The vitamin-E derivative U-83836-E in the low-dose streptozocin- treated mouse: effects on diabetes development.
Low-dose streptozocin-treated (LDS) mice were administered an inhibitor of lipid peroxidation, U-83836-E (a derivative of vitamin E), in order to observe its ability to alter the onset of diabetes. Ten or 20 mg/kg body wt. per day of U-83836-E were given to mice for 7 days and they were killed after 21 days. Results revealed that there was a significant increase in glycaemia in treated groups up to day 14 after which no further increase was noticed. Superoxide dismutase (SOD) assay showed that: (1) the LDS treatment significantly reduces SOD activity when compared with untreated controls (P < 0.005); (2) U-83836-E increases SOD levels (when compared with untreated controls); and (3) U-83836-E counteracts LDS treatment, since SOD activity is significantly higher with respect to that found in LDS-controls (P < 0.05), and SOD levels were significantly higher with respect to that found in Group 2 animals (P < 0.05), but significantly lower with respect to those found in groups 3 and 4 (P < 0.005). Moreover, malondialdehyde (MDA), the end-product of lipoperoxidation, was found at much higher levels in LDS controls than in the other groups and the lowest values were found in U-83836-E controls and in normoglycaemic animals treated with both streptozocin and U-83836-E. Morphological observations demonstrated that islet beta cells were of normal appearance in normoglycaemic animals of the treated groups. In conclusion, the in vivo inhibition of lipid peroxidation by this compound produces a limited but significant prevention of the islet beta cell destruction.
Papaccio
G
G
Institute of Anatomy, School of Medicine, Second University of Naples, Naples, Italy.
Baccari
G C
GC
Frascatore
S
S
Sellitti
S
S
Pisanti
F A
FA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D015331:Cohort Studies; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000737:chemistry / Q000201:enzymology / Q000648:ultrastructure; D007668:Kidney / Q000737:chemistry / Q000201:enzymology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D001786:Blood Glucose; D002839:Chromans; D016166:Free Radical Scavengers; D010879:Piperazines; C066382:U 78517F; D008315:Malondialdehyde; D013482:Superoxide Dismutase