Effects Of Iodoacetic Acid Research Articles

Effect of iodoacetic acid on the reproductive system of male mice.

Iodoacetic acid (IAA) is one of the most common water disinfection byproducts (DBPs). Humans and animals are widely and continuously exposed to it. Many species of water DBPs are harmful to the reproductive system of organisms. Nevertheless, the potential effects of IAA exposure on testosterone and spermatogenesis in vivo remain ambiguous. Spermatogenous cells are the site of spermatogenesis, Leydig cells are the site of testosterone synthesis, and Sertoli cells build the blood–testis barrier (BTB), providing a stable environment for the aforementioned important physiological functions in testicular tissue. Therefore, we observed the effects of IAA on spermatogenic cells, Leydig cells, and Sertoli cells in the testis. In this study, we found that oral administration of IAA (35 mg/kg body weight per day for 28 days) in male mice increased serum LH levels and reduced sperm motility, affecting average path velocity and straight line velocity of sperm. In addition, IAA promoted the expression of γH2AX, a marker for DNA double-strand breaks. Moreover, IAA downregulated the protein expression of the scavenger receptor class B type 1 (SRB1), and decreased lipid droplet transport into Leydig cells, which reduced the storage of testosterone synthesis raw materials and might cause a drop in testosterone production. Furthermore, IAA did not affect the function of BTB. Thus, our results indicated that IAA exposure affected spermatogenesis and testosterone synthesis by inducing DNA damage and reducing lipid droplet transport.

The effects of iodoacetic acid on the mouse retina.

To characterize the effects of intravitreal injections of iodoacetic acid (IAA) in comparison to its systemic application as a measure to induce unilateral photoreceptor degeneration. Seven-week-old C57BL/6 J mice received either intravitreal injections of IAA or systemic treatment (intraperitoneal vs intravenous) and were observed in the following 5 weeks using ERG, OCT, and histology. Systemic treatment with IAA induced high toxic effects and a high mortality in contrast to the intravitreal injection. Intraperitoneal application had no effect on the retina. Intravenous application of 2 × 30 mg/kg BW IAA (time between injections 3.5 h) resulted in an extinction of the ERG and a thinning of the retina, in particular of the outer nuclear layer (ONL) indicating photoreceptor degeneration. Animals receiving intravitreal injections developed cataracts already at low concentrations (up to 100% at 0.25 mg/kg BW). Higher intravitreal IAA doses led to extinguished ERGs. In histology, a thinning of the entire retina was observed that was most prominent in the inner part of the retina. In contrast to intraperitoneal administration, intravenous application of IAA led to a selective photoreceptor degeneration. After intravitreal injection, dense cataracts were already observed at concentrations lower than those needed to induce changes in the ERG. ERG results must be interpreted carefully. A thinning of all retinal layers rather than a specific outer retinal degeneration was observed upon intravitreal injection. IAA is not a useful model to induce outer retinal degeneration in mice.

Dual regulation of heat-shock transcription factor (HSF) activation and DNA-binding activity by H2O2: role of thioredoxin.

The heat-shock (HS) response is a ubiquitous cellular response to stress, involving the transcriptional activation of HS genes. Reactive oxygen species (ROS) have been shown to regulate the activity of a number of transcription factors. We investigated the redox regulation of the stress response and report here that in the human pre-monocytic line U937 cells, H2O2 induced a concentration-dependent transactivation and DNA-binding activity of heat-shock factor-1 (HSF-1). DNA-binding activity was, however, lower with H2O2 than with HS. We thus hypothesized a dual regulation of HSF by oxidants. We found that oxidizing agents, such as H2O2 and diamide, as well as alkylating agents, such as iodoacetic acid, abolished, in vitro, the HSF-DNA-binding activity induced by HS in vivo. The effects of H2O2 in vitro were reversed by the sulphydryl reducing agent dithiothreitol and the endogenous reductor thioredoxin (TRX), while the effects of iodoacetic acid were irreversible. In addition, TRX also restored the DNA-binding activity of HSF oxidized in vivo, while it was found to be itself induced in vivo by both HS and H2O2. Thus, H2O2 exerts dual effects on the activation and the DNA-binding activity of HSF: on the one hand, H2O2 favours the nuclear translocation of HSF, while on the other, it alters HSF-DNA-binding activity, most likely by oxidizing critical cysteine residues within the DNA-binding domain. HSF thus belongs to the group of ROS-modulated transcription factors. We propose that the time required for TRX induction, which may restore the DNA-binding activity of oxidized HSF, provides an explanation for the delay in heat-shock protein synthesis upon exposure of cells to ROS.

