author_facet | Maha M. Azzam Abdelaziz M. Hussein Basma H. Marghani Nashwa M. Barakat Mohsen M. M. Khedr Nabil Abu Heakel |
| author_sort | Maha M. Azzam |
| collection | DOAJ |
| description | (1) Background: Hepatotoxicity is a common health problem, and oxidative stress plays a crucial role in its underlying mechanisms. We inspected the possible effect of retinoic acid (RA) in the potentiation of hepatoprotective effect of bone marrow mesenchymal stem cells (BM-MSCs) against Cisplatin (Cis)-induced hepatotoxicity. (2) Methods: 60 male Sprague Dawley rats (SD) were separated randomly and designated to six main equal groups as follows: (1) Control group, (2) Cis group (rats got Cis 7 mg/Kg i.p.), (3) Cis + vehicle group (as group 2, but rats received the (vehicle) culture media of BM-MSCs), (4) Cis as in group 2 + BM-MSCs (1x10<sup>6</sup>), (5) Cis as for group 2 + RA 1 mg/Kg i.p., and (6) Cis and BM-MSCs as for group 3 + RA as for group 4. Liver injury was assessed by measuring liver enzymes (ALT, AST), while liver toxicity was evaluated by histopathological examination. Apoptotic marker caspase-3 protein was detected immunohistochemically. Real time PCR was performed to detect NADPH oxidase and TNF-α at transcription levels. Oxidative stress was investigated by colorimetric measurement of MDA, GSH and catalase. (3) Results: Contrary to the Cis group (<i>p</i> < 0.05), BM-MSCs/RA supplementation resulted in a substantial decrease in serum levels of hepatic impairment indicators such as ALT, AST and oxidative stress markers such as MDA, as well as an increase in hepatic GSH, Catalase, and a decrease in expression of TNF-α and downregulation of NADPH oxidase. The improvement after therapy with BM-MSCs/RA was confirmed by histopathological examination. Moreover, the downregulation of caspase-3 in liver tissue after BM-MSCs/RA treatment was validated by immunohistochemistry investigation. (4) Conclusions: BM-MSCs and RA attenuated Cis induced hepatotoxicity through downregulation of oxidative stress resulted in modulation of anti-inflammatory TNF-α and apoptosis caspase-3 indicating a promising role in hepatotoxicity. |
| first_indexed | 2024-03-09T15:53:12Z |
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| institution | Directory Open Access Journal |
| issn | 0036-8709 2218-0532 |
| language | English |
| last_indexed | 2024-03-09T15:53:12Z |
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| spelling | doaj.art-09cf3cafc9f84801b668d30b3be2657a2023-11-24T17:51:25ZengMDPI AGScientia Pharmaceutica0036-87092218-05322022-09-019045810.3390/scipharm90040058Retinoic Acid Potentiates the Therapeutic Efficiency of Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs) against Cisplatin-Induced Hepatotoxicity in RatsMaha M. Azzam0Abdelaziz M. Hussein1Basma H. Marghani2Nashwa M. Barakat3Mohsen M. M. Khedr4Nabil Abu Heakel5Department of Physiology, Mansoura Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Medical Physiology, Mansoura Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Physiology, Mansoura Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, EgyptUrology & Nephrology Center, Mansoura University, Mansoura 35516, EgyptDepartment of Chemistry, Faculty of Science, Port Said University, Port Said 42521, EgyptDepartment of Physiology, Mansoura Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt(1) Background: Hepatotoxicity is a common health problem, and oxidative stress plays a crucial role in its underlying mechanisms. We inspected the possible effect of retinoic acid (RA) in the potentiation of hepatoprotective effect of bone marrow mesenchymal stem cells (BM-MSCs) against Cisplatin (Cis)-induced hepatotoxicity. (2) Methods: 60 male Sprague Dawley rats (SD) were separated randomly and designated to six main equal groups as follows: (1) Control group, (2) Cis group (rats got Cis 7 mg/Kg i.p.), (3) Cis + vehicle group (as group 2, but rats received the (vehicle) culture media of BM-MSCs), (4) Cis as in group 2 + BM-MSCs (1x10<sup>6</sup>), (5) Cis as for group 2 + RA 1 mg/Kg i.p., and (6) Cis and BM-MSCs as for group 3 + RA as for group 4. Liver injury was assessed by measuring liver enzymes (ALT, AST), while liver toxicity was evaluated by histopathological examination. Apoptotic marker caspase-3 protein was detected immunohistochemically. Real time PCR was performed to detect NADPH oxidase and TNF-α at transcription levels. Oxidative stress was investigated by colorimetric measurement of MDA, GSH and catalase. (3) Results: Contrary to the Cis group (<i>p</i> < 0.05), BM-MSCs/RA supplementation resulted in a substantial decrease in serum levels of hepatic impairment indicators such as ALT, AST and oxidative stress markers such as MDA, as well as an increase in hepatic GSH, Catalase, and a decrease in expression of TNF-α and downregulation of NADPH oxidase. The improvement after therapy with BM-MSCs/RA was confirmed by histopathological examination. Moreover, the downregulation of caspase-3 in liver tissue after BM-MSCs/RA treatment was validated by immunohistochemistry investigation. (4) Conclusions: BM-MSCs and RA attenuated Cis induced hepatotoxicity through downregulation of oxidative stress resulted in modulation of anti-inflammatory TNF-α and apoptosis caspase-3 indicating a promising role in hepatotoxicity.https://www.mdpi.com/2218-0532/90/4/58cisplatin hepatotoxicityBM-MSCsretinoic acidoxidative stressNADPH oxidaseapoptosis |
| spellingShingle | Maha M. Azzam Abdelaziz M. Hussein Basma H. Marghani Nashwa M. Barakat Mohsen M. M. Khedr Nabil Abu Heakel Retinoic Acid Potentiates the Therapeutic Efficiency of Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs) against Cisplatin-Induced Hepatotoxicity in Rats Scientia Pharmaceutica cisplatin hepatotoxicity BM-MSCs retinoic acid oxidative stress NADPH oxidase apoptosis |
| title | Retinoic Acid Potentiates the Therapeutic Efficiency of Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs) against Cisplatin-Induced Hepatotoxicity in Rats |
| title_full | Retinoic Acid Potentiates the Therapeutic Efficiency of Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs) against Cisplatin-Induced Hepatotoxicity in Rats |
| title_fullStr | Retinoic Acid Potentiates the Therapeutic Efficiency of Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs) against Cisplatin-Induced Hepatotoxicity in Rats |
| title_full_unstemmed | Retinoic Acid Potentiates the Therapeutic Efficiency of Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs) against Cisplatin-Induced Hepatotoxicity in Rats |
| title_short | Retinoic Acid Potentiates the Therapeutic Efficiency of Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs) against Cisplatin-Induced Hepatotoxicity in Rats |
| title_sort | retinoic acid potentiates the therapeutic efficiency of bone marrow derived mesenchymal stem cells bm mscs against cisplatin induced hepatotoxicity in rats |
| topic | cisplatin hepatotoxicity BM-MSCs retinoic acid oxidative stress NADPH oxidase apoptosis |
| url | https://www.mdpi.com/2218-0532/90/4/58 |
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