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At least 19 recordsLinked to original sources

PubMed2001

Effects of beta-aminopropionitrile on equine tendon metabolism in vitro and on effects of insulin-like growth factor-I on matrix production by equine tenocytes.

OBJECTIVE: To investigate effects of beta-aminopropionitrile and a combination of insulin-like growth factor (IGF)-I and beta-aminopropionitrile on metabolism of equine tendon fibroblasts. SAMPLE POPULATION: Flexor tendon explants from 3 horses. PROCEDURE: Explants received 1 of 4 treatments (control, IGF-I, beta-aminopropionitrile, and IGF-I/beta-aminopropionitrile) for 10 days, and message expression for collagen types I and III was assessed by use of in situ hybridization. Histologic findings, new protein production, and quantitative determinations of glycosaminoglycan, DNA, and de novo collagen synthesis were made. RESULTS: Insulin-like growth factor-I stimulated an anabolic response in tendon. Collagen synthesis and glycosaminoglycan and DNA content of explants were all increased. Beta-aminopropionitrile significantly suppressed collagen synthesis, which was not ameliorated by concurrent IGF-I treatment. Beta-aminopropionitrile caused alterations in cell morphology characterized by large round cells with eccentric nuclei and decreased density of collagen fibers. Protein production and collagen type-III mRNA expression were reduced in these cells. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with beta-aminopropionitrile resulted in decreased production of protein and collagen synthesis, which could be expected to suppress tendon healing. The negative effects of beta-aminopropionitrile could not be abrogated by addition of IGF-I to the medium. Treatment resulted in alterations in cell morphology and matrix consistency, which could further delay tendon healing. Beta-aminopropionitrile may impair tendon healing at a cellular level by decreasing collagen production or increasing rate of degradation of existing matrix. Because of reduced crosslinking during beta-aminopropionitrile treatment, in combination with transiently decreased tensile strength, alterations in collagen content and structure may weaken the healing tendon.

Aminopropionitrile↗

PubMed1999

Integrative cartilage repair: inhibition by beta-aminopropionitrile.

The effects of beta-aminopropionitrile, a known inhibitor of lysyl oxidase, on the extractability of newly synthesized collagen and integrative cartilage repair were determined in explant cultures of adult bovine articular cartilage. Dose-escalation studies indicated that treatment of cartilage explants for 6 days with beta-aminopropionitrile caused a dose-dependent inhibition of proteoglycan synthesis ([35S]sulfate incorporation) with a 50% inhibition at 2.2 mM. However, 0.25 mM beta-aminopropionitrile had no detectable effect on proteoglycan synthesis and was thus used for subsequent experiments. Treatment of cartilage with beta-aminopropionitrile for 14 days increased the extractability of newly synthesized collagen with 4 M guanidine-HCl while having little effect on proteoglycan synthesis, proteoglycan deposition, collagen synthesis (formation of [3H]hydroxyproline after labeling with [3H]proline), collagen deposition, or cartilage cellularity (DNA content). In untreated cultures, the percentage of radiolabeled collagen ([3H]hydroxyproline) that was extractable after 1 day of radiolabeling, 6 days of radiolabeling, or 6 days of label and 6 days of chase decreased from 81 to 25 and 9%, respectively. In beta-aminopropionitrile-treated cultures, the extractability was relatively higher (96, 62, and 47%, respectively). Treatment with beta-aminopropionitrile after radiolabeling with [14C]lysine also significantly inhibited the formation of the reducible crosslink [14C]dihydroxylysinonorleucine without affecting the overall deposition in cartilage of [14C]lysine and [14C]hydroxylysine. In functional repair studies, treatment with beta-aminopropionitrile caused an almost complete inhibition of integration between pairs of cartilage explants maintained in apposition for 2 weeks. These results indicate that beta-aminopropionitrile blocks the formation of collagen crosslinks in cartilage explants and suggest that such crosslinks are critical to integrative cartilage repair.

Aminopropionitrile↗

PubMed1984

Effects of topical treatment with beta-aminopropionitrile after radial keratotomy in the rabbit.

