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PubMedDate not supplied

Histochemical changes of the rat testis and epididymis after treatment of alpha-chlorohydrin-effects of a single low dose.

A histochemical study has been made of the localization and changes of lipids, carbohydrates, ATPase and 5'-nucleotidase in fresh and fixed frozen sections of testicular and epididymal components in the normal and alpha-chlorohydrin-treated rats. After treatment with a single low dose of alpha-chlorohydrin, the phospholipids are decreased with corresponding increase in triglycerides in both the testis and epididymis. Glycogen, ATPase and 5'-nucleotidase are also decreased after treatment with alpha-chlorohydrin. The physiological significance of these histochemical changes has been discussed.

Adenosine Triphosphatases↗
PubMed1979

Effect of sodium nitrite on the alpha-chlorohydrin-induced lesion of the testis--epididymis complexin the rat.

Administration of vasodilator, sodium nitrite (20 mg/kg body weight), 30 min before alpha-chlorohydrin treatment (90 mg/kg body weight) prevented the chlorohydrin-induced lesion in rat testis--epididymis complex. However, administration of vasodilator 90 min after alpha-chlorohydrin treatment did not prevent the chlorohydrin-induced lesion in the testis--epididymis complex. These observations suggest that the testicular vasculature is involved in drug action.

Animals↗
PubMed1979

Effect on gonadotrophin secretion of blockage of the ductuli efferentes in the normal and androgen-deprived rat.

Serum LH and FSH concentrations were measured in adult male rats. Blockage of the ductuli efferentes by surgical ligation or treatment with the anti-fertility drug alpha-chlorohydrin did not produce any changes in serum LH or androgen-dependent organ weights. Serum FSH in both groups was significantly raised by 4 days after treatment and remained so throughout most of the experimental period (42 days) but did not attain the values obtained in castrates. The gonadotrophin changes were accompanied by an initial increase in the weight and turgidity of the testes which then became flaccid and atrophied. These changes were similar but not identical after both treatments. Androgen secretion was impaired in adult rats treated with ethylene dimethane sulphonate; serum LH values were similar to those of 14-day castrates, and serum FSH was also elevated but not to the level found in the castrates. Ligation of the ductuli efferentes did not produce any further changes in concentrations of either hormone in spite of the retention of the testicular products within the testes as reflected by an increase in weight. The results are consistent with the view that changes in serum FSH after blockage of the ductuli efferentes are related to disturbances in the production of inhibin from the seminiferous epithelium rather than retention of inhibin with the testicular tubules.

Animals↗
PubMed1979

Agonistic properties of low doses of antifertility compounds in male rats.

Male Wistar Strain rats of known fertility were given subcutaneous dosage of three drugs, alpha-chlorohydrin, amino-alpha-chlorohydrin, and busulphan alone or in combination for a period of thirty days. Males were housed overnight with females at various times during the treatment and ninety days after cessation of treatment. There were significant differences in levels of glycerylphosphorylcholine in the epididymides of two treatment groups as well as differences in numbers of spermatozoa recovered from the reproductive tracts of female rats mated with males from four treatment groups. Treatment had no effect on the weights of the testes or sex accessory organs or sialic acid levels in the epididymis, fructose levels in dorso-lateral prostate and coagulating gland, or citric acid levels in seminal vesicle and ventral prostate of the treated males when compared to controls. The antifertility activity was probably mediated by an effect on epididymal spermatozoa and thereby subsequent change in sperm transport within the female genital tract.

Animals↗
PubMed1979

The metabolism of the soil fumigant 1,2-dibromo-3-chloropropane in the rat.

The soil fumigant 1,2-dibromo-3-chloropropane (I) undergoes hydrolysis in the rat to a series of epoxide metabolites. Alkylation of glutathione by these epoxides produces 2 urinary metabolites identified as the mercapturic acids VI (R=COCH3) and VII (R-COCH3). Hydrolysis of the epoxides produces the male antifertility agents alpha-chlorohydrin (IX, X-Cl) and alpha-bromohydrin (IX, X-Br) which are oxidatively metabolized to oxalic acid (XII), thus causing renal damage. These metabolic pathways can explain the toxic nature of the fumigant as a carcinogen, a male chemosterilant and as an agent causing kidney damage.

Animals↗
PubMed1978

Embryopathies due to spermatozoal impairment in Xenopus laevis.

