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Thiamine (T) deficient state and various functional and morphological changes in rat liver were induced, after several days, with T antagonists, oxythiamine (OT) or pyrithiamine (PT), and a thiamine deficient diet (TDD). The relationship between the extent of liver damage and T levels in blood, liver and urine were studied in OT treated rats fed a TDD (OTD group). PT treated rats fed a TDD (PTD group), OT treated rats (OT group), PT treated rats (PT group) and rats fed a TDD (TDD group). The T levels in blood and liver of OT group, PT group, OTD group, PTD group and TDD group were 89% and 91%, 76% and 88%, 25% and 14%, 33% and 16%, 24% and 15% compared with the data in the control group, respectively. Effects of OT or PT on T levels were not remarkable in some cases, and such may be due to the duration time of T antagonists, which was considered to be 3-15 hours in PT treated rats, and 0-18 hours in PT treated rats, as assessed by urinary T measurements. Treatment of T antagonist twice daily is recommended to obtain a definite T deficient state. Our results suggest that the extent of liver damage is related to the T levels in tissue.

We observed under light and electron microscopes morphological changes in the brains of rats in a thiamine deficient state as induced by an oxythiamine, pyrithiamine and thiamine deficient diet (OT, PT and TDD). We simultaneously determined thiamine levels in the whole brain of rats. The rats were separated into six groups-normal control, OT or PT treated rats (OT or PT group), OT or PT treated rats fed a TDD (OTD or PTD group), rats fed a TDD (TDD group)-. Microscopically, there were symmetrically distributed lesions containing spongy reticulation mainly in the vestibular nucleus. Electron microscopically, we found more advanced lesions in the OTD and PTD groups than in the TDD group. These ultrastructural changes were seen in the vicinity of capillaries and such consisted of abnormal endothelial cells and pericytes, excrescence of microglias, swelling or vacuolation of astrocytes, nerve cells containing distorted organelle and myelin degeneration, besides extracellular edema. The thiamine level in the TDD group decreased to 56% that of control. No effect of OT on the thiamine level was observed either in case of ingestion of a regular diet or when TDD was given. On the other hand, the thiamine level decreased to 43% in the PT group and to 17-23 in PTD. These results suggest that encephalopathy caused by the OT or PT-induced thiamine deficiency has the same selective vulnerable site as does the TDD-induced deficiency, however cellular sensitivity may differ slightly with the various ultrastructural changes.

We observed under light and electron microscopes morphological changes in the rat sciatic nerve during the early stages of a thiamine deficient state as induced by a pyrithiamine (PT: 50 microgram/100g X 6 days) and thiamine deficient diet (TDD). We simultaneously determined thiamine levels in the whole sciatic nerve of rats. Experiments were undertaken with normal control, TDD (rats fed a TDD), PT (PT treated rats) and PTD (PT treated rats fed a TDD) groups. Microscopically, there were numerous shrunken myelinated axons with myelin ovoids of folds in the PT group and many swollen ones in the PTD group. Electron microscopically, we found more advanced lesions in the PTD group than in the other groups. These ultrastructural changes were swelling of Schwann cells, enlarged rough-surfaced endoplasmic reticulum, axonal degeneration with shrinkage, loss of organelle or abnormal myelin sheath, and proliferation of fibroblasts. The thiamine level in the PTD group decreased to 18 approximately 30% that of control in proportion to the morphological changes. On the other hand, the thiamine level in the PT group (55 approximately 61%) decreased slightly more than that of the TDD group (50 approximately 56%), but changes in morphology were vice versa. These results suggest that the morphological changes in the sciatic nerve caused by PT-induced thiamine deficiency differs from changes seen in cases of dying-back neuropathy caused by TDD-induced deficiency, and that PT itself directly affects the nervous system