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  Discussion on Glyoxal, treating for the liver, and other urgent questions
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New Member:
rebella

Posted on Thursday, Jul 24, 2008 - 5:06 pm:

I can't believe I'm asking these questions and I have my own answers after researching for the last 7 days but Dr. O, I could use some timely advice.
1)My mare was diagnosed with cholangial hepatitis based on "slightly" elevated liver enzymes. I know your thinking on that and I disagree with the diagnosis as well. The GGT was 32 and the AST was 314. It has since gone down even more but my question concerns the use of SMZ-TMP to treat a liver infection. Doesn't that seem counter productive? Was wondering your thoughts on that?
2)The "diagnosing" vet then referred me to another vet for some homeopathic treatments. Believe me, both of these vets are considered highly qualified in this area. I am in the midst of this bee hive and it is a current on going condition but my second question regards the highly poisonous and homeopathic chemical called glyoxal. Why in the world would anyone ever inject this sub cu. and into a horses main arteries? Why would this be done without the owners permission or knowledge? And are you aware of any antidotes one week after injection? Or is too late for potential long term chronic and even fatal conditions? My horse suffered what looked like a mild paralysis for about 48 hours after the injections. She acted like everything was in slow motion. On the third day she developed swelling in all 4 legs for approximately 24 hours. The "homeopathic" vet did not ever mention what she had been injected with, after numerous consulatation over her symptoms, until I asked for a list of all materials on the 5th day after injection. I can hardly believe this and am shocked but my immediate concern is for the welfare of my mare. I do not trust any vets from this area at this point. Can you please point me in the right direction. I had tons of blood work done yesterday but it won't all be back in for 2 or 3 more days, including specific liver and thyroid panels. I am monitoring her 24/7 myself and I have taken her off everything except her hay and vitamin/supplements.She is a bit grouchy, all vitals are normal and is eating and drinking normal. She is much more quiet than normal.
Moderator:
DrO

Posted on Friday, Jul 25, 2008 - 8:51 am:

Welcome Rebela,
Taking your questions one at a time:
1) Concerning TMP-SMZ use in liver infection, counterproductive how? If an infection is sensitive to the antibiotic and reaches significant concentration in the affected tissue why not use it?
2) I am unfamiliar with glyoxal as a treatment or toxin much less an antidote. Searching the net and PubMed there is nothing on its use as a treatment that I can find. Have you discussed with the veterinarian the reason for the use of this compound? What was the dosage rate and route of each injection?

The most informative thing on toxicity I could find was this review from Inter-Organization Programme for the Sound Management of Chemicals (IOMC). Note that NOAEL stands for: "No observable adverse effect level":

8.1 Single exposure
The acute toxicity of glyoxal in experimental animals is low to moderate, depending on the actual concentration of glyoxal in the tested product. However, from the documentation in the study reports, it is not always clear if the values given for the LC50 or LD50 refer to the tested product with its specified concentration or if the values were converted to a concentration of 100% glyoxal. A detailed compilation of acute toxicity data is given in the source document (BUA, 1997).

An LC50 value of 2440 mg/m3 (2410 mg/m3 for females, 2470 mg/m3 for males) was calculated from single 4-h inhalation exposures of rats to aerosols of 40% glyoxal (Hoechst AG, 1984b). All 10 rats exposed by inhalation to an atmosphere containing dust of 80% glyoxal in the highest technically feasible concentration of 1300 mg/m3 survived (Hoechst AG, 1984c). All rats survived 7- and 8-h exposures to concentrated atmospheres (concentration not further specified) of 30% (Mellon Institute, 1958, 1965) or 40% glyoxal (Hoechst AG, 1984d,e). After inhalative uptake, observations reported included local irritations of the eyes and respiratory organs as well as hyperaemia and foamy secretion in the lungs. No macroscopic organ changes were reported in those rats surviving the 14-day post-observation period (Hoechst AG, 1984d,e).

After oral administration to rats, LD50 values ranging from 2960 mg/kg body weight (lowest value in females) to 8979 mg/kg body weight (highest value in males) were reported in several studies using products containing 40% glyoxal, demonstrating a higher sensitivity of female rats. In mice (sex not given), the LD50 of 40% glyoxal was 4064 mg/kg body weight. For a preparation containing 80% glyoxal, oral LD50 values of 2000 mg/kg body weight in rats and 900 mg/kg body weight in guinea-pigs were found. Macroscopic observations reported after oral uptake include irritations of the gastrointestinal tract and congestions in the gastrointestinal tract, lung, kidney, and adrenal glands (BUA, 1997).