Iodoacetate-induced skeletal muscle contracture: changes in ADP, calcium, phosphate, and pH.

The effects of iodoacetic acid (IAA) and ischemic contraction were studied in rat extensor digitorum longus muscles. Ischemic stimulation of IAA-treated muscles produced contracture. We measured total muscle water content, distribution of water between intracellular and extracellular spaces, creatine concentration ([Cr]), creatine phosphate concentration ([PCr]), [ATP], [Pi], intracellular pH, and intracellular Ca2+ concentration ([Ca2+]i) at the onset of contracture. [ADP] was calculated from the equilibrium of the creatine kinase reaction using the measured values of [ATP], [PCr], [Cr], and pH. At the onset of contracture there was a 75% reduction of [PCr], a 12-fold increase in [ADP], and an 11-fold increase in [Ca2+]i compared with unstimulated IAA-treated muscles. [ATP] was not depleted at contracture compared with unstimulated IAA-treated muscles, and [Pi] increased less in muscles at contracture compared with stimulated control muscles. The persistent tension in contractures probably resulted from increased [Ca2+]i combined with increased myofibrillar Ca2+ sensitivity due to elevated [ADP] and relatively reduced intracellular acidification and [Pi].

Iodoacetate-induced contracture in rat skeletal muscle: possible role of ADP

The effects of iodoacetic acid (IAA) and ischemic contraction were studied in rat extensor digitorum longus muscles. Ischemic contraction of IAA-treated muscles produced contracture. The onset of contracture was not associated with a change in sarcolemmal electrical properties or reduction in intracellular [ATP]; however, [creatine phosphate] was reduced by 75% and free [ADP] was increased by 665%. Continued stimulation of IAA-treated fibers resulted in depolarization, loss of membrane excitability, further depletion of creatine phosphate, and reduction in [ATP]. The effects seen in IAA-treated muscle did not appear to result from a direct action of IAA on the surface membrane, contractile proteins, or excitation-contraction coupling. The contractures in IAA-treated muscle may have resulted from increased Ca sensitivity of the contractile proteins, increased myoplasmic [Ca], or both. Both effects may have resulted from increased [ADP]. In addition, the reduced acidification during ischemic contraction of IAA-treated fibers compared with control fibers may have further increased the Ca sensitivity of IAA-treated fibers compared with controls.

The effect of iodoacetic acid on the electroretinogram and oscillatory potentials in rabbits

It has been shown that a single injection of iodoacetic acid selectively (but temporarily) abolishes the b-wave of the electroretinogram. We examined whether such use of this chemical further substantiate our claim that the b-wave of the electroretinogram is a composite potential resulting from the summation (or integration) of faster retinal potentials, usually referred to as the oscillatory potentials. Full-field electroretinograms were recorded from adult New Zealand rabbits before and after a single, bolus injection of 15 mg/kg of buffered iodoacetic acid. Both the 1-1000 Hz electroretinogram and the 100-1000 Hz oscillatory potentials were recorded simultaneously. The oscillatory potentials considered in this study were those normally seen on the rising phase of the b-wave. Following the intravenous injection of iodoacetic acid, there was a progressive decrease in the amplitude and peak time of the b-wave. This observation also was reflected in the oscillatory potential recordings, in which the long-latency oscillatory potentials (3 and 4) progressively disappeared while oscillatory potential 2 remained. We believe that these findings further support our contention that the oscillatory potentials are major components of the b-wave.

Effect of iodoacetic acid upon cochlear potentials

Lotz et al. [Inner Ear Biology, INSERM, 233 (1977)] reported that perilymphatic application of 5 × 10−3 M iodoacetic acid (IAA) does not influence the first‐order cochlear microphonics (CM1). However, in ischemia the rate of decline of CM11 was significantly increased by IAA. The authors concluded that glycolysis plays no role in the maintenance of the CM1, but that it is responsible for supporting the CM11. In carefully controlled experiments we were unable to reproduce these findings. Both the endolymphatic potential (EP) and the CM declined drastically due to perfusion with 5 × 10−3 M IAA (within 10 min the EP dropped to −58 ± 4.5 mV (SD), and the CM declined to about 6% of the control). The CM was abolished after 45 min of perfusion with 5 × 10−3 M IAA, while it persisted for periods exceeding 120 rain in total anoxia. We cannot account for the discrepancy between our findings on CM1 and those of Lotz et al. Nevertheless, our experiments confirm the hypothesis that the CM11 is supported by anaerobic glycolysis. In addition, we observed an anoxia sensitive negative component of the EP in severe intoxication with IAA, a phenomenon hitherto considered peculiar to intoxication with “loop” diuretics. [Supported by NIH grant NS06575.]

