Distribution and covalent interactions of [1-14C]acrylonitrile in the rat.

The tissue distribution, elimination and covalent binding of [1-14C]-acrylonitrile (VCN) have been investigated in the rat. Rats, given an oral dose of 46.5 mg/kg (0.5 LD50) VCN, excreted 40% of the 14C in urine, 2% in feces, 9% in expired air as 14CO2, 0.5% as H14CN and 4.8% as unchanged VCN in 24 h. Bile flow increased 3 times after the administration of VCN and over a period of 6 h, 27% of the 14C was recovered in bile. The red blood cells retained significant amounts of radioactivity for more than 10 days after treatment, whereas the 14C activity declined sharply in plasma. Initially, the highest levels of radioactivity were found in the stomach and stomach content followed by the intestine. In liver, kidney, brain, spleen, adrenal, lung and heart tissues the radioactivity of the acid soluble fractions declined while covalent binding to macromolecules remained unchanged. In subcellular fractions of liver, kidney, spleen, brain, lung, and heart, 20-40% of the total radioactivity was bound to nuclear, mitochondrial and microsomal fractions whereas in cytosol only 6-14% was bound over a period of 6 h.

Synthesis of some indane derivatives of central muscle relaxant and anticonvulsant profiles.

A series of 2,2-bis(hydroxymethyl)indane derivatives 1a-f, 2a-e and 3a-f were synthesized to investigate their central muscle relaxant and anticonvulsant activities. The synthesized compounds 1a-f, 2a-e and 3a-f were found to be devoid of central muscle relaxant activity using meprobamate (100 mg/kg) as a reference standard. However, they showed remarkable anticonvulsant properties in a dose of 80 mg/kg (s.c.) compared with diphenylhydantoin sodium (80 mg/kg) as a reference standard.

Synthesis of some N-substituted indole derivatives and their biological activities.

Acylation of 2,3-diphenyl-5-methoxy-indole using ethyl chloroformate or chloroacetyl chloride in dimethylformamide and sodium hydride yielded the N-substituted derivatives 1 and 2, respectively. While Friedel-Crafts acylation using chloroacetyl chloride afforded di-4,6-chloroacetyl derivative 3, the reaction of the N-chloroacetyl derivative 2 with amines, hydrazines, urea, semicarbazide hydrochloride, thiophenol, benzimidazole-2-thiol, thiosemicarbazide, 2-mercaptoethanol and thioglycolic acid was studied. Several of the compounds were tested for their effect on arterial blood pressure, antiinflammatory and ulcerogenic activities.

Toxicological study of the different organs of Corchorus olitorius L. plant with special reference to their cardiac glycosides content.

The acute toxicity of the alcoholic extracts of seeds, roots stems and leaves of the fully mature Corchorus olitorius L. plant was determined in mice by intraperitoneal injection. The cardiac glycosides content of each extract was estimated and the correlation between the two investigated parameters was established. The chronic toxicity of the alcoholic extract of the seeds was determined in term of its haematological and symptomatical effects on mice upon intraperitoneal injection for a period of two months.

Comparative toxicokinetics of 2,3-14C-and 1-14C-acrylonitrile in the rat.

The tissue distribution, elimination and covalent binding of 2,3-14C-and 1-14C-acrylonitrile (VCN) were studies in male Sprague-Dawley rats given an oral dose of 46.5 mg kg-1. Exhalation of unchanged VCN, 14CO2 and H14CN was monitored at selected intervals. Only 5% of the total dose administered was recovered was unchanged VCN. Rate given 2,3-14C-VCN exhaled only 2% of 14C activity was 14CO2 and none was recovered as H14CN, whereas rats given 1-14C-VCN exhaled about 12% of 14C activity as 14CO2 and 0.5% as H14CN. In the initial 24 h, 40% of radioactivity from 1-14C-VCN appeared in urine, while 60% was recovered in the urine of rats given 2,3-14C-VCN. The red blood cells retained significant amounts of radioactivity from both the compounds for more than 10 days after administration, whereas the 14C activity in plasma declined sharply. The highest level of radioactivity from both compounds was recovered in the gastrointestinal tract. In liver, kidney, brain, spleen, adrenal, lung and heart tissues the unbound percent radioactivity decreased, while irreversible percent covalent binding to macromolecules in relation to total increased concomitantly. Subcellular fractionation of the tissues showed that most of the covalently bound radioactivity was distributed in non-cytosolic fractions. As compared to 1-14C-VCN administered animals, the percentage of covalent binding of 2,3-14C-VCN was significantly higher even 72 h after dosing. The relationship between covalent binding and acrylonitrile toxicity is discussed.