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PubMed1996

Elevated intracellular Ca2+ and myofibrillar Ca2+ sensitivity cause iodoacetate-induced muscle contractures.

Ischemic stimulation of iodoacetic acid (IAA)-treated rat extensor digitorum longus (EDL) muscles produced contractures. Similar ischemic stimulation of control EDL muscles did not result in contracture. At the onset of contracture, ATP concentration was not reduced, phosphocreatine concentration was reduced > 75%, ADP concentration was increased 9-fold, Ca2+ concentration ([Ca2+]) was increased approximately 11-fold, and inorganic phosphate concentration increased less in IAA-treated muscles than in stimulated control muscles. To test whether contracture resulted from elevated [Ca2+] and/or increased Ca2+ sensitivity of the contractile proteins, this laboratory made skinned fiber-activating solutions that simulated four different conditions: unstimulated IAA-treated and control muscles, IAA-treated muscles at contracture, and ischemically simulated control muscles. Skinned EDL fibers had lower single-fiber tensions and reduced Ca2+ sensitivities in activating solutions that mimicked the conditions in stimulated control muscles compared with activating solutions that simulated the conditions in unstimulated muscles. In contrast, the maximum tension was maintained and Ca2+ sensitivity was increased in activating solutions that simulated contracture. Tension at contracture resulted from increased intracellular [Ca2+] and increased myofibrillar Ca2+ sensitivity compared with the Ca2+ sensitivity of stimulated control fibers.

Animals↗
PubMedDate not supplied

Morphological analysis of iodoacetic acid-induced cataract in the rat.

PURPOSE: To clarify the mechanism underlying the development of cataract in the rat lens after intraperitoneal administration of iodoacetic acid (IAA). METHODS: (1) The 2% IAA dissolved in saline solution was injected at a dose of 40 mg/kg body weight into the rat peritoneal cavity. The retina and lens were intermittently extirpated and were examined by light and electron microscopy. (2) Two kinds of tracer, Evans blue (EB) and horseradish peroxidase (HRP), were injected into the tail veins and anterior chamber, and were observed with dissecting and electron microscopes. RESULTS: (1) Four weeks after administration, a part of the lens epithelium at the lateral side of the lens was degenerated, and the lens nucleus developed faint turbidity after 8 weeks. After 16 weeks, the nuclear turbidity could not be observed because mild cortical opacity was developing. The epithelial degeneration recovered from around 12 weeks, and instead of spherical nuclei, elliptical nuclei appeared. (2) The EB dye injected into the tail vein significantly stained the ciliary body, where the anterior and posterior ciliary arteries anastomosed. EB injected from the lateral side of the lens was seen to move towards the lens nucleus. Electron microscopically, the epithelial degeneration of the ciliary body was observed. The incorporated HRP substance was found in the cytoplasm of the nonpigmented cells of the ciliary epithelium at an early stage after IAA administration. CONCLUSION: IAA injected intravenously first developed epithelial degeneration at the lateral side of the lens. This change induced swelling of the lens fibers in the lens nucleus. Recovered epithelial cells had a transformed nucleus, and in turn the cortical cataract was induced by a differentiation disorder of the lens fibers. These results indicate that the breakdown of the blood-aqueous barrier in the nonpigmented epithelium of the ciliary body is a trigger to cause the cataract. The IAA-induced cataract may be useful as an animal model of human age-related cataract.

Animals↗
PubMed2003

Sodium iodoacetate-induced experimental osteoarthritis and associated pain model in rats.

Degenerative lesions were induced in the knee joint of Wistar rats by intraarticular injection of chondrocyte metabolism inhibitor mono-iodoacetate (MIA) at doses of 0, 0.3 or 3 mg/joint. Histopathological examination and the measurement of hind paw weight ratio as an index of joint pain by incapacitance tester were performed. Histological findings that are similar to those observed in human osteoarthritis (OA), such as disorganization of chondrocytes, erosion and fibrillation of cartilage surface, and subchondral bone exposure etc., were observed in a MIA-dose-dependent manner. Saflanin-O fast green staining revealed that marked diffuse reduction of proteoglycan in cartilage tissue of rats treated with MIA. The clinical scores of the joint pain were closely correlated to the grade of histological findings. We conclude that the present experimental model in combination with a novel dual channel weight averager would be very useful for the study of human OA, and could be applied for estimation of therapeutic effect of new anti-OA drugs.

