Mohammed, Noor Ahmed (2017). The cyto-toxicity of some chemotherapeutic drugs on liver and kidney cell lines and the protective role of Ca2+ binding proteins. University of Birmingham. Ph.D.
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Mohammed17PhD.pdf
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Abstract
Cancer Chemotherapy treatment involves the administration of drugs to patients, these drugs mainly work by interacting with the cell cycle or inhibiting DNA synthesis. Unfortunately, the toxicity of these chemotherapy drugs is severe and can have serious side-effects on different tissues and organs of the body. In chemotherapy treatment about 85% of cancer patients exhibit some degree of liver or kidney damage. Therefore, the aim of this study was to investigate the cytotoxicity of some of the most commonly used chemotherapy drugs; Methotrexate (MTX), Etoposide, Cisplatin and Doxorubicin (DOX) on liver and kidney cell lines (HepG2, Huh7.5, COS-7 and HK2). Therefore, our focus were on studying the molecular mechanism by which these drugs cause cell death in liver and kidney cells. This study also investigated the effects of some Ca2+ binding proteins (RGN, SERCA1, SERCA2b, SPCA1a, SPCA2) to test their ability to decrease the toxicity of these chemotherapeutic drugs in liver and kidney cells. The results showed that Etoposide, Cisplatin and DOX induce cell death in both kidney and liver cell lines via several different pathways such as apoptosis, necrosis, and autophagy. The results presented here also showed that several of the drugs used induced cell death by a novel new autophagic pathway in liver and kidney cells. Our data also suggested that regucalcin (RGN) and the endoplasmic reticulum Ca2+ pumps (SERCA1 and SERCA2b), but not the secretory pathway Ca2+ pumps (SPCA1a and SPCA2) were able to protect against different types of chemotherapy-induced toxicity in liver and kidney cells. These new observations will help to build up our awareness of the diverse effect of these drugs have on liver and kidney cells and may also help to develop protective interventions and strategies in the future to reduce hepatotoxicity and nephrotoxicity caused by these drugs.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||
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| College/Faculty: | Colleges (2008 onwards) > College of Life & Environmental Sciences | |||||||||
| School or Department: | School of Biosciences | |||||||||
| Funders: | None/not applicable | |||||||||
| Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
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| URI: | http://etheses.bham.ac.uk/id/eprint/7530 |
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