This study assessed the effect of beta-aminopropionitrile treatment on the long-term curvature and compliance of corneal tissue subjected to radial keratotomy (RK). beta-Aminopropionitrile is known to inhibit cross-linking of collagen and is expected to enhance the flexibility of scar tissue, thereby reducing wound contracture and regression after RK. Seventeen adult New Zealand rabbits, weighing about 4.5 kg each, underwent RK in both eyes (eight incisions, 90% deep, 3-mm pupillary zone). Their mean preoperative corneal curvature was 44.25 diopters (+/- 0.32D at 95% confidence level). Nine of the rabbits were treated topically with beta-aminopropionitrile ointment (33 weight % in petroleum three times daily), while the control group received the petrolatum base only. The remainder of the animals received bland petrolatum gel as a control. The animals were given periodic keratometric examinations and were killed after six to eight weeks. At that time, the beta-aminopropionitrile group showed a mean reduction of 1.85 +/- 0.13 D in corneal curvature, compared with 1.18 +/- 0.08 D in the control group. The compliance and strength of the corneas were measured in vitro immediately after death. In the pressure range from 10 to 40 mm Hg, the beta-aminopropionitrile-treated corneas changed in curvature by an average of 1.4 D as compared with 0.5-D flattening for the controls. These results indicate the effectiveness of beta-aminopropionitrile treatment in enhancing longterm compliance and reducing refractive regression after RK.

Administration, Topical↗

PubMed1973

Alterations in glycosaminoglycan metabolism in beta-aminopropionitrile-treated chick embryos.

1. Na(2) (35)SO(4), [1-(14)C]glucosamine and [1-(14)C]acetate were used as precursors of the sulphated glycosaminoglycans to study the biochemical effect of beta-aminopropionitrile in chick embryos. The incorporation of all three precursors was decreased in the treated embryos between days 7 and 10 of embryonic development. No inhibition of incorporation of these precursors occurred between days 16 and 20 of embryonic development at the dosages of beta-aminopropionitrile used. 2. beta-Aminopropionitrile treatment also decreased the amount of N-acetylhexosamines in the chick embryo and decreased the percentage of the hexosamine esterified by nucleotides. Respiration was decreased by homogenates prepared from treated embryos. Likewise, UDP-xylosyl- and UDP-galactosyl-transferase activities were decreased in treated embryos and cartilage from embryos and growing chicks. 3. The data suggest that beta-aminopropionitrile, in addition to the known lathyrogenic activity, either is or gives rise to a potent metabolic poison that interferes with basic cellular metabolism. The results are consistent with a decreased rate of ATP generation as an explanation for the decrease in glycosaminoglycan synthesis.

Acetates↗

PubMed1984

Elastin fiber-associated glycosaminoglycans in beta-aminopropionitrile-induced lathyrism.

Ruthenium red and toluidine blue O precipitates were described associated with lathyritic elastic fibers in aortas of chickens treated with beta-aminopropionitrile fumarate (I. Pasquali-Ronchetti, C. Fornieri, I. Castellani, G. M. Bressan, and D. Volpin (1981). Alterations of the connective tissue components induced by beta-aminopropionitrile. Exp. Mol. Pathol. 35, 42-56). In this report evidence is given that these precipitates reveal the presence of proteoglycans, as they are completely removed by 5 M guanidine-HCl incubation and by specific enzymatic digestions. In particular, proteoglycans associated with the poorly cross-linked lathyritic elastin can be removed by testicular hyaluronidase, chondroitinase ABC, heparitinase, and nitrous acid treatments, whereas they are rather resistant to streptococcal hyaluronidase and chondroitinase AC. On the contrary, proteoglycans of the matrix or associated with collagen fibers are particularly sensitive to these latter enzymatic treatments. The conclusion is reached that glycosaminoglycans associated with beta-aminopropionitrile-induced lathyritic elastin (i) are different from those of the matrix or associated with collagen, and (ii) include mainly dermatan and heparan sulfates.

Aminopropionitrile↗

PubMed1997

The Cantrell-sequence: a result of maternal exposure to aminopropionitriles?