Animals↗
PubMed1979

Insulin release and eflux of [32P]Phosphate from islets of rat Langerhans treated with iodoacetic acid and the anomers of D-glucose.

To clarify the insulin-releasing mechanism, we studied insulin release and the efflux of [32P]phosphate by glucose at 0.1 mM/min of gradient level or at 16.7 mM, and other metabolism in islets of rat Langerhans. When treated with 1 mM iodoacetic acid (IAA) plus the anomers of D-glucose at 2.8 mM for 6 min at 37 degrees C, islets elicited insulin at half the control rate under the step-wise stimulation by glucose and at the same rate as the control under the slow-rise stimulation by glucose. Using islets treated with IAA plus the alpha anomer at 16.7 mM, the step-wise stimulation secreted insulin at half a rate of the control and the slow-rise stimulation at the rate lower than the control, which was not significantly different from the control rate. Treatment with IAA plus the beta anomer at 16.7 mM inhibited insulin release under both types of stimulations by glucose. The step-wise stimulation caused the same rapid efflux of [32P]phosphate from IAA-treated islets as from the control islets, except for islets treated with IAA plus the beta anomer at 16.7 mM. The rate of glucose utilization in islets was inhibited by all IAA-treatments to the same extent, being merely half the control rate. Treatments with IAA plus the anomers at 16.7 mM significantly reduced the formation of [3H]-cAMP and the activity of protein phosphokinase in islets, while in the presence of the anomers at 2.8 mM IAA produced no significant effect. Neither IAA-treatments altered the uptake of 45Ca and the ATP content in islets. The uptake of [14C]IAA was significantly enhanced by the presence of the beta anomer at 16.7 mM to two times the control level. On the basis of these results, we suggested that the B cell might contain both glucoreceptors and rate-sensors of glucose controlling insulin release and the former might be less sensitive to IAA as compared with the latter.

Animals↗
PubMed1999

Effects of iodoacetate on spontaneous electrical activity, slow wave, in the circular muscle of the guinea-pig gastric antrum.

In the circular muscle of the guinea-pig gastric antrum, the contribution of glycolysis to spontaneous electrical activity, slow wave, was studied. The slow wave could be maintained without a marked change in glucose-free solution for more than 1 h even when treated with iodoacetic acid (IAA, 0.1-0.5 mM). However, reapplication of glucose following the IAA treatment produced clear inhibitory effects on the slow wave. Lactate release from the tissue was reduced to about 10% of the control by IAA (0.1 mM) in the absence of glucose and there was very slow recovery on glucose reapplication. This suggests that IAA did not block glycolysis completely and that the inhibition of slow wave was mainly due to the accumulation of some metabolites. Small electrical activity often remained during the inhibition by IAA and glucose. When the excitability of the smooth muscle was increased by Co(2+) application or Na(+) removal, slow wave-like activity could be generated under the condition in which the slow wave was strongly inhibited by IAA and glucose. These results may be explained by assuming that the accumulation of glycolytic metabolites decreases the excitability of smooth muscle cells and also reduces the driving potential generated in the interstitial cells of Cajal to a subthreshold level for the slow wave in the smooth muscle cells.

Animals↗
PubMed2003

Antitumor activities of iodoacetate and dimethylsulphoxide against solid Ehrlich carcinoma growth in mice.

