Squalene protects mice bone marrow hematopoietic and mesenchymal stem cells against high-dose cisplatin in vivo by restoring antioxidant balance: implications in cancer chemotherapy

1128 Background: There is an urgent need to develop selective cytoprotective agent to protect normal tissues without protecting malignant tumors from cytotoxic chemotherapy. We have previously shown that squalene, an isoprenoid antioxidant showed in vitro cytoprotective activity in a bone marrow versus neuroblastoma model of cisplatin-induced toxicity (Das B et al. Eur J Cancer, 2003; 39:2556-2565). Here we investigated the in vivo cytoprotection of squalene in a mouse model of cisplatin-toxicity against normal versus neuroblastoma xenograft. Methods: cisplatin (8-15mg/kg body weight) was injected i.p. to Balb/c mice with or without squalene (100mg/kg mixed with Intralipid) 3hrs before cisplatin injection. Bone marrow was collected five days after drug injection, and CFU assays were performed. Toxicity to mesenchymal stem cells was measured by culturing mesenchymal colonies in special mesencult media (Stem Cell Inc. Vancouver BC). Renal toxicity was measured by plasma BUN level. Oxidative stress parameter was measured by measuring GSH, GST, SOD, and GSpx activities by established biochemical methods (Chemicon International, USA). Results: cisplatin, 15mg/kg dose reduced BM colony formation by 51%, whereas the addition of squalene reduced BM colony formation by only 15%, suggesting 36% protection (p