After dermal administration of 40% glyoxal, the LD50 values were >2000 mg/kg body weight for the rat, 12 700 mg/kg body weight for the rabbit, and >5000 mg/ kg body weight for the guinea-pig (for details, see BUA, 1997).

In the 1940s to 1960s, histopathological findings in studies with acute application of glyoxal pointed to a connection between effects induced by glyoxal and those induced in the course of diabetes; this has been confirmed by recent intensive studies on the mechanism of action of endogenous glyoxal and its involvement in the development of diabetic complications (see section 8.8).

Pancreas and kidney were identified as the prominent target organs of the toxic action of glyoxal; severe degenerative changes in these organs were attributed to an inhibition of glyoxalase activity in these tissues. Changes in the pancreas were dominated by the observation of necrotic areas containing B-cells of the Langerhans islets in rabbits (105 mg glyoxal/kg body weight intracardial or two administrations of 320 mg/kg body weight subcutaneous) and in cats (227 mg/kg body weight, application not specified). A simultaneous increase of blood glucose levels was demonstrated in rabbits and cats, comparable to alloxan-induced diabetes (Doerr et al., 1948). The pancreas is a prominent target organ of alloxan toxicity, too, which is mediated by free radicals (Younes, 1997). Rats responded to intravenous injection of 100-200 mg glyoxal/kg body weight with a dose-dependent, reversible, and reproducible reduction of the blood glucose level, which was attributed to a glyoxal-stimulated secretion of insulin secondary to oedematous changes of the pancreas. At higher dosage (175 mg/kg body weight intravenous), more severe changes, such as irreversible necroses and degranulation of B-cells, were observed in connection with visible changes in other organs. However, the B-cells of the pancreas showed the highest sensitivity to the toxic action of glyoxal (Helge, 1959). The nephrotoxic action of glyoxal is characterized by vacuole degeneration in the kidney (460 mg glyoxal per cat subcutaneous) (Doerr, 1957a,b). Acute effects noted in the pancreas in several studies all seemed to arise when glyoxal was administered parenterally, compared with other routes. This may be due to toxicokinetic reasons.

A further study in rabbits described histopathological changes in liver, kidney, and pancreas 40 days after a single dermal application of a 40% glyoxal solution (leading to severe necrotic dermatitis at application site; dose not specified). Granular and vacuole degeneration in liver, kidney, and pancreas and atrophy and fibrous change of Langerhans islets were assessed to show a close resemblance to changes in these tissues in the course of diabetes. In glucose tolerance tests performed 5 and 10 days after dermal application of glyoxal, a distinct increase of blood glucose levels was observed in comparison with a constant level in control rabbits (Ito, 1963).

8.2 Short-term exposure In an inhalation study conducted according to OECD guideline 412, groups of five male and five female Wistar rats inhaled aerosols containing glyoxal (40% in water) at 0, 0.4, 2.0, or 10 mg/m3 (analytical concentrations 0, 0.6, 2.3, and 8.9 mg/m3; mass median aerodynamic diameter 0.8-1.2 µm) for a period of 29 days (nose only, 6 h/day, 5 days/week). Exposure was tolerated by all dose groups without any systemic effects (examination of body weight, haematological and biochemical parameters, urine analysis, macroscopic and histological examination). The only local effect found in the larynx was a minimal squamous metaplasia of the epiglottal epithelium accompanied by a minimal submucosal infiltration of lymphocytes in the mid- and high-dose groups. Consequently, for local effects, a NOEL of 0.6 mg/m3 (nominal concentration 0.4 mg/m3) resulted for subacute inhalation exposure of rats to glyoxal (Hoechst AG, 1995).

In a 28-day oral toxicity study conducted according to OECD guideline 407, six male and six female Sprague-Dawley rats per dose group were exposed to glyoxal (40% in water) at dosages of 0, 100, 300, or 1000 mg/kg body weight per day via the drinking-water. A dose-dependent retardation of body weight gain in the mid-dose group (slight effect) and the high-dose group (significant effect) was accompanied by reduced food intake. A dose-dependent reduction of water intake was observed in male rats at the lowest dose and in female rats at the mid- and high doses (glyoxal concentrations were adjusted to water intake). Changes in mid- and high-dose groups, such as increased erythrocyte number and reduced urine volume, were attributed to reduced water intake; changes of various organ weights in the high-dose group were attributed to reduced body weight. No changes were found at macroscopic and histological examination. The NOAEL for this study is 100 mg glyoxal/kg body weight per day (Société Française Hoechst, 1987). (More details were not available to the authors of this CICAD. It is not known whether these concentrations are adjusted to 100% glyoxal. If not, the NOAEL would be about 40 mg/kg body weight adjusted to 100% glyoxal.)

DrO
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