Attenuating the toxicity of cisplatin by using selenosulfate with reduced risk of selenium toxicity as compared with selenite.
It has been reported that high doses of sodium selenite can reduce side effects of cisplatin (CDDP) without compromising its antitumor activity, thus substantially enhancing the cure rate in tumor-bearing mice. However, the toxicity of selenite at high doses should be a concern. The present study revealed that selenosulfate had much lower toxicity, but possessed equal efficacy in selenium (Se) utilization, as compared with selenite at similar doses when used for the intervention of CDDP. In addition, Se accumulation in whole blood and kidney of mice treated with selenosulfate was highly correlated with the survival rate of mice treated with CDDP (both r>0.96 and both p<0.05), suggesting that whole blood Se is a potential clinical biomarker to predict host tolerance to CDDP. In either Se-deficient or -sufficient mice bearing solid tumors of hepatoma 22 (H22), selenosulfate did not disturb the therapeutic effect of CDDP on tumors but effectively attenuated the toxicity of CDDP. Furthermore, in a highly malignant cancer model, with Se-sufficient mice bearing ascitic H22 cells, 8 or 10 mg/kg CDDP alone only achieved a null or 25% cure rate, whereas coadministration of selenosulfate with the above two doses of CDDP achieved cure rates of 87.5% or 75%. These results together argue for consideration of selenosulfate as an agent to enhance the therapeutic efficacy of CDDP.
Zhang
Jinsong
J
University of Science and Technology of China, Hefei 230052, Anhui, PR China. zjszyzzc@mail.hf.ah.cn
Peng
Dungeng
D
Lu
Hongjuan
H
Liu
Qingliang
Q
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001201:Ascites / Q000188:drug therapy / Q000473:pathology; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012643:Selenium / Q000172:deficiency / Q000378:metabolism; D018036:Selenium Compounds / Q000494:pharmacology*; D018038:Sodium Selenite / Q000633:toxicity*; D013431:Sulfates / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D018036:Selenium Compounds; D013431:Sulfates; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D012643:Selenium; D018038:Sodium Selenite; D002945:Cisplatin; C519925:sodium selenosulfate