title: Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity.
abstract: Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without compromising its anticancer activity, thus leading to a dramatic increase of cancer cure rate from 25% to 75%. Hydration has been used in clinical practice to reduce CDDP-induced nephrotoxicity, but it cannot mitigate CDDP-induced gastrointestinal toxicity. The present work investigated whether sodium selenosulfate is a potential preventive agent for the gastrointestinal toxicity. In tumor-bearing mice, sodium selenosulfate was administered at a dose of 9.5 μmol/kg daily for 11 days, CDDP alone resulted in diarrhea by 88% on day 12, whereas the co-administration of CDDP and sodium selenosulfate dramatically reduced diarrhea to 6% (p<0.0001). Such a prominent protective effect promoted us to evaluate the safety potential of long-term sodium selenosulfate application. Mice were administered with sodium selenosulfate or sodium selenite for 55 days at the doses of 12.7 and 19 μmol/kg. The low-dose sodium selenite caused growth suppression and hepatotoxicity which were aggravated by the high-dose, leading to 40% mortality rate, but no toxic symptoms were observed in the two sodium selenosulfate groups. Altogether these results clearly show that sodium selenosulfate at an innocuous dose can markedly prevent CDDP-induced gastrointestinal toxicity.
authors.affiliation: School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Kang
authors.initials: K
authors.lastname: Sun
authors.forename: Lijuan
authors.initials: L
authors.lastname: Ni
authors.forename: Xufang
authors.initials: X
authors.lastname: Wang
authors.forename: Dongxu
authors.initials: D
authors.lastname: Wang
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity*; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D018036:Selenium Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D018038:Sodium Selenite / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D013431:Sulfates / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D018036:Selenium Compounds; D013431:Sulfates; D018038:Sodium Selenite; D002945:Cisplatin; C519925:sodium selenosulfate