Treatment of tumor-bearing mice with LD12.5 values of iodoacetate; IAA (1.84 mg/100 g b.w.) and/or dimethylsulphoxide; DMSO (350 mg/100 g b.w.) significantly increased the cumulative mean survival time and percentage of survivors and reduced the mean tumor weight, compared to tumor-bearing controls, however, a more pronounced effect is recorded in the combined treatment. Also, an increase in the life span (ILS%) and tumor growth inhibition ratio (T/C%) are reported and amounted to 145.78 and 43.80%, 195.54 and 61.30% and 220.77 and 78.40% in IAA, DMSO and combined-treated groups, respectively. Results obtained from biochemical studies reveal that a single IAA treatment of tumor-bearing mice significantly increased the levels of plasma lactate dehydrogenase (LDH) activity, while it also significantly decreased the levels of plasma glucose and liver total protein, RNA and DNA, compared to normal controls. On the other hand, a single DMSO treatment significantly elevated the activities of blood antioxidant enzymes, i.e. glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) and decreased the liver RNA and DNA levels. Combined treatment increased significantly the levels of plasma LDH and erythrocytes G6PDH activities, as well as liver glycogen, and in contrast it decreased the levels of liver total protein, RNA and DNA, compared to normal controls.

Animals↗
PubMed1976

[Tetanic fatigue and proximate post-tetanic recuperation in sartorius and flexor carpi radialis muscles of the male frog. Effects of iodoacetic acid (author's transl)].

The time-course of the isometric tension output, at 20 degrees C, during a long tetanus and after a short period of rest, was investigated in two isolated frog muscles : the sartorius and flexor carpi radialis muscles. To prevent aerobie and glycolytic recovery processes, some muscles were poisoned with 0,4 mM iodoacetic acid (IAA) and nitrogen, for 20 or 40 min. 1. For the unpoisoned sartorius muscle, tetanic tension declined quickly, but after a 0,8 sec period of rest, the muscle was able to develop high tension. Poisoning with IAA-N2 increased fatigue without suppressing the property of a proximate post-tetanic recuperation. 2. In the flexor carpi radialis muscle resistance to fatigue was very large before poisoning and diminished after poisoning. Proximate recuperation was very weak. 3. The results show that the recovery processes are not a primary factor of the development of the short-term fatigue ; they enhance the hypothesis that a failure of the electromechanical coupling can explain the rate of the tension fall in tetanized sartorius muscles.

Anaerobiosis↗
PubMed2004

In vivo micro computed tomography of subchondral bone in the rat after intra-articular administration of monosodium iodoacetate.

Osteoarthritis (OA) is a degenerative disease that is characterized by joint discomfort, loss of articular cartilage, and changes to the subchondral bone. Studies to elucidate the pathophysiology of OA have been hampered by the lack of a rapid, reproducible animal model that mimics the structural changes associated with the disease. A single intra-articular injection of mono-iodoacetate (MIA), an inhibitor of glycolysis, into the femorotibial joint of rodents promotes loss of articular cartilage similar to that noted in human OA. The purpose of the present study was to determine whether in vivo three-dimensional micro computed tomography (microCT) was of use for detecting progressive changes over time to the subchondral bone (femorotibial joint) of Wistar rats treated with a single intra-articular injection of MIA. MIA-treated right knee joints and left contralateral control knee joints were imaged in vivo at 0, 1, 7, 14, 28, and 56 days postinjection by using microCT. Analysis of 50- and 100- micro m resolution images demonstrated that changes to the subchondral bone, as determined by visual and bone mineral density analysis, are apparent by day 14 post-MIA. By day 28, there were marked changes to lateral aspect of the medial tibial plateaus of the subchondral bone in MIA-treated joints. These changes were progressive through day 56. It was concluded that intra-articular injection of MIA induces progressive changes to subchondral bone that can be assessed using in vivo microCT imaging. In light of these data, in vivo microCT imaging represents a valuable tool for investigating bone remolding and has the potential to be used for routine, high-throughput analysis and screening of investigation therapeutics.

Animals↗
PubMed2004

The influence of doxycycline on articular cartilage in experimental osteoarthrosis induced by iodoacetate.

