Natural products
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NATURAL PRODUCTS 3338. More on congeners and alcohol metabolism
to the formation of calculi in the kidney and urinary bladder {Cited in F.C.T. 1969, 7, 395). Accordingly Auty, R. M. & Branch, R. A. (1977)" Pharmacokinetics the rate at which dietary oxalate is absorbed, to augand pharmacodynamics of ethanol, whiskey, and'eth- ment the body burden of endogenous oxalic acid (see below), is also significant. Isolated intestinal segments anol with n-propyl, n-butyl, and iso-amyl alcohols. of the jejunum, ileum and colon of rats were examined Clin. Pharmac. Ther. 22, 242. at intervals from 5 to 60 min after intraluminal injecCongeners present in alcoholic beverages may tion of t'C-labelled oxalate solution in saline. The affect ethanol elimination, but the significance of any initial absorption of oxalat.e was rapid, at 6.5%/rain, °/ " Absorpsuch effect for the moderate drinker is uncertain but decreased after 5rain to about 0-6,,,/ram. (Cited in F.C.T. 1977, 15, 653). A study of the in- tion was greatest in the jejunum and least in the fluence of the three predominant congeners, ~t-pro- colon. A rapid initial influx of water into the gut panol, n-butanol and isoamyl alcohol, on the pharma- lumen may have been a response to the "noxious cokinetics of ethanol in six normal men, all moderate effect" of oxalate on tissue, since the experimental challenge solutions were nearly iso-osmolar with drinkers, throws some light on this problem. In a randomized double-blind, crossover trial, each plasma. The abrupt reduction of oxalate absorption drink (ethanol alone, whiskey or a mixture of ethanol after about 5 rain suggests that oxalate may inhibit with the three higher alcohols) was equivalent to 1 g its own absorption. Oxhlate absorption was also studied with solutions ethanol/kg body weight, diluted to 600ml with orange juice and consumed at a constant rate over of [~4C]oxalate containing a 4 mM 'concentration of 20 rain. Blood samples were taken and reaction times calcium chloride, magnesium chloride or sodium oxaand electroencephalograms (EEGs) were recorded late. No difference in the apparent rate of [t4C'[oxa before the dose, at 20-min intervals after the dose late transfer was produced by addition of these salts, for 2 hr and then at 30-rain intervals for 3 hr. All three except in the jejunum, where absorption was accelerdrinks produced similar plasma-ethanol concen- ated by magnesium chloride. It is calculated that at o/ of a challenge dose of oxalate should be trations eventually, but the peak was reached more least 8 6,,, slowly after whiskey ingestion (mean 83 min) than absorbed from the small bowel during normal food after ethanol alone (63min), and was even more transit. Since the addition of magnesium failed to dedelayed (97 min) after the ethanol-higher alcohol mix- crease [laC]oxalate absorption in the rat model, it ture, in which the concentration of the congeners was is unlikely that supplementation of the diet with magabout twice that in the whiskey. The terminal phase nesium in attempts to alleviate or prevent the formaof ethanol elimination was consistent with exponen- tion of calcium oxalate calculi can be justified on the" tial decay in all the studies, the half-life being longer grounds that it reduces oxalate absorption; any effecafter the ethanol-higher alcohol mixture than after tive contribution of magnesium to the treatment of ethanol or whiskey. Reaction time was prolonged by oxalate stone disease in man seems to require some each treatment, reaching a peak after about 2 hr and other explanation. returning to normal within 5 hr, but deterioration in performance 2hr after whiskey was less than that 3340. Vitamin C and oxalate stones after the ethanol-higher alcohol mixture than after ethanol or whiskey. Reaction time was prolonged by Du Bruyn, D. B., De Klerk, W. A. & Liebenberg, anol concentrations when data for the full 5-hr period N.v.d.W. (1977). High dietary ascorbic acid levels and after alcohol administration were considered, the in- oxalate crystallization in soft tissues of baboons. S. crease in reaction time correlated positively with plas- Aft.. reed. J. 52, 861. ma-ethanol concentration during the linear phase of Oxalic acid is one of the end-products of ascorbic ethanol elimination after ethanol alone and after the ethanol-higher alcohol mixture. Alpha activity acid (AA) metabolism, and this has led to fears that (8-14 Hz) in the EEG was reduced by all drinks, with the ingestion of massive amounts of this vitamin a maximum fall in mean dominant frequency 2'5 hr could lead to the formation of kidney or bladder after the start of drinking. Subjects could not dis- stones. In the rats given large daily injections of AA tinguish between the three beverages, and their reports there was a sevenfold increase in the weight of calculi of the severity of effects were unrelated to the type formed round a lead hall inserted in the bladder, and of drink consumed. There was no evidence suggesting the amount of oxalic acid in the deposit was more that whiskey has unique effects not produced by eth- than doubled (Cited in F.C.T. 1967, 5, 111). In man, a single dose of 6 g AA produced a significant anol alone. increase in tile urinary content of microcrystals 60/~m or more in diameter (yon Sengbusch & Timmermann, 3339. Intestinal absorption of oxalate Urol. int. 1957, S, 218). There have also been brief Madorsky, M. L. & Finlayso.n, B. (1977). Oxalate reports of two men who passed urinary stones after taking either 2f:p,A daily for 2wk (Briggs, Lancet absorption from intestinal segments of rats. hwestve 1973, ii, 1439) or" i g daily for several months (Roth Urol. 14, 274. & Breitenfield, J. Am. reed. Ass. 1977, 237, 768), oxaOxalate is ingested in many foods, particularly late excretion in the latter case being approximately spinach, rhubarb, parsley and tea, and its excretion, halved when AA supplements were withdrawn. together with that of calcium, is important in relation Captive baboons require considerable AA suppleF.C.T. 16 5--(;