Diabetes impairs the enzymatic disposal of 4-hydroxynonenal in rat liver

Traverso, Nicola; Menini, Stefano; Odetti, Patrizio; Pronzato, Maria Adelaide; Cottalasso, Damiano; Marinari, Umberto M.

doi:10.1016/s0891-5849(01)00811-5

Cited by 63 publications

(54 citation statements)

References 64 publications

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“…Increased accumulation of 4-HNE, a product of membrane LPO, has also been shown to be involved in tissue degeneration during diabetes (9,46). GST A4-4, the isoenzyme that metabolizes 4-HNE, was found to be induced in both mitochondria and cytosol of different tissues of diabetic animals.…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondrial dysfunction, apoptosis, and reduced ATP biosynthesis have all been implicated in type 1 diabetes (6,7). Accumulation of lipid peroxides, 4-hydroxynonenal (HNE), and malonedialdehyde (MDA) in mitochondria has also been reported in diabetic patients, possibly causing further damage to mitochondrial genetic and metabolic systems (8,9). Streptozotocin (STZ), an anolog of N-acetylglucosamine, has been used to generate animal models of type 1 diabetes.…”

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confidence: 99%

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Elevated Mitochondrial Cytochrome P450 2E1 and Glutathione S-Transferase A4-4 in Streptozotocin-Induced Diabetic Rats

et al. 2004

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Oxidative stress is an important factor in the etiology and pathogenesis of diabetes. We investigated changes in mitochondrial production of reactive oxygen species (ROS) and mitochondrial antioxidant defense systems in different tissues of streptozotocin (STZ)-induced diabetic rats. Our results show that increased ROS production and oxidative stress differentially affect mitochondrial and cytosolic glutathione (GSH) metabolism. Of the four tissues investigated, the pancreas, kidney, and brain appear to be affected more severely than the liver. We show a five-to eightfold increase of cytochrome P450 2E1 (CYP2E1) and glutathione Stransferase (GST) A4-4 levels in mitochondria from STZ-treated rat tissues compared with those in nondiabetic rat tissues, suggesting possible roles in the disease process. Transient transfection of COS cells with CYP2E1 cDNA caused a similar accumulation of CYP2E1 and GST A4-4 in mitochondria and increased production of mitochondrial ROS. Our results also show an increase in steady-state levels of Hsp70 in the mitochondrial and cytosolic fractions of different tissues of diabetic rats. These results indicate, for the first time, a marked increase in mitochondrial oxidative stress in target tissues of STZ-treated rats and implicate a direct role for mitochondrial CYP2E1 in the generation of intramitochondrial ROS.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Elevated Mitochondrial Cytochrome P450 2E1 and Glutathione S-Transferase A4-4 in Streptozotocin-Induced Diabetic Rats

et al. 2004

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“…Formation of HNE was studied also by Traverso et al (2002) in liver microsomes and mitochondria of rats with DM. These authors found increased formation of MDA and HNE in the group of diabetic rats compared to control group and increased rate of lipoperoxidation in membranes of diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

Influence of pyridoxylidene aminoguanidine on biomarkers of the oxidative stress and selected metabolic parameters of rats with diabetes mellitus

Országhová¹,

Liptáková²,

Muchová³

et al. 2009

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Abstract. Oxidative damage is considered to play an important role in the pathogenesis of several diseases, such as diabetes mellitus (DM), atherosclerosis, cardiovascular complications and chronic renal failure. DM is associated with the oxidative stress and formation of advanced glycation end products (AGEs). Different drugs inhibit oxidative stress and formation of advanced glycation end products. Aminoguanidine (AG) has been proposed as a drug of potential benefit in prophylaxis of the complications of DM. Recent reports show a pro-oxidant activity of AG. Therefore we examined the effect of structural analogue of AG, its Schiff base with pyridoxal -pyridoxylidene aminoguanidine (PAG) on the level of selected markers of oxidative stress. We found that PAG decreased total damage to DNA in controls as well as in diabetic group of rats. However, we also found that PAG supplementation increases susceptibility of lipoproteins to oxidation and formation of conjugated dienes in both, diabetic as well as control animals. Its administration to diabetic rats decreases antioxidant capacity of plasma. Therefore, it is necessary to search for other structural modifications of AG that would combine its higher anti-diabetic activity with less toxicity.

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“…Pancreatic islets from type-2 diabetic patients are positively stained with HNE, suggesting that oxidative stress through lipid peroxidation could contribute to the reduced beta-cell mass and islet-cell injury (Sakuraba et al, 2002). An increased level of HNE-modified proteins is reported in the pancreatic beta cells of Goto Kakizaki rats as a result of hyperglycaemia (Ihara et al, 1999); and accumulation of HNE is observed in liver of diabetic rats due to the impairment of HNE-metabolizing enzymes (Traverso et al, 1998(Traverso et al, , 2002. Diabetic mice under a high fat diet exhibit increased HNE adducts levels in temporal lobes relative to control (Lyn-Cook et al, 2009), and HNE conjugation of GLUT3, the glucose transporter present in neurons, is increased in the hippocampus of diabetic rats subjected to stress (Reagan et al, 2000).…”

Section: Lipid Peroxidation 420mentioning

confidence: 99%