The experiment was performed on 36 Wistar rats. On the first day of the experiment iodoacetate was administered to the left posterior knee joint of the 18 rats which composed Group I. The second group of 18 rats received additionally doxycycline (doxy) through the gastric tube in doses comparable with those of doxycycline used in humans. The experiment lasted 21 days. The animals were sacrificed after 7, 14 and 21 days in groups of 6 rats each. In sections stained with Safranin 0 semiquantitative histochemical intensity tests were performed on articular cartilage glycosaminoglycans (GAG) using a four-point scale (0-3). In the first group examined destructive lesions in the articular cartilage and weak reactivity on GAG were noted at all stages of the experiment. The intensity of GAG staining was higher in the second group after 14 and especially after 21 days, which may suggest a protective action of doxy on articular cartilage.

Animals↗
PubMed1989

Relationship between coronary flow and high energy phosphates in the isolated perfused rat heart, with special reference to the effects of anoxia, iodoacetic acid, and 2,4-dinitrophenol.

In Langendorff rat hearts, anoxia increased the coronary flow, concentration of adenosine in the coronary effluent and the tissue level of lactate, and decreased the intracellular oxygen, left ventricular pressure (LVP), heart rate and the tissue levels of adenosine triphosphate (ATP) and creatine phosphate (CrP). In the normoxic heart, an infusion of iodoacetic acid (IAA) (0.1 mg/min) increased the coronary flow, adenosine concentration in the effluent, and decreased ATP and CrP levels, without decreasing the intracellular oxygen. When glucose in the perfusate was substituted for pyruvate, IAA did not produce the pharmacological effects. In the normoxic heart, an infusion of 2,4-dinitrophenol (DNP) (50 micrograms/min) increased the coronary flow, adenosine concentration in the effluent and oxygen consumption, but decreased the intracellular oxygen, LVP and the tissue levels of ATP and CrP, without affecting the lactate level. There was no direct relationship between the coronary flow and the adenosine concentration in the effluent, but there was a close relationship between the increase in coronary flow and the total loss of myocardial ATP and CrP during anoxia, infusion of IAA, or infusion of DNP. These results indicate that the total loss of ATP and CrP from the myocardium (and hence energy state of the myocardium) may be responsible for regulation of coronary flow.

2,4-Dinitrophenol↗
PubMed1979

Studies of chemically modified histidine residues of proteins by carbon 13 nuclear magnetic resonance spectroscopy. Reaction of hen egg white lysozyme with iodoacetate.

It is shown that natural abundance 13C NMR spectroscopy can be used to determine the structures and relative amounts of chemically modified forms of a histidine residue of a peptide or protein. The unfractionated product of the reaction of N alpha-acetyl-L-histidine with bromoacetate yields four resonances of nonprotonated aromatic carbons. These resonances are assigned (on a one-to-one basis) to C gamma of the intact amino acid, the two monocarboxymethylated derivatives (at N delta1 and N epsilon2), and the dicarboxymethylated derivative. The effect of pH on the chemical shift of C gamma is characteristic for each of the four species. This property is used to study the carboxymethylation of His-15 of hen egg white lysozyme upon treatment with iodoacetate. With the use of various reaction conditions, His 15 is carboxymethylated in detectable quantities only at N epsilon2. The spectra of the various reaction mixtures indicate which conditions are best for maximizing the yield of this derivative. A comparison of the spectrum of chromatographically pure [N epsilon2-carboxymethylhistidine-15]lysozyme with that of the intact protein indicates that the chemical modification does not significantly affect the conformation of the protein (at least in the regions of all aromatic amino acid residues).

Egg White↗
PubMed1976

Different inhibitory effects of 2,4-dinitrophenol, iodoacetate, and probenecid on renal excretion of p-aminohippurate, cyclopenthiazide, and sulfamethoxypyridazine in rats.

