There is increasing evidence that aldehydic molecules generated endogenously during the process of lipid peroxidation are causally involved in most of the pathophysiological effects associated with oxidative stress in cells and tissues. 4-Hydroxy-2-nonenal (HNE), among them, is believed to be largely responsible for cytopathological effects observed during oxidative stress in vivo and has been achieved the status of one of the best recognized and most studied of the cytotoxic products of lipid peroxidation. In the present review, I provide a comprehensive summary on HNE as a marker of oxidative stress.
A large number of so-called diet foods containing Citrus aurantium (CA) and its active constituent, synephrine, for suppressing body fat accumulation are currently on the market. However, only one human study has demonstrated the efficacy of CA, and its potential cardiotoxicity has been reported in a rat study. Therefore, we investigated the safety of CA and its suppressive effect against body fat accumulation in rats. High-fat (20% (w/w)) diets containing CA (synephrine content, 6.4%) at 0, 40, 200, 1,000, and 5,000 mg/kg diet were fed to rats ad libitum for 79 days. For dieting, the recommended daily intake of CA in many dietary supplements ranges from 100 to 1,000 mg/day, and the amount used in this experiment was approximately equivalent to 40 and/or 200 mg/kg diet. In the 5,000 mg/kg CA group, the adrenaline and dopamine concentrations in plasma were significantly higher, perirenal fat pad weight was significantly lower, and body weight tended to be lower than in the control group. Although no abnormalities of serum clinical and biochemical parameters were observed except for adrenaline and dopamine, and also no histopathological abnormalities were evident in the heart, heart weight in the 5,000 mg/kg CA group was significantly lower than in the control group. Therefore, it is necessary to examine more precisely the potential cardiotoxicity caused by excess intake of CA. Particularly, the elucidation of influences of the simultaneous intake of CA and some stimulants, such as caffeine, awaits further characterization.
We compared relative copper-binding capacities of cellular components and determined the substance that dominantly sequesters excess copper incorporated into bakers' yeast cells before the copper homeostasis systems start to operate. The fluorescent chelator calcein, whose fluorescence is quenched by its binding with copper, was used for estimation of the copper-binding capacities. The copper-binding capacity was assessed by the degree of competition of a sample against calcein for copper. The result indicated that GSH and a whole of the other low-molecular-weight substances had comparable copper-binding capacities, which were a little higher than that of cytosolic proteins as a whole, when compared at their relative cellular concentrations. However, a centrifugal ultrafiltration study showed that essentially all the copper ions incorporated in cells after treatment with 50 μM CuCl2 for 5 min were not filterable, indicating their binding to high-molecular-weight substances, namely cytosolic proteins. In the direct fluorescence measurement with calcein-loaded cells, no labile copper was detected in either wild-type yeast or GSH-deficient mutant upon treatment with 50 μM CuCl2, supporting the notion of the copper buffering by the cytosolic proteins under the in vivo conditions. This property of the proteins may not only play a part in cell's resistance against copper but also it may necessitate the role of copper chaperones in the intracellular trafficking of copper to target proteins.