Oxalate toxicity

Evidence for renal oxalate toxicity was found from studies describing urinary enzyme excretion suggesting renal (tubular) damage in patients with stones [25]. Rat models of stone disease have been used to study such damage in greater detail and revealed brush border loss, release of cellular enzymes, and epithelial erosion [19, 26, 27]. However, all these arguments are indirect and cannot distinguish oxalate (or oxalic acid) mediated effects from calcium oxalate crystal induced effects. 

Fassett, D.W., "Oxalates," Toxicants Occurring Naturaiiy in Foods, National Academy of Sciences, 1966, pp. 259-264. 

Among adipates, oxalates, malonates, and succinates, the adipates are the least toxic. An example of this can be seen in the comparison between... 

Osmium tetroxide, reaction with alkenes, 235-236 toxicity of, 235 Oxalic add, structure of, 753 Oxaloacetic acid, structure of, 753 Oxetane, reaction with Grignard reagents, 680 Oxidation, 233, 348 alcohols, 623-626 aldehydes, 700-701 aldoses, 992-994 alkenes, 233-236 biological, 625-626 phenols, 631 sulfides, 670 thiols, 668... 

Ba oxalate is poisonous, an eye, nose, throat and skin irritant, and produces dermatitis. It is a fire and expln hazard, dangerous when heated to decompn, and emits toxic fumes (Refs 5 9)... 

Ca oxalate is corrosive and produces local irritation. It has a caustic effect on mouth, esophagus and stomach, and can cause severe damage to kidneys (Refs 6 9). It can be dangerous when heated to decompn because of toxic fumes (Ref 6)... 

Potassium Oxalata. K2C2 04. HjO, mw 184.23 colorl, odorless crysts mp, loses H20 at about 160°, when iguited is converted into carbonate without appreciable charring d 2.13g/cc, sol in 3p of w. Can be prepd by heating a mixt of K formate or carbonate with oxalic acid and a small amt of K hydroxide, with subsequent extraction of w. Highly toxic by inhalation and ingestion... 

ADH also has clinical significance in the metabolism of methanol and ethylene glycol, two drugs with toxic metabolites. Methanol is oxidized by ADH to formaldehyde, which damages the retina and can cause blindness. Ethylene glycol is metabohzed by ADH to oxalic acid, which has renal tox-... 

Vegetables also contain carboxylic acids that contribute to their flavors. One example is oxalic acid, prevalent in spinach and rhubarb. Raw rhubarb leaves are mildly poisonous, and folklore holds that the toxic substance is oxalic acid. However, raw spinach can be eaten safely despite its equally high content of this acid. 

Root exudation of extraordinary high amounts of specific carboxy lutes (e.g ci-u-ate, malate. oxalate, pbytosiderophores) in response to nutritional deficiency stress or Al toxicity in some plant species cannot simply be attributed to diffusion processes. The controlled release of these compounds, involved in mobilization of mineral nutrients and in detoxification of Al. may be mediated by more specific mechanisms. Inhibitory effects by exogenous application of various anion chan-... 

Aluminium toxicity is a major stress factor in many acidic soils. At soil pH levels below 5.0, intense solubilization of mononuclear A1 species strongly limits root growth by multiple cytotoxic effects mainly on root meristems (240,241). There is increasing evidence that A1 complexation with carboxylates released in apical root zones in response to elevated external Al concentration is a widespread mechanism for Al exclusion in many plant species (Fig. 10). Formation of stable Al complexes occurs with citrate, oxalate, tartarate, and—to a lesser extent— also with malate (86,242,243). The Al carboxylate complexes are less toxic than free ionic Al species (244) and are not taken up by plant roots (240). This explains the well-documented alleviatory effects on root growth in many plant species by carboxylate applications (citric, oxalic, and tartaric acids) to the culture media in presence of toxic Al concentrations (8,244,245) Citrate, malate and oxalate are the carboxylate anions reported so far to be released from Al-stressed plant roots (Fig. 10), and Al resistance of species and cultivars seems to be related to the amount of exuded carboxylates (246,247) but also to the ability to maintain the release of carboxylates over extended periods (248). In contrast to P deficiency-induced carboxylate exudation, which usually increases after several days or weeks of the stress treatment (72,113), exudation of carboxylates in response to Al toxicity is a fast reaction occurring within minutes to several hours... 

Calcium oxalate (723) occurs as the monohydrate (whewellite, the thermodynamically stable form under ambient conditions (724)), the dihydrate (weddellite) in plant calcium stores and in sap, or the trihydrate (725). Calcium oxalate also plays a structural role in plants. Oxalate, for example from excessive amounts of rhubarb or spinach, inhibits absorption of Ca2+ from the GIT precipitation of calcium oxalate is the reason for the toxicity of oxalates. Calcium oxalate may also occur in man, where it can appear as minute star-shaped crystals in the urine. It is the main constituent of the majority of urinary calculi in man (726,727). The relationships between dietary calcium... 

The kinetic parameters for the oxidation of a series of alcohols by ALD are shown in Table 4.1 (74). Methanol and ethylene glycol are toxic because of their oxidation products (formaldehyde and formic acid for methanol and a series of intermediates leading to oxalic acid for ethylene glycol), and the fact that their affinity for ALD is lower than that for ethanol can be used for the treatment of ingestion of these agents. Treatment of such patients with ethanol inhibits the oxidation of methanol and ethylene glycol (competitive inhibition) and shifts more of the clearance to renal clearance thus decreasing toxicity. ALD is also inhibited by 4-methylpyrazole. 

Shaffer, C.B. and West, B. (1960). The acute and subacute toxicity of technical o,o-diethyl s-2-diethyl-aminoethyl phosphorothioate hydrogen oxalate (TETRAM). Toxicol. Appl. Pharmacol. 2 1-13. 

Reproductive toxicity has been noted in animal studies. Male mice administered 8400 mg/kg for 7 days before mating had decreased fertility. Female mice given the same dose 7 days before mating and throughout 21 days of gestation showed embryotoxicity and fetotoxi-city. Female rats had disrupted estrous cycles when maintained on diets containing 2.5% and 5% oxalic acid. ... 

A second form of storage iron is haemosiderin (Weir et al., 1984). This is deposited in humans as a response to the condition of iron overload. Haemosiderin forms as insoluble granules with electron dense cores surrounded by a protein shell. It exists in two forms primary haemosiderin is the result of iron overload due to excessive adsorption of iron in the gut, whereas the secondary form is caused by the numerous blood transfusions which are used to treat thallassaemia (a form of anaemia). Electron diffraction indicated that the iron core in primary haemosiderin is a 3-line ferrihydrite with magnetic hyperfine splitting only below 4 K and, in the secondary form, consists of poorly ordered goethite. As goethite is less soluble in ammonium oxalate buffer solution (pH 3) it has a lower intrinsic toxicity (Mann et al., 1988). 

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