extract supplementation alleviates doxorubicin-induced neurotoxicity in rats | ||||
| Egyptian Pharmaceutical Journal | ||||
| Volume 21, Issue 1, January 2022, Page 46-56 PDF (5.51 MB) | ||||
| DOI: 10.4103/epj.epj_56_21 | ||||
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| Authors | ||||
| Samya Mahmoud Ahmed; Marwa A. Masoud | ||||
| Abstract | ||||
| Background Doxorubicin (DOX) is widely used to treat many human cancers, but significant brain damage limits its clinical application. Objectives To investigate the neuroprotective activity of extract (TME) against DOX-induced neurotoxicity in rats. Materials and methods The first group served as a normal control; the second group served as a positive control which was treated with DOX (2.5 mg/kg; dissolved in saline; intraperitoneal three times/week for 2 weeks,); the third group was treated with TME at a dose of 100 mg/kg; the fourth group was pretreated with TME for 2 weeks and then coadministrated with DOX for other 2 weeks; the fifth and sixth groups were treated with DOX for 2 weeks and then posttreated with two doses of TME (100, 200 mg/kg), respectively, for another 2 weeks. The experiment lasted for 4 weeks; brain tissue samples were harvested for the measurement of toxicity such as oxidative stress, inflammation, apoptosis, neurodegeneration, and histopathological examinations. Results and conclusion DOX-treated animals showed a reduction in glutathione and superoxide dismutase along with a raise in malondialdehyde, nitric oxide, and myeloperoxidase. Also, it caused an increase in caspase-3, indicating an increased propensity for cell death, acetylcholinesterase, extracellular signal-regulated kinase, mammalian target of rapamycin with concomitant decrease in brain-derived neurotrophic factor. However, administration of TME significantly improved oxidative stress alterations, brain-derived neurotrophic factor, and apoptosis. Histological assessments of brain tissues supported the obtained biochemical finding. In conclusion, our findings disclose a potent protective role of TME by activating antioxidant, anti-inflammatory, anti-apoptotic, and neurogenesis effects, which may contribute to the safe use of DOX in cancer treatment. | ||||
| Keywords | ||||
| Doxorubicin; brain damage; Oxidative Stress; apoptosis; Terminalia muelleri extract | ||||
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