The present study was undertaken to determine whether the renal excretion of drugs can be modified by inhibition of the carrier system for organic acids in vivo. The renal excretion of p-aminohippurate is not influenced by 2,4-dinitrophenol but is reduced by iodoacetate and probenecid. The renal excretion of cyclopenthiazide is decreased by all inhibitors. Rats excrete only a very small portion of the administered dose of sulfamethoxypyridazine. Renal sulfamethoxypyridazine excretion is 3 times higher when the tubular reabsorption is blocked by simultaneous administration of NaHCO3. However, even then only a small portion of the injected dose is excreted. Renal sulfamethoxypyridazine excretion is only reduced by probenecid. This finding can be explained by the reduction of the urine volume. It can be concluded that p-aminohippurate and cyclopenthiazide are renally excreted by tubular secretion, whereas sulfamethoxy-pyridazine is excreted by glomerular filtration.

Aminohippuric Acids↗
PubMed1976

Effects of iodoacetate and anoxia on phosphate metabolism in isolated perfused rat hearts.

When perfused with a solution equilibrated with 95% N2 and 5% CO2, the isolated rat heart was gradually depressed but continued to beat for longer than 30 min. Creatine phosphate content strikingly decreased, but lactate content was markedly elevated. When perfused with a fully oxygenated solution containing 0.5 mM of sodium iodoacetate (IAA) of the myocardial contractile force was almost unaltered and the heart rate decreased slightly within 10 min. Thereafter, the heart rate rapidly decreased, and soon cardiac arrest followed. Myocardial content of high-energy phosphates still remained at a considerably high level. The heart arrested by IAA responded to electrical stimulation, contracted and high-energy phosphates were well utilized. Addition of lactate to an oxygenated perfusate containing IAA improved myocardial performance. Citrate and palmitate did not restore the IAA-treated cardiac impairment. The results show that IAA disturbed cardiac conduction more markedly than contractility by blocking cytoplasmic glycolysis and that lactate, unlike citrate and palmitate, produced enough energy to recover cardiac activities in IAA-treated hearts.

Animals↗
PubMed1996

Spectrophotometric determination of thallium in zinc and zinc-base alloys with iodoacetic acid and hexamethylenetetramine.

Thallium(III) forms a ternary complex of yellow colour with iodoacetic acid and organic bases, especially hexamethylenetetramine. The complex is soluble in water and various organic solvents. Zinc, copper, cadmium and iron do not form complexes with these reagents, so that a spectrophotometric determination of thallium in zinc and its alloys is possible. The limit of detection is 15 microg g(-1), the molar absorption coefficient about 2000 mol(-1) l(-1) cm(-1).

Journal Article↗
PubMed2002

Investigation of bis(tributyltin)-initiated free radical cyclization reactions of 4-pentenyl iodoacetates.

Bis(tributyltin)-initiated atom transfer cyclization reactions of 4-pentenyl iodoacetates (1) at 80 degrees C led to the formations of 5-(3-iodopropyl)-substituted dihydro-2(3H)-furanones (3) in high yield. With BF3*Et2O as the catalyst, the reactions were run at room temperature to afford the corresponding gamma-iodoheptanolactones (2), which could be further transformed into 3-(tetrahydro-2-furyl)propanoic acids (6) upon treatment with aqueous NaHCO3. The reaction mechanism was postulated to be the 8-endo free radical cyclization to generate gamma-iodoheptanolactones which easily underwent intramolecular nucleophilic substitution to form bicyclic acylium species (7) as the key intermediate. Subsequent attack by iodide ion furnished gamma-lactones while attack by hydroxide ion gave the tetrahydrofuran derivatives.

Journal Article↗
PubMed2006

Aldol-type reactions of unmasked iodoacetic acid with carbonyl compounds promoted by samarium diiodide: efficient synthesis of carboxylic 3-hydroxyacids and their derivatives.

An easy, direct, general, and efficient samarium diiodide-mediated preparation of 3-hydroxyacids 1 in high yield by reaction of different aldehydes or ketones with commercially available iodoacetic acid is described. The application of different esterification procedures to the crude 3-hydroxyacids so obtained afforded the corresponding 3-hydroxyesters. Also, the cyclization of crude 3-hydroxycarboxylic acids allowed the preparation of beta-lactones. A mechanism is proposed to explain the synthesis of 3-hydroxyacids 1.

Journal Article↗