Enhancement by streptozotocin of O2- radical generation by the xanthine oxidase system of pancreatic beta-cells.
Spin-trapping techniques and electron spin resonance (ESR) spectroscopy were used to study the relationship between the effect of streptozotocin (STZ) on pancreatic beta-cells and free radical formation by these cells. Results showed that STZ enhanced generation of the DMPO-OH radical adduct, which is a degradation product of the superoxide anion (O2-) in the presence of cellular components, in a hypoxanthine-xanthine oxidase (XOD) system with a homogenate of beta-cells. This enhancing effect was also observed in a system without cellular components; STZ increased the signal height due to the O2- radical in a concentration-dependent manner and caused a maximum of 150% enhancement at a concentration of 1.5 mM. Thus, STZ seemed to enhance the generation of the O2- radical in the XOD system, probably by some mechanism of its interaction with XOD. Pancreatic beta-cells exhibited a high XOD activity and a very low superoxide dismutase activity. Therefore, the present result supports the possibility that the cytotoxic effect of STZ is closely related to free radical generation in pancreatic beta-cells.
Nukatsuka
M
M
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Sakurai
H
H
Yoshimura
Y
Y
Nishida
M
M
Kawada
J
J
D000818:Animals; D000831:Animals, Newborn; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D007515:Islets of Langerhans / Q000201:enzymology*; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000031:analogs & derivatives / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D005609:Free Radicals; D013481:Superoxides; D013311:Streptozocin; D014969:Xanthine Oxidase