Fructose -- Protective?

Fructose and Tagatose Protect Against Oxidative Cell Injury by Iron Chelation


To further investigate the mechanism by which fructose affords protection against oxidative cell injury, cultured rat hepatocytes were exposed to cocaine (300 Image ) or nitrofurantoin (400 Image ). Both drugs elicited massively increased lactate dehydrogenase release. The addition of the ketohexoses Image -fructose (metabolized via glycolysis) or Image -tagatose (poor glycolytic substrate) significantly attenuated cocaine- and nitrofurantoin-induced cell injury, although both fructose and tagatose caused a rapid depletion of ATP and compromised the cellular energy charge. Furthermore, fructose, tagatose, and sorbose all inhibited in a concentration-dependent manner (0–16 mM) luminol-enhanced chemiluminescence (CL) in cell homogenates, indicating that these compounds inhibit the iron-dependent reactive oxygen species (ROS)-mediated peroxidation of luminol. Indeed, both Fe2+ and Fe3+ further increased cocaine-stimulated CL, which was markedly quenched following addition of the ketohexoses. The iron-independent formation of superoxide anion radicals (acetylated cytochrome c reduction) induced by the prooxidant drugs remained unaffected by fructose or tagatose. The iron-chelator deferoxamine similarly protected against prooxidant-induced cell injury. In contrast, the nonchelating aldohexoses Image -glucose and Image -galactose did not inhibit luminol CL nor did they protect against oxidative cell injury. These data indicate that ketohexoses can effectively protect against prooxidant-induced cell injury, independent of their glycolytic metabolism, by suppressing the iron-catalyzed formation of ROS. 
Cell protection by fructose is independent of adenosine triphosphate (ATP) levels in paracetamol injury to rat liver slices


Fructose protects cells against several types of injury but the mechanism of protection is uncertain. We have used paracetamol injury in rat liver slices as a model system to investigate the role of ATP levels in protection by fructose. Fructose depletes ATP levels in a concentration-dependent fashion in liver slices obtained from non-induced rats. Liver slices recover their ATP levels in the presence of fructose concentrations up to 10 mM. However, in the presence of 20 mM fructose, ATP levels are depleted for the duration of 240 min incubation. Adenine at 100 μM reverses the ATP depletion induced by 20 mM fructose in slices over 240 min incubation. Liver slices obtained from phenobarbitoneinduced rats were exposed to 10 mM paracetamol for 120 min and, then, incubated without paracetamol, with or without fructose for another 240 min. Introduction of 10 mM or 20 mM fructose in the second stage of incubation prevents paracetamol-induced injury. Fructose at 20 mM induces a rapid and marked depletion in slice ATP levels and these remain low throughout the second 240 min incubation period. Fructose at 10 mM maintains high ATP levels, even in paracetamol-treated slices. There is a profound protective effect against paracetamol-induced injury by either concentration. This suggests that protection is not dependent on high or on low ATP levels. Incubation of paracetamoltreated slices in the presence of 20 mM fructose plus 100 μM adenine in the second 240 min incubation period still results in the same level of protection as with 20 or 10 mM fructose alone while reversing the ATP depletion observed with 20 mM fructose.

Protection of cellular and mitochondrial functions against anoxic damage by fructose in perfused liver


In anoxic perfused liver, conversion of fructose to lactate was greatly increased to about 3 μmol/min per g liver. This increase in lactate implied that the same amount of ATP was also produced. The rate of metabolism of glucose was less than 10% of that of fructose, as judged by rate of production of lactate. In anoxic liver perfused with fructose, the ATP levels of both the tissue and mitochondria remained high, despite lack of oxygen, thus preventing enzyme leakage and preserving processes requiring ATP, such as bile excretion and urea formation. The mitochondrial oxidative phosphorylation capacity of anoxic liver perfused with fructose was also unimpaired. Spectral analysis of light transmitted through the liver revealed that the mitochondrial electron transfer system was in the completely reduced state during anoxia, indicating that the mitochondria were incapable of synthesizing ATP. These results suggest that fructose metabolism during anoxia resulted in sufficient production of ATP for maintaining the physiological functions of the cells and the oxidative phosphorylation capacity of their mitochondria.