Pharmacokinetic analysis of beta-aminopropionitrile in rabbits.

beta-Aminopropionitrile (beta APN), inhibits the activity of lysyl oxidase, an important enzyme for the post-translational formation of inter- and intramolecular covalent cross-linking between the connective tissue proteins, collagen and elastin. We became interested in the possible use of this compound as a therapeutic agent in the so-called human collagen diseases. beta APN's action mechanism is known, but its pharmacokinetics in rabbits have not yet been determined. The present study defined the kinetic parameters of beta APN in rabbits, after oral or intravenous (iv) administration. The HPLC technique was recently modified using OPA (ortho-phthalaldehyde) as the derivative agent. beta APN plasma concentration vs time following the iv administration of 200 mg/kg was best described by the biexponential equation C = 92.43.e(-0.0728 t) + 61.78.e(-0.0088 t) (t1/2 beta = 78.73 +/- 5.19 min; Vc = 1.29 +/- 0.04 L.kg-1). After oral administration, beta APN followed a zero-order absorption pattern (Ko = 3.02 +/- 0.34 mg.kg-1.min-1), which means that the beta APN reached the blood very quickly.

"In vitro" effects of methyl-mercury on the nervous system: a neurotoxicologic study.

Many of the currently prevailing toxicologic problems are due to the use of organic mercurial compounds in pesticides and fungicides. During recent years, environmental pollution has originated from the incorrect use of these organometals. Methyl-mercury (Me-Hg) is absorbed quickly from the gastrointestinal tract and is distributed to most tissues. The most important effect of Me-Hg is on the nervous tissue and is more relevant in the fetal brain. We were interested in assessing the neurotoxic effects of Me-Hg on the central and peripheral nervous system. Neuronal cells cultures from 14-day-old fetal Wistar rats and ciliary ganglion cells cultures from 8-day-old chick embryos were used. Various Me-Hg concentrations (10(-3) M to 10(-8) M) were added to these cultures after 36 hr to study the morphologic changes. At 10(-3) M and 10(-4) M concentrations, cellular degeneration and death in the central nervous system (CNS) were noted. At 10(-5) M concentrations, axonal and nerve fibers degeneration, loss of synapsis, and inhibition in the cellular development in CNS were seen; regroupment and destruction in the peripheral nervous system (PNS) was noted. Finally, at 10(-6) M and 10(-7) M concentrations, there were hardly any modifications in the CNS, whereas only the nervous processes were affected in the PNS.

Ethylene glycol action on neurons and its cholinomimetic effects.

Ethylene glycol (EG) is the most representative of the glycols. It is a compound used as painting and plastic solvent, as antifreeze, and in dyes and synthetic fibers. It may also appear as a wine pollutant. Due to these various uses and conditions, EG can produce intoxication in men and animals. The pathologic effects are due to its metabolism resulting in the formation of oxalic and glycolic acids which are eliminated through the kidney causing renal failure. The toxic effects on the nervous system are not well known. In some circumstances, convulsions may occur. To study the neurotoxic effects of EG, we used cultures of nerve cells from Wistar rat embryos which we exposed to EG in doses between 10(-4) M and 10(-8) M. The changes in neurons consisted of neuronal degeneration, decrease in number of AChE+ cells, and reactive cellular grouping. The median inhibitory concentration (IC50) was 2.06 x 10(-7) M.