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The cytoplasmic reduction-oxidation state of some NAD-linked reactions has been investigated in the liver in vivo under normal and diabetic conditions with or without CoQ7 administration.1. In the liver, the close relationships among lactate/pyruvate, malate/oxaloacetate and glycerol-1-phosphate/dihydroxyacetone phosphate ratios were found in all the metabolic conditions studied. In diabetic rats, these systems were found to be more reduced.2. CoQ7 administration to diabetic rats for four days intramuscularly tended to restore these ratios to normal. This effect was followed by a significant drop in malate concentration.Present findings would indicate that the effect of CoQ7 on the reduced state in diabetic rats seems to be mediated via malate removal.

1. The CoQ content of whole rat liver increased significantly as compared with the control after the intramuscular administration of CoQ7, CoQ9 or CoQ10, but increased slightly after the administration of CoQ2 or CoQ6. In the mitochondrial fraction, CoQ content increased only after the administration of CoQ7 or CoQ9. After the administration of CoQ compounds, paper chromatography of the liver extract showed a corresponding increase of CoQ.2. Twenty-four hours after giving CoQ7-14C to rats, the percentage recovery in the liver administered was found to be 12.3±0.47% of the dose of 14C administered intramuscularly or 11.8±1.37% of those given orally. When the CoQ fraction was developed paperchromatographically, the radioactivity on the actigram was found in the CoQ7 portion exclusively.

Thioctic acid was determined microbiologically using Streptococcus faecalis 10 C1. The serum level of thioctic acid was frequently found to be reduced in patients with diseases of the liver, especially in those with liver cirrhosis. In patients with severe diabetes mellitus and in some patients with polyneuritis or arteriosclerosis, the serum level of thioctic acid was also found to be decreased.

1. Urinary excretion of PaA and the increase in the excretion of the vitamin following pantothenate administration were measured in 52 patients with various liver damages. Mutual relations with various liver functions were also studied.2. Both urinary PaA and the increase in excretion following intramuscular administration of the vitamin were reduced in most patients in comparison with those in normal adults.In relatively severe cases, increase in PaA excretion following intramuscular administration of the vitamin was frequently found to be greater than that of normal persons.3. Correlation was found between PaA excretion and various liver functions, especially, TTT, serum cholesterol ester ratio, hippuric acid synthesis and blood pyruvate level.4. The results mentioned above led to the conclusion that a metabolic disturbance of PaA may exist in liver damages leading to the impairment of liver functions, especially, hippuric acid synthesis, and the metabolism of α-keto acid and cholesterol.

1. Lipoic acid or lipoamide administered orally to animals seemed to be easily absorbed from the digestive tract and to be eliminated in the urine largely as the oxidation products of these substances.2. Lipoamide was easily converted to lipoic acid both in the in vitro and in vivo experiments.3. Urinary excretion of S35-compounds, after administering S35-lipoic acid or S35-lipoamide, was found to be increased in the rats poisoned with CCl4 or those with alloxan diabetes as compared with normal rats.

1. The treatment of diabetic neuropathy with daily oral dose of 10mg of CoQ7 for 3 to 13 weeks was made and obtained considerable relief from neurological subjective symptoms such as pain and paresthesia of extremities, and calftenderness as well as improvement in the abnormal threshold of vibratory perception on fingers and toes.2. Impaired metabolism of α-keto acids observed in diabetics, as measured by the increase of urinary pyruvate and α-ketoglutarate after intravenous fructose loading, was improved considerably after oral administration of CoQ7.