Disease relevance of Glycerol alpha-monochlorohydrin

• An enzyme capable of dehalogenating vicinal haloalcohols to their corresponding epoxides was purified from the 3-chloro-1,2-propanediol-utilizing bacterium Arthrobacter sp. strain AD2 [1].
• To investigate the relationship between sperm motion parameters and fertilizing ability, a model was developed to assess both of these endpoints synchronously using a toxicant that inhibits sperm motion. alpha-Chlorohydrin (ACH) was administered daily for 4 days to male hamsters at 0, 33, 49, 66, and 83 mg/kg body weight [2].
• The antifertility activity and toxicity of alpha-chlorohydrin derivatives in male rats [3].
• At a dose of 5 mg/kg injected intraperitoneally each day for 14 days, only alpha-chlorohydrin produced complete infertility [3].
• The organisms E. coli, S. aureus, K. aerogenes, Pr. vulgaris and S. abortusovis were inhibited by 3-chloropropane-1,2-diol at high concentrations (ca 10,000 mug/ml) and Ps. aeruginosa was unaffected [4].

High impact information on Glycerol alpha-monochlorohydrin

• Identification of the biochemical lesion produced by alpha-chlorohydrin in spermatozoa [5].
• We present a simple in vivo model in which primary astrocyte loss is followed by microvascular damage, using the metabolic toxin 3-chloropropanediol (S-alpha-chlorohydrin) [6].
• Male Fisher F344 rats given systemic 3-chloropropanediol showed astrocytic loss in the inferior colliculus from 12-24 h until the lesion was repopulated 8-28 days later [7].
• Male Fisher F344 rats given 3-chloropropanediol show astrocytic damage and death at 4-24 h in symmetrical brainstem and midbrain nuclear lesions, while neurons show morphological changes at 24-48 h [6].
• Sperm maturation may be impaired by alpha-chlorohydrin, antiandrogens, or sulphasalazine, and sperm motility in the female genital tract can be inhibited by vaginal spermicides such as nonoxynol-9 and by propranolol [8].

Chemical compound and disease context of Glycerol alpha-monochlorohydrin

• Daily administration of 9 mg/kg alpha-chlorohydrin for 7--14 days and 24 mg/kg 6CDG for 14--21 days induced sterility in male rats and imparied the capacity of the cauda epididymal spermatozoa to initiate motility [9].
• In this study, we investigated the toxicity of alpha-chlorohydrin (alpha-CH) and m-dinitrobenzene (m-DNB) in an in vitro BBB model, the rat brain capillary endothelial cell line RBE4 [10].
• Comparative testicular toxicities of two isomers of dichloropropanol, 2,3-dichloro-1-propanol, and 1,3-dichloro-2-propanol, and their metabolites alpha-chlorohydrin and epichlorohydrin, and the potent testicular toxicant 1,2-dibromo-3-chloropropane [11].
• The reproductive toxicity of glycidol was believed to result from its conversion to alpha-chlorohydrin by the action of HCl in the stomach [12].

Biological context of Glycerol alpha-monochlorohydrin

• Mode of action of alpha-chlorohydrin as a male anti-fertility agent. Inhibition of the metabolism of ram spermatozoa by alpha-chlorohydrin and location of block in glycolysis [13].
• The dehalogenase had a broad pH optimum at about 8.5 and a temperature optimum of 50 degrees C. The enzyme followed Michaelis-Menten kinetics, and the Km values for 1,3-dichloro-2-propanol and 3-chloro-1,2-propanediol were 8.5 and 48 mM, respectively [1].
• The fertilizing ability of epididymal spermatozoa from rats and mice treated for 3 or 4 or 9 or 10 days with various doses of alpha-chlorohydrin was tested in vitro, and in vivo by intrauterine insemination [14].
• A method based on capillary electrophoresis with electrochemical detection (CE-ED) to calculate the rate constants and activation energy of 3-chloro-1,2-propanediol (3-MCPD) hydrolysis was described [15].
• Futile substrate cycles in the glycolytic pathway of boar and rat spermatozoa and the effect of alpha-chlorohydrin [16].

