Evidence for Reduced SuperoxideNitric Oxide Interaction

The effects of overexpression of Cu2/Zn2 superoxide dismutase-1 (SOD-1) on indexes of renal injury were compared in 5-month-old nontransgenic (NTg) db/db mice and db/db mice hemizygous for the human SOD-1 transgene (SOD-Tg). Both diabetic groups exhibited similar hyperglycemia and weight gain. However, in NTg-db/db mice, albuminuria, glomerular accumulation of immunoreactive transforming growth factor-, colla-gen 1(IV) , nitrotyrosine, and mesangial matrix were all significantly increased compared with either non-diabetic mice or SOD-Tg-db/db. SOD-1 activity and reduced glutathione levels were higher, whereas malon-dialdehyde content was lower, in the renal cortex of SOD-Tg-db/db compared with NTg-db/db mice, consis-tent with a renal antioxidant effect in the transgeni