The characteristic features of the Cantrell-sequence--anterior thoraco-abdominal wall defect with ectopia cordis and diaphragm, sternum, pericardium, and heart defects--have been observed in animals following maternal administration of beta-aminopropionitrile, a toxic amino-acid derivative. We report on an unusual case of the Cantrell-sequence in a premature infant with associated dysmelia, aplasia of the right kidney, cerebellar hypoplasia and circumscribed aplasia of the cutis, which has not been reported previously. Maternal history suggested an occupational exposure to aminopropionitriles prior to pregnancy. Prenatal ultrasound, differential diagnosis, perinatal management, and the teratogenic role of aminopropionitriles in this rare genetic disorder are discussed.

Abnormalities, Multiple↗

PubMed1991

Possible biotransformation mechanism of 3-aminopropionitrile by means of free radicals.

The possible role of free radicals in the transformation of 3-aminopropionitrile giving rise to the liberation of cyanide was studied. Rat liver homogenates were cellularly fractionated. It was confirmed that the transformation occurred mainly in the microsomal fraction. The different isozyme forms of cytochrome P-450 were then partially purified and their velocity and affinity constants determined. It could be deduced that the cyanide-forming activity was mainly due to the LM3C cytochrome form. Dimethylsulfoxide was a potent competitive transformation inhibitor while mannitol was a moderate one. An OH radical generator inorganic system was also shown to liberate cyanide from 3-aminopropionitrile. In view of these results, a transformation mechanism of 3-aminopropionitrile by means of OH free radicals is suggested with the formation of cyanide anion in a cell-free organic system as well as in the microsomal fraction of rat liver.

Aminopropionitrile↗

PubMed1995

The effect of beta-aminopropionitrile on bleomycin-induced lung injury in rats.

The effect of beta-aminopropionitrile on collagen cross-links, lysyl oxidase and prolyl hydroxylase and particular collagen type content in rat lungs after bleomycin treatment was investigated. It was stated, that beta-aminopropionitrile significantly diminishes elevated dihydroxylysinonorleucine to hydroxylysinonorleucine ratio, prevented increase of lysyl oxidase activity and increase in type I collagen content in the lungs. It is suggested, that beta-aminopropionitrile may be useful in the treatment of lung fibrosis.

Aminopropionitrile↗

PubMed1977

Effect of beta-aminopropionitrile on bone mechanical properties.

In vivo beta-aminopropionitrile treatment caused significant changes in the mechanical properties of rat femora. In femora treated with beta-aminopropinitrile as compared with controls, there was a 44 per cent decrease in bone stiffness and a 47 per cent increase in bone deformation to failure. Bone ash was decreased 5 per cent in the treated group. It is likely that the decrease in bone ash was secondary to impaired intermolecular bone-collagen cross-linking, which is a well established consequence of treatment with beta-aminopropionitrile. Thus, beta-aminopropionitrile influences bone mechanical properties directly by impairing collagen cross-linking and indirectly by altering bone-matrix mineralization.

Aminopropionitrile↗

PubMed1977

Congenital kyphoscoliosis and spinal cord lesion produced in the rat by beta-aminopropionitrile.

Pregnant rats received the lathyrogen beta-aminopropionitrile (1,500 mg/kg) intraperitoneally on day 16 (plug day = 0 day). Kyphoscoliosis was produced in a high incidence in the fetuses at the level of the upper thoracic spine as early as 24 hours after treatment. Although most of the affected newborns died within two weeks, survivors were studied until 20 weeks after birth. Survivors developed paraplegia in consequence of kyphoscoliosis. Both spinal deformity and motor disturbance were progressive. Biochemical and electron microscopic observations suggested that beta-aminopropionitrile treatment resulted in an inhibition of collagen formation in the spinal column and surrounding longitudinal ligaments of the fetuses six hours after the treatment. In addition, electron micrographs of vertebral bodies showed a decrease of proteoglycan granules in the extracellular matrix. Therefore, rupture and collapse of weakened ligaments and vertebral bodies might result in severe spinal deformity and spinal cord lesion.

Abnormalities, Drug-Induced↗

PubMed1976

Influence of D-penicillamine and beta-aminopropionitril on the metamorphosis of Rana temporaria.