Effect of iodoacetic acid on ERG and retinal ultrastructure

Effect of iodoacetic acid on ERG and retinal ultrastructure

Experimental degeneration of the rabbit retina induced by iodoacetic acid: A study of the ultrastructure, the rhodopsin cycle and the uptake of 14C-labeled iodoacetic acid

The effect of iodoacetic acid on the ultrastructure and the rhodopsin cycle of the retina of light- and dark-adapted rabbits and the uptake of intravenously injected [2-14C]iodoacetic acid were studied. Electron microscopy of both light- and dark-adapted animals showed a severe and irreversible involvement of the visual cells, starting about 3 hr after intravenous administration of iodoacetic acid (20 mg/kg bodyweight). The complete destruction of the photoreceptors was preceded by some reactive changes, such as the appearance of membrane-rich, “dark” mitochondria in the inner segments and the swelling of the outer limbs. The rhodopsin content of the degenerating retina remained at an almost normal level for a long time after the appearance of the first ultrastructural changes. The rhodopsin content started to decrease only when the swollen outer segments began to break down. After intravenous injection of radioactive iodoacetic acid, the retina, without the retinal pigment epithelium, exhibited the highest radioactivity levels compared with other ocular tissues and fluids and brain tissue. The findings are discussed with relationship to the morphological course of the retinal damage caused by iodoacetic acid and its mechanism of action on the vertebrate retina. The great affinity of iodoacetic acid for the retinal tissue may explain the selective damaging of the visual cells by this poison.

A study on the fine structure and the rhodopsin cycle of the rabbit retina in experimental degeneration induced by diaminodiphenoxypentane

The effect of diaminodiphenoxypentane (968 A: May & Baker, Dagenham, England) on the ultrastructure and the rhodopsin cycle of the retina of light- and dark-adapted rabbits was studied. Electron microscopy studies of both light- and dark-adapted animals showed an almost simultaneous involvement of the retinal pigment epithelium and the outer segments of the visual cells, starting about 30 hr after the intravenous administration of diaminodiphenoxypentane (40 mg/kg body weight). In later stages of treatment migration of histiocytes from the choroid into the damaged outermost retina, followed by diffuse gliosis, was also observed. In light-adapted rabbits rhodopsin resynthesis was markedly impaired at the time of early damage to the retinal pigment epithelium, while in dark-adapted animals a somewhat later decrease of the rhodopsin content of the retina was observed. The above results indicated that the degree of action of diaminodiphenoxypentane was intermediate, between the sodium iodate effect (primarily involving the retinal pigment epithelium) and the effect of iodoacetic acid (involving the photoreceptors). The impairment of rhodopsin resynthesis in the light-adapted animals was clearly dependent upon the extent of damage to the pigment epithelium, which participates in the rhodopsin cycle, and to a lesser extent upon the break-down of the rhodopsin-containing outer segments of the visual cells. On the other hand, in the dark-adapted animals (where synthesis by the pigment epithelium was not active) the decrease of rhodopsin content of the retina was possibly related only to the degeneration of the outer segments of the photoreceptors.

Effects of Iodoacetic Acid on the Incorporation of Phosphorus-32 into the Deoxyribonucleic Acid of some Radiosensitive Organs in Rats exposed to X-Rays

IT is now known that iodoacetic acid is able to sensitize mice1,2 and rats3 to ionizing radiations as well as cultured mammalian cells4 and bacteria (Bridges, B. A., personal communication).

