Conjugated dienes: A critical trait of lipoprotein oxidizability in renal fibrosis

Abstract

Background. We assessed whether a differential oxidizability of apolipoprotein B (apo B)-containing lipoproteins (LDL and VLDL) may explain the oxidative stress that we had observed at the onset of renal fibrosis in Zucker obese (ZO) rats (Nephrol Dial Transplant 2000, 15: 467-476). Methods. Ex vivo copper-induced oxidation of lipoproteins was performed in 1-, 3-, and 9-month-old ZO and age-matched lean (ZL) rats. LDL/VLDL oxidizability was determined by spectrophotometry at 234 nm by monitoring the formation of conjugated diene hydroperoxides. Results. A significant increase in lag time (reflecting the resistance to oxidation) was observed in ZO rats at 3 months while the maximal diene production (reflecting the amount of hydroperoxides formed during oxidation) was higher in ZO than in ZL rats as early as 1 month. Lipoproteins were larger in ZO than in ZL rats, as shown by their core to surface component ratio. Furthermore, ZO lipoproteins had increased vitamin E and polyunsaturated fatty acid (PUFA) content, with no change in vitamin E/PUFA ratio. Conclusions. Rather than oxidizability of apo B-containing lipoproteins, the ability of these molecules to produce high levels of conjugated dienes, which can act as toxic tissue messengers, appears to be a critical trait in the development of renal fibrosis in this rat model of obesity and renal fibrosis.