Tadpoles of Rana temporaria (size 5-7 mm) were kept in solutions of D-penicillamine (DPA), beta-aminopropionitril (betaAPN), and L-thyroxine at different concentrations for 18 days. The influence of the substances on metamorphosis was investigated. In low concentrations (1 or 10 mg/100 ml) D-penicillamine accelerates the process of metamorphosis. At these concentrations investigated skeletal malformations could not be observed. A content of 100 mg of DPA/100 ml is toxic. After 8 days of exposure only 4 of the 15 test animals had survived. In all concentrations investigated, beta-aminopropionitril has a toxic action. In low concentration (1 mg/100 ml) deformities are found which could be described as bending of the femur and twisting of the whole hind limb. The animals are non-viable, they die shortly after termination of metamorphosis. Higher concentrations (10 or 100 mg/100 ml) are lethal within the first 10 days. L-thyroxine (0.01 mg/100 ml) shows the wellknown metamorphosis-accelerating effect.

Aminopropionitrile↗

PubMed1985

The control of peritendinous adhesions using topical beta-aminopropionitrile base.

The Lindsay chicken foot tendon model was utilized to test the effect of topically applied beta-aminopropionitrile base upon the tensile strength of peritendinous adhesions following tenolysis of a scarified flexor tendon. The agent reduced by one-third the force required to effect tendon gliding and flexion of the joints in the involved digit. The results show that topical beta-aminopropionitrile is effective in the control of peritendinous adhesions and, therefore, achieves sufficient depth of penetration topically to affect the peritendinous location. No adverse effects of the topically applied agent were demonstrated. The principle of topical therapeutics that may have significant benefits to patients with tendon injuries is demonstrated.

Administration, Topical↗

PubMed1990

Allylamine and beta-aminopropionitrile-induced vascular injury: an in vivo and in vitro study.

Toxic cardiovascular effects of allylamine and beta-aminopropionitrile were studied in adult male Sprague-Dawley rats given allylamine alone (AA), 100 mg/kg/day, beta-aminopropionitrile alone (beta APN), 1 g/kg/day, or both chemicals (AA + beta APN) by gavage. Rats were given a total of 10 doses in 11 days. Rats given AA + beta APN showed extensive smooth muscle cell necrosis of the aortic media not seen when either toxin was given alone. Lingual artery lesions in the form of small intracellular eosinophilic globules were seen in animals given AA and AA + beta APN treatments, but were more numerous and larger in the latter group by morphometric analysis (p less than 0.03). Myocardial necrosis was much less severe in the AA + beta APN treatment group than in rats given only AA. A long-term follow-up (47 and 180 days) after the AA + beta APN protocol above showed that rats had persistent aortic medial necrosis with striking intimal cartilaginous metaplasia. Cultured porcine aortic smooth muscle cells exposed in vitro to combined AA and beta APN showed markedly decreased viability and increased cell injury when compared to cells exposed to only one toxin, thus supporting the synergistic toxic effect seen in vivo. Our studies show a synergistic necrotizing effect of AA and beta APN on aortic vascular smooth muscle cells. A hypothesis concerning these compounds' effects on vascular amine oxidases is made to explain this toxic synergism. Synergistic toxic interactions may be important in other forms of vascular injury.

Allylamine↗

PubMed1993

Joint action of benzoic hydrazide and beta-aminopropionitrile on Xenopus embryo development.

Binary mixtures of the osteolathyrogens benzoic hydrazide and beta-aminopropionitrile were tested to determine the joint action for these chemicals, by evaluating induction of malformation and osteolathyrism in developing frog embryos. Exposures, starting with late-blastula stage embryos, were for 96-h with solution renewal every 24-h. Five treatments were examined, each chemical alone (i.e., 1:0 and 0:1 solutions) and three mixtures (i.e., 3:1, 1:1, and 1:3). Following exposure, embryos were evaluated grossly and the incidences of all types of malformations and osteolathyrogenic lesions were determined. Toxic unit analysis and isobole diagrams indicated these chemicals were concentration additive in inducing malformations and osteolathyrism. Therefore, benzoic hydrazide and beta-aminopropionitrile induce osteolathyrism, in Xenopus embryos, in a similar manner.

