Toxic injury to rat gut musculature following intraperitoneal administration of 2-t-butyl-4-methoxyphenol.
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.
Sgaragli
G P
GP
Istituto di Scienze Farmacologiche, Università degli Studi di Siena, Italy.
Valoti
M
M
Fusi
F
F
Palmi
M
M
Mantovani
P
P
De Santi
M M
MM
Lorenzini
L
L
Tosi
P
P
D000284:Administration, Oral; D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity; D002083:Butylated Hydroxyanisole / Q000008:administration & dosage / Q000633:toxicity*; D004121:Dimethyl Sulfoxide / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005775:Gastrula / Q000187:drug effects*; D007082:Ileum / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D007274:Injections, Intraperitoneal; D008297:Male; D008854:Microscopy, Electron; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D001555:Benzene Derivatives; D002083:Butylated Hydroxyanisole; C063841:tert-butylbenzene; D004121:Dimethyl Sulfoxide