VINCRISTINE-INDUCED NEUROTOXICITY IN RATS MEDIATED BY UPREGULATION OF INOS, IBA1, NESTIN, PARP AND CASPASE 3: AMELIORATIVE EFFECT OF ERYTHROPOIETIN AND THYMOQUINONE | ||||
Assiut Veterinary Medical Journal | ||||
Article 15, Volume 69, Issue 179, October 2023, Page 172-185 PDF (1.65 MB) | ||||
Document Type: Research article | ||||
DOI: 10.21608/avmj.2023.223481.1171 | ||||
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Authors | ||||
SAHAR A AHMED 1; HOSSAM EL-DIN M OMAR2; MAHMOUD SOLIMAN3; ABO BAKR ABDEL SHAKOR4; MANAL M SAYED5; OMNIA HM OMAR6; SARY KH. ABD ELGHAFFAR 7 | ||||
1Department of Molecular Biology, Molecular Biology Researches & Studies Institute, Assiut University, Assiut - Egypt. | ||||
22Department of Zoology and Entomology, Faculty of Science, Assiut University, Assiut, Egypt Department of Basic Science, School of Biotechnology, Badr University in Assiut, Egypt | ||||
3Laboratory of Pathology, College of Veterinary Medicine, Chonnam National University, South Korea | ||||
4Department of Zoology and Entomology, Faculty of Science, Assiut University, Assiut, Egypt | ||||
5Department of Chemistry, Animal Health Research Institute, Assiut Lab. | ||||
6Assiut International Center of Nanomedicine, El-Rajhy Liver Hospital, Assiut University, Assiut, Egypt | ||||
7Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Assiut University, Egypt 6Department of Pathology and Clinical Pathology, School of Veterinary Medicine, Badr University in Assiut, Egypt | ||||
Abstract | ||||
Vincristine (VCR) is an effective anticancer medication, although it has neurotoxic side effects. Erythropoietin (EPO) is the main regulator of erythropoiesis. Thymoquinone (TQ) protects brain cells from oxidative stress that causes neurodegenerative disorders such as Alzheimer's and Parkinson's. This study aims to investigate the VCR toxicity on the cerebrum as well as the possible neuroprotective effects of TQ and EPO against VCR toxicity in a rat model. An intraperitoneal injection of VCR (150 μg/kg) 3 times a week for 5 weeks caused marked histopathological changes in the brain such as neuronal degeneration with aggregations of glial cells around the degenerated neurons (satellitosis), congestion of blood vessels and severe demyelination in the white matter of the cerebrum. VCR considerably increased nestin, iBA1 and iNOS expression, while synaptophysin expression decreased. It also caused upregulation of caspase 3 and PARP expression, resulting in hemorrhage, demyelination, and neuronal degeneration. Treatment of rats with TQ or EPO either alone or in combination improved histopathological changes through down-regulation of nestin, iBA1, iNOS, caspase 3 and PARP. It was concluded that EPO and TQ ameliorate the neurotoxic effect of VCR on the cerebrum, however, a synergetic effect was evident when TQ and EPO were combined. | ||||
Keywords | ||||
Vincristine; brain; erythropoietin; thymoquinone; apoptosis; demyelination | ||||
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