An in vitro test system, involving gametes of Xenopus laevis has been used to study the effect of antifertility agents upon spermatozoa as manifest in developing embryos. Exposure to either the isomeric forms of dimethylmyleran, methyl methanesulphonate or gamma-radiation led to development of a range of embryopathies, whereas treatment with steroidal drugs or the rodent epididymal chemosterilants alpha-chlorohydrin and trimethylphosphate was compatible with production of apparently normal offspring.

Abnormalities, Drug-Induced↗
PubMed1979

Mutagenicity of halogenated and oxygenated three-carbon compounds.

Four structurally related three-carbon compounds, known for their antifertility activity in the male, and the brominated derivatives of two of these compounds were tested for mutagenic activity by the Salmonella typhimurium test of Ames et al. In the presence of strain TA-100, a base-pair substituion detector strain, 1,2-dibromo-3-chloropropane (DBCP), was the most active compound tested but required enzymatic conversion by 59 microsomal preparation to an active mutagen. Three of these compounds containing an epoxide group-epichlorohydrin, epibromohydrin, and glycidol-were highly active direct mutagens, not requiring 59 for activation, alpha-Chlorohydrin was the least active compound tested; alpha-bromohydrin was 40 times more active than its chlorinated analog. Epibromohydrin was only slightly more active than epichlorohydrin, but both were highly active. With both of the halogenated epoxides, 59 preparation caused a substantial decrease in mutagenic activity at every concentration tested. All six compounds showed dose-related responsiveness for the base-pair substitution detector strains used. However, they were relatively inactive against the frameshift detector strain of S. typhimurium, TA-98. Glycerol, propylene glycol, and n-propanol, which are also three-carbon compounds containing one or more hydroxy groups, were inactive when trested at high concentrations with strain TA-100.

Alcohols↗
PubMed1979

The metabolism of 3-amino-1-chloropropan-2-ol in relation to its antifertility activity in male rats.

1. The metabolism of 3-amino[36Cl]chloropropan-2-ol (III) was studied in male rats. Three urinary metabolites were isolated and identified as alpha-chlorohydrin (I), beta-chlorolactic acid (V) and oxalic acid (VI). Much of the administered aminochloropropanol was excreted unchanged in the urine; 63% within 72 h, 75% over 250 h. 2. Monoamine oxidase is capable of converting aminochloropropanol to beta-chlorolactaldehyde (IV) which, by processes of either reduction or oxidation, suggests that the metabolic pathway is IV leads to I and IV leads to V leads to VI. 3. As assessed by the diuretic activities of the isomers of aminochloropropanol, oxalate appears to be produced by the (+)-isomer but not by the (-)-isomer. A difference in metabolic rate or route of the isomers may account for their differing physiological activities. 4. (+)- and (-)-aminochloropropanol exhibited identical in vitro inhibitory activities on the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase and triosephosphate isomerase, and were substrates for monoamine oxidase to equivalent extents.

Animals↗
PubMed1976

Purification and properties of arylsulphatase A from rabbit testis.

Rabbit testis arylsulphatase A was purified 140-fold with a recovery of 20% from detergent extracts of an acetone-dried powder by using DE-52 cellulose column chromatography, gel filtration on Sephadex G-200 and preparative isoelectric focusing. The purified enzyme showed one major band with one minor contaminant on electrophoresis in a 7.5% (w/v) polyacrylamide gel at pH8.3. On sodiumdodecyl sulphate/polyacrylamidegel electrophoresis, a single major band was observed with minor contaminants. The final preparation of enzyme was free from general proteolytic, esterase, hyaluronidase, beta-glucuronidase and beta-galactosidase activities. Rabbit testicular arylsulphatase A exists as a dimer of mol.wt. 110000 at pH7.1. At pH5.0 the enzyme is a tetramer of mol.wt. 220000. Arylsulphatase A appears to consist of two identical subunits of mol.wt. 55000 each. The highly purified enzyme has pI4.6. The enzyme hydrolyses p-nitrocatechol sulphate with Km and Vmax, of 4.1 mM and 80nmol/min respectively, but has no activity toward p-nitrophenyl sulphate. The pH optimum of the enzyme varies with the incubation time. By applying Sephacex G-200 chromatography and preparative isoelectric focusing, one form of enzyme was obtained. The enzyme has properites common to arylsulphatase A of other sources with respect to the anomalous time-activity relationship, pI, inhibition by PO42-, SO32- and Ag+ ions and substrate affinity to p-nitrocatechol sulphate. However, the enzyme shows the temperature optimum of arylsulphatase B of other species.

Animals↗