Summary
Wistar strain of rats received daily intraperitoneal or oral administration of Triparanol, 250 mg per kg of body weight or 20,25-diazacholesterol either 30 mg or 60 mg per kg of body weight starting at the age of 5 days old. Prominent intracytoplasmic osmiophilic inclusions identical to those found in the rats treated with AY9944 (Suzukiet al., 1973) and degeneration of myelin sheaths and oligodendroglia were seen in the myelinating white matter of rats sacrificed after 3, 6, and 9 injections of Triparanol.
In diazacholesterol-treated animals, a few identical inclusions were seen in the cortical neurons but only slight changes were seen in oligodendroglia. Biochemical analysis of the brains of the rats receiving Triparanol revealed a large accumulation ofΔ 7,24-cholestadiene-3β-ol and lesser amounts of desmosterol. The brains of the animals treated with diazacholesterol revealed massive accumulation of desmosterol and a minor sterol component, probablyΔ 5,7,24-cholestatriene-3β-ol. Since AY9944, which results in a massive accumulation of 7 dehydrocholesterol (Δ 5,7-cholestadiene-3β-ol) and two other sterols,Δ 7,24-cholestadiene-3β-ol andΔ 5,7,24-cholestatriene-3β-ol, will produce identical neuropathological lesions to those seen in Triparanol treated animals, and since the lesion produced in diazacholesterol treated animals was very slight, there appears to be a correlation between the presence of sterols with a double bond at the 7-position and neuropathological lesions in young rats.
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Suzuki, K., Zagoren, J.C., Chen, S.M. et al. Effects of triparanol and 20,25-diazacholesterol in CNS of rat: Morphological and biochemical studies. Acta Neuropathol 29, 141–156 (1974). https://doi.org/10.1007/BF00684773
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DOI: https://doi.org/10.1007/BF00684773