title: Immunotoxicological effects of streptozotocin and alloxan: in vitro and in vivo studies.
abstract: Streptozotocin (STZ) and alloxan (ALX), widely used to induce diabetes in experimental animals, have different structures and mechanisms of action. We investigated those effects of these drugs on the immune system that might influence engraftment efficiency and graft survival in transplantation models, and their cytotoxicity on hematopoietic cell lines. We used the minimum dose to induce diabetes in a mouse, i.e. 180 mg/kg i.v. STZ and 75 mg/kg i.v. ALX. Both groups exhibited significant decrease in body weight during 4 days post-treatment as compared to controls. We found that blood glucose in ALX-injected mice increased faster than in STZ-injected mice. The total number of recovered splenocytes was lower in STZ-injected animals than in ALX-injected animals. The survival periods of rat islet grafts in recipient mice were longer and more diverse in STZ-injected recipients (7-24 days) compared to ALX-injected recipients (6-7 days). The in vitro study showed that ALX was less cytotoxic in cell lines with IC50 values of 2809, 3679 and >4000 μg/ml for HL60, K562 and C1498 cells respectively. STZ was more toxic, especially in HL60 cells, with IC50 values of 11.7, 904 and 1024 μg/ml for HL60, K562 and C1498 cells respectively. Furthermore, in response to concanavalin A (Con-A), splenocytes from STZ-injected mice produced higher amounts of interferon-gamma (IFN-γ) than those from ALX-injected mice. In conclusion, STZ was more cytotoxic than ALX in vitro and in vivo. STZ caused lymphocytopenia, which may result in longer graft survival in STZ-treated animals than in ALX-treated animals.
authors.affiliation: Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Human Anatomy, School of Medicine, Ahfad University for Women, Omdurman, Sudan.
authors.forename: Randa A Hadi
authors.initials: RA
authors.lastname: Diab
authors.affiliation: Division of Experimental Cancer Medicine, KFC, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mona
authors.initials: M
authors.lastname: Fares
authors.affiliation: Division of Experimental Cancer Medicine, KFC, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Manuchehr
authors.initials: M
authors.lastname: Abedi-Valugerdi
authors.affiliation: Division of Transplantation, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kumagai-Braesch
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Holgersson
authors.affiliation: Division of Experimental Cancer Medicine, KFC, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Clinical Research Center, Novum, Karolinska University Hospital-Huddinge, Stockholm, Sweden. Electronic address: moustapha.hassan@ki.se.
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hassan
mesh_terms: D000496:Alloxan / Q000276:immunology / Q000633:toxicity*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods / Q000401:mortality; D020014:K562 Cells; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D011917:Rats, Inbred Lew; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013311:Streptozocin / Q000276:immunology / Q000633:toxicity*; D015996:Survival Rate; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D013311:Streptozocin; D000496:Alloxan
keywords: Alloxan; Diabetes; Islets; Streptozotocin; Toxicity