Squalene selectively protects mouse bone marrow progenitors against cisplatin and carboplatin-induced cytotoxicity in vivo without protecting tumor growth

Bikul Das, Roula Antoon, Rika Tsuchida, Shamim Lotfi, Olena Morozova, Walid Farhat, David Malkin, Gideon Koren, Herman Yeger and sylvain baruchel

Year 2008, Volume 10, Issue 10

Abstract

Squalene, an isoprenoid antioxidant is a potential cytoprotective agent against chemotherapy-induced toxicity. We have previously published that squalene protects light density bone marrow (LD-BM) cells against cisplatin-induced toxicity without protecting tumor cells in vitro. Here, we developed an in vivo mouse model of cisplatin and carboplatin-induced toxicity to further investigate squalene mediated LD-BM cytoprotection including the molecular mechanism behind selective cytoprotection. We found that squalene significantly reduced the body weight loss of cisplatin and carboplatin treated mice. LD-BM from squalene treated mice exhibited improved formation of hematopoietic colonies (CFU-GM). Furthermore, squalene also protected mesenchymal stem cell colonies (CFU-F) from cisplatin and carboplatin-induced toxicity. Squalene-induced protection was associated with decreased ROS and increased levels of glutathione and glutathione peroxidase/glutathione S-transferase. Importantly, squalene did not protect neuroblastoma, small cell carcinoma or medulloblastoma xenografts against cisplatin-induced toxicity. These results suggest that squalene is a potential candidate for future development as a cytoprotective agent against chemotherapeutic toxicity.

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