Kunimitsu Wakamatsu

Effect of hyperthermia on glutathione peroxidase and lipid peroxidative damage in liver

1. 1.|Significant lipid peroxidation occurred both in rat and guinea pig liver in passive hyperthermia caused by a hot environment. In guinea pig, lipid peroxidation was greatly induced not only in liver homogenate but also in intracellular structures, such as mitochondria and microsomes. 2. 2.|In rat, hepatic cytosolic selenium glutathione peroxidase activities were greatly induced in hyperthermia, while hepatic cytosolic glutathione peroxidase activities in guinea pig were not affected in hyperthermia. 3. 3.|In both animals, hepatic cytosolic glutathione S-transferase, cytosolic superoxide dismutase, and catalase activities were not affected. 4. 4.|Since the peroxidation of lipids in biological membranes is a destructive phenomenon and is associated with a variety of cellular damage, hyperthermia greatly developed hypertrophy and vacuolized degeneration in hepatic cells. 5. 5.|In guinea pig, the activities of hepatic mitochondrial electron transport system, such as cytochrome c oxidase and cytochrome c reductase system were simultaneously inhibited in hyperthermia. 6. 6.|On the other hand, hepatic microsomal electron transport system, such as cytochrome P450 and aminopyrine N-demethylase activities were not seriously affected by hyperthermia. 7. 7.|In nuclei and mitochondria, 90-kDa heat shock induced proteins markedly expressed in liver. 8. 8.|Since hyperthermia greatly induces lipid peroxidation in liver, heat stress may have a potential impact on peroxidative damage in humans and animals.

Effects of the insecticide acephate on electron transfer in bovine heart mitochondria

The insecticide acephate shows toxic effects on carbohydrate metabolism in rats. The peak of13CO2 exhalation in rats following i.p. administration of13C-sodium acetate was significantly delayed by injection of acephate. The result suggests that carbohydrate metabolism is inhibited by the acephate dose. Acephate inhibited the electron transfer of respiration in isolated mitochondria. The activity of cytochrome c oxidase was severely inhibited by acephate at alkaline pH. The absorption spectrum of acephate had two peaks in the ultraviolet range at acid pH, while these two peaks disappeared and absorbance at 207–212 nm markedly increased at alkaline pH. The observations suggest that acephate dissolved in water may be easily modified at alkaline pH and only the modified reagent can react with cytochrome c oxidase.

Difference absorption spectrum of cytochrome c oxidase in the presence of acephate (N-acetvl O,S-dimethyl thiophosphoramide)

The alpha-peak in the difference spectrum between reduced cytochrome c oxidase (cytochrome a and a3) plus acephate (pH 9.5) and oxidized enzyme, shifted from 605 nm to 592 nm. The difference spectrum between reduced cytochrome c oxidase plus acephate (pH 9.5) and the reduced enzyme showed that the alpha and gamma peaks shifted to 592 nm and 432 nm, respectively. The effect of acephate on the spectrum of the reduced cytochrome c oxidase is similar to that of carbon monoxide.