Anatomical context of Glycerol alpha-monochlorohydrin

• Studies on the rat epididymal blood vessels following alpha-chlorohydrin administration [17].
• Effects of alpha-chlorohydrin on the testes and epididymides of dog: a preliminary study [18].
• Proceedings: Decrease in the glycerylphosphorylcholine content of the epididymis after injecting alpha-chlorohydrin into rats [19].
• The male antifertility agents alpha chlorohydrin, 5-thio-D-glucose, and 6-chloro-6-deoxy-D-glucose interfere with sugar transport across the epithelium of the rat caput epididymidis [20].
• The rate of entry of alpha-chlorohydrin into rat rete testis fluid has been studied using the 14-C and 36-Cl-labelled compounds [21].

Associations of Glycerol alpha-monochlorohydrin with other chemical compounds

• The entry of alpha-chlorohydrin into body fluids of male rats and its effect upon the incorporation of glycerol into lipids [21].
• Although 0.05 or 5.56mM glucose plus alpha-chlorohydrin stimulated sperm motility, they did not further stimulate the increase in cAMP after 30 s of incubation [22].
• The total cholesterol per gram of testis was increased significantly after alpha-chlorohydrin administration [18].
• It is concluded that the S enantiomer is responsible for both the inhibition of sperm glycolysis and the reduction in fertility caused by the racemic mixture of alpha-chlorohydrin [23].
• The vicinal chloroalcohols 1,3-dichloro-2-propanol (DC2P), 3-chloro-1,2-propanediol (3CPD) and 2-chloro-1,3-propanediol (2CPD) are not genotoxic in vivo in the wing spot test of Drosophila melanogaster [24].

Gene context of Glycerol alpha-monochlorohydrin

• A similar pattern of inhibition was seen in spermatozoa from hamsters given alpha-chlorohydrin (50 or 100 mg/kg/day) for 10 days. alpha-Chlorohydrin (66 mg/kg/day s.c.) for 10 days inhibited GAPDH in spermatozoa from the caput or corpus epididymidis of the guinea-pig by less than 20% but decreased GAPDH activity by almost 90% in the cauda region [25].
• Effect of sodium nitrite on the alpha-chlorohydrin-induced lesion of the testis--epididymis complexin the rat [26].
• The chloropropanediol diesters were found to be composed of molecular species containing C10-C18 fatty acids and corresponded closely in carbon number to those calculated for the long chain sn-1,2-diacylglycerol moieties of goat milk triacylglycerols [27].
• Qualitative and quantitative changes of acetylcholinesterase in the central nervous system of mice during low and high dose treatment of alpha-chlorohydrin [28].
• Its effect on the concentrations of glycolytic intermediates suggests that the pathway is inhibited at the glyceraldehyde 3-phosphate dehydrogenase reaction. alpha-Chlorohydrin is oxidized by boar liver homogenates via 3-chlorolactaldehyde to 3-chlorolactate [29].

Analytical, diagnostic and therapeutic context of Glycerol alpha-monochlorohydrin

• Furthermore, after treatment with alpha-chlorohydrin (aCH) as a male antifertility agent affecting rat epididymal sperm motion, sperm velocities in HAA rats were significantly reduced to levels similar to those in untreated LAA rats [30].
• Gas-liquid chromatography of 3-chloropropanediol [31].
• Determination of rate constants and activation energy of 3-chloro-1,2-propanediol hydrolysis by capillary electrophoresis with electrochemical detection [15].
• Both esters were found to be of comparable molar potency to alpha-chlorohydrin in inducing temporary infertility following daily oral administration [32].
• With alpha-Chlorohydrine, sperm count was not affected and the results of the histopathological examination were equivocal [33].

References