Aminopropionitrile↗

PubMed1983

Topical beta-aminopropionitrile in the treatment of Peyronie's disease.

We treated 9 patients with Peyronie's disease for 1 to 8 years in duration with a 4-week course of beta-aminopropionitrile free base as the pure liquid. The drug was applied topically to the plaques twice daily. Patients were followed with ultrasound imaging of the plaques and saline inflations of the corpora cavernosa with photographic documentation of the deformity. No significant adverse effect was noted. Three patients experienced a subjective response but did not demonstrate objective change on the aforementioned studies. It was concluded that topical beta-aminopropionitrile was not effective in reversing the deformity of Peyronie's disease. Further investigation into specific anti-collagen drugs for the treatment of this condition may be warranted.

Administration, Topical↗

PubMed1977

Reduction of blood pressure and vascular collagen in hypertensive rats by beta-aminopropionitrile.

beta-Aminopropionitrile, a specific inhibitor of lysyl oxidase prevented the rise in blood pressure induced by deoxycorticosterone-salt in rats. In addition, after the onset of hypertension, administration of beta-aminopropionitrile lowered the blood pressure. Concomitant with the lowering of blood pressure, there was a reduction in the more highly crosslinked form of vascular collagen. These findings would indicate that increases in vascular connective tissue are not only sequelae of hypertension, but may also contribute to the maintenance of elevated blood pressure.

Amino Acid Oxidoreductases↗

PubMed1991

Role of monoamine oxidase in aminopropionitrile-induced neurotoxicity.

Oxidation of aminopropionitriles was measured in vitro with both rat liver mitochondria and bovine plasma monoamine oxidase (MAO). The nonneurotoxic aminonitrile beta-aminopropionitrile (BAPN) was oxidized at a significantly higher rate (p less than .05) than either of the neurotoxic aminonitriles tested; 3,3'-iminodipropionitrile (IDPN) and 3,3'-dimethylaminopropionitrile (DMAPN). DMAPN was a poor substrate for both mitochondrial and plasma MAO. None of the aminonitriles tested were found to inhibit MAO activity in rat brain or liver in vivo. Inhibition of MAO activity with pargyline in vivo did not affect the pattern of IDPN- or DMAPN-induced toxicity. These results suggest that monoamine oxidase is not involved in aminonitrile-induced neurotoxicity.

Aminopropionitrile↗

PubMed1992

In vitro and in vivo inhibition of lysyl oxidase by aminopropionitriles.

Inhibition of lysyl oxidase (protein-lysine 6-oxidase, EC 1.4.3.13) decreases the rate of collagen and elastin cross-link formation and produces osteolathyrism in animals. Organic nitriles, including beta-aminopropionitrile (BAPN), have been shown to irreversibly inhibit lysyl oxidase in vitro. Both BAPN and 3,3'-iminodipropionitrile (IDPN) have been shown to produce osteolathyric changes when administered to animals. To date compounds that have been reported to inhibit this enzyme possess a primary amine functional group. In this study a series of primary and substituted aminopropionitriles was studied for their ability to inhibit lysyl oxidase activity both in vitro and in vivo. Our results show that of the compounds tested, BAPN was the most potent inhibitor of the enzyme. Reversible inhibition of lysyl oxidase in vitro was found with two secondary aminonitriles, IDPN and monomethylaminopropionitrile (MMAPN). There was no inhibition of enzyme activity associated with the tertiary compound 3,3'-dimethylaminopropionitrile (DMAPN) or propionitrile, a compound lacking an amine functional group. IDPN was found to produce a slight irreversible inhibition of the enzyme both in vitro and in vivo. Pretreatment of rats with pargyline, an inhibitor of monoamine oxidase, was found to increase the inhibitory potential of BAPN (p < or = .1). Pargyline pretreatment did not alter the inhibitory potential for any of the other aminonitriles tested. These results suggest that the presence of a primary amino functional group is not a strict requirement for inhibition of lysyl oxidase. In addition, reversible and irreversible mechanisms of inhibition may be involved in the production of osteolathyric changes associated with IDPN exposure.

Aminopropionitrile↗