Lipoperoxidation in hepatic subcellular compartments of diabetic rats

It is known that an accumulation of lipoperoxidative aldehydes malondialdehyde (MDA) and 4-hydroxynonenal (HNE) takes place in liver mitochondria during aging. The existence and role of an increased extra- and intra-cellular oxidative stress in diabetes, an aging-accelerating disease, is currently under discussion. This report offers evidence that lipoperoxidative aldehydes accumulate in liver microsomes and mitochondria at a higher rate in spontaneously diabetic BB/WOR rats than in control non-diabetic animals (HNE content, diabetes vs control: microsomes 80.6 +/- 19.9 vs 25.75 +/- 3.6 pmol/mg prot, p =.024; mitochondria 77.4 +/- 15.4 vs 26.5 +/- 3.5 pmol/mg prot, p =.0103). Liver subcellular fractions from diabetic rats, when exposed to the peroxidative stimulus ADP/Fe, developed more lipoperoxidative aldehydes than those from non diabetic rats (HNE amount, diabetes vs control: microsomes 3.60 +/- 0.37 vs 2.33 +/- 0.22 nmol/mg prot, p =.014; mitochondria 3.62 +/- 0.26 vs 2.30 +/- 0.17 nmol/mg prot, p =.0009). Liver subcellular fractions of diabetic rats developed more fluorescent chromolipids related to HNE-phospholipid adducts, either after in vitro peroxidation (microsomes: p =.0045; mitochondria: p =.0023) or by exposure to exogenous HNE (microsomes: p =.049; mitochondria: p =.0338). This higher susceptibility of diabetic liver membranes to the non-enzymatic attack of HNE may be due to an altered phospholipid composition. Moreover, a decreased activity of the HNE-metabolizing systems can be involved: diabetic liver mitochondria and microsomes were unable to consume exogenous HNE at the same rate as non-diabetic membranes; the difference was already significant after 5' incubation (microsomes p <.001; mitochondria p <.001). These data show an increased oxidative stress inside the hepatocytes of diabetic rats; the impairment of the HNE-metabolizing systems can play a key role in the maintenance and propagation of the damage. (C) 1999 Elsevier Science Inc