The 100-fold increase in toxicity of intraperitoneal (i.p.) rather than orally administered 2-t-butyl-4-methoxyphenol (BHA) is adduced to the depressive effect which this compound exerts on the contractility of the gut musculature. A structure/activity relation study shows the t-butyl group on the benzene ring as being the major determinant of i.p. BHA toxicity. Contractile activity, elicited by field electrical stimulation, acetylcholine or Ba2+, of the ileum longitudinal muscle preparation from BHA-treated rats was greatly reduced 30 min after i.p. injection, and almost absent during the subsequent 48 h. Electron-microscope examination of ileum longitudinal muscle also showed partial destruction of cell membranes 4 h after BHA administration with subsequent mitochondrial swelling and destruction of cristae, myofibrillar fragmentation and cell necrosis. Comparable suppression of contractile activity and morphological damage were observed in BHA or t-butylbenzene incubated ileum segments where longitudinal smooth muscle contractility was irreversibly depressed in a time- and dose-dependent manner. These convergent findings point to the toxic effect of i.p. BHA on gut musculature with consequent impairment of intestinal transit.
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|Titolo:||Toxic injury to rat gut musculature following intraperitoneal administration of 2-t-butyl-4-methoxyphenol.|
|Citazione:||Sgaragli, G.P., Valoti, M., Fusi, F., Palmi, M., Mantovani, P., De Santi, M.m., et al. (1993). Toxic injury to rat gut musculature following intraperitoneal administration of 2-t-butyl-4-methoxyphenol. EUROPEAN JOURNAL OF PHARMACOLOGY, 248, 121-129.|
|Appare nelle tipologie:||1.1 Articolo in rivista|
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