Investigation of the mechanism of the action of dimethyllaurylbenzyl-ammonium chloride (ajatin) on rough and smooth forms of yeast cells

The effect of Ajatin on oxygen consumption in the presence of some intermediates and products of glycolysis was investigated together with the effect of iodoacetic acid, in order to elucidate further the higher sensitivity of the rough forms of yeast to Ajatin and to explain the synergic action of Ajatin and iodoacetic acid in the presence of glucose. It was found that the oxidation of ethanol and acetate by the rough form of distiller’s yeast is much more sensitive to the action of Ajatin than the oxidation of glucose, whereas in the smooth form the difference in sensitivity between these two processes is less. The consumption of oxygen in the presence of ethanol or acetate as substrate is markedly inhibited by iodoacetic acid in the smooth form but is not affected by this inhibitor in the rough form.

Research on the mode of action of halogen containing thiol alkylating agents on insects. Effect of iodoacetic acid on choline acetylase

The authors have studied the action of iodoacetic acid on choline acetylase of the nervous tissue of Musca domestica and Periplaneta americana. No inhibition of enzymic activity even at high doses (8 LD 50s) of iodoacetic acid has been found.

Effect of iodoacetic acid on the total excretion of sodium and potassium in rats exposed to x-rays.

Gli autori hanno studiato l'effetto dell'acido iodoacetico sulla escrezione totale di sodio e di potassio nel ratto irradiato. Essi hanno trovato che in seguito al trattamento combinato con acido iodoacetico e radiazioni l'escrezione di sodio risulta notevolmente aumentata rispetto a quella riscontrata negli animali soltanto irradiati.

Effects of iodoacetic acid on ocular inflammatory responses.

Introduction In a previous study 1 evidence was produced that systemic administration of iodoacetic acid (IAA) and ionizing radiation, when administered to the eye only, elicit very similar ocular lesions. The clinical and histological changes produced by these two different agents in the lens and retina of rabbits correlate surprisingly well. However, there were some significant differences observed with regard to the latent periods of the exudative changes in the aqueous humor and vitreous (Table 1). The exudation appeared somewhat earlier after irradiation than after IAA. The most puzzling feature, however, was presented by the fact that the leading cell type in the exudate of irradiated eyes consisted of polymorphonucleocytes, whereas the exudate in the eyes of IAA-treated animals was dominated by red blood cells. Such a difference in the exudative manifestations was difficult to understand and certainly was in contradiction to the commonly favored view that both IAA and

Effect of iodoacetic acid on oxygen consumption and survival of newborn mice.

When newborn mice are given injections of iodoacetic acid (IAA), it is found that doses of 10 mg/kg have little effect upon oxygen consumption. Doses of 60 mg/kg block all oxygen uptake within 1 hour. The animals given 10 mg/kg will survive, in air, for nearly 24 hours, while those given 60 mg/kg all die within 1 hour. If exposed to nitrogen after the injection, animals given 10 mg/kg survive as well as uninjected mice, while those given 50–60 mg/kg show the rapid death (within 3 min.) that has been reported by others. Calculations, based on probable oxygen content of the blood and other tissues of the newborn mouse, and on the minimum rate of oxygen utilization which will permit survival, show that the oxygen stores within the animal are sufficient to maintain the minimal rate of metabolism for extended periods in the absence of an external source of oxygen. Failure of the mice to survive exposure to nitrogen after IAA injection appears to depend on blocking the use of these oxygen stores as well as blocking glycolysis.

Effects of Iodoacetic Acid on the Coenzyme A Content of the Muscle of the American Cockroach1

Effects of Iodoacetic Acid on the Coenzyme A Content of the Muscle of the American Cockroach1

Tissue metabolism and peripheral circulation. I. Effect of iodoacetic acid on the metabolism of muscles "in vivo".

Tissue metabolism and peripheral circulation. I. Effect of iodoacetic acid on the metabolism of muscles "in vivo".

Tissue metabolism and peripheral circulation. II. Effect of iodoacetic acid on peripheral circulation.

Tissue metabolism and peripheral circulation. II. Effect of iodoacetic acid on peripheral circulation.

THE RELATION BETWEEN THE FOUR-CARBON ACIDS AND THE GROWTH OF OAT SEEDLINGS

Plant growth hormones are noted for the multiplicity of their effects. This is particularly true of the auxins, which are known to influence elongation of roots and shoots, determination of root number, production of callus tissue, tropistic responses, correlative growth of plant organs and protoplasmic streaming. The most striking feature about the variety of these auxin effects is the fact that any one concentration of the hormone will often stimulate one process, inhibit another, and have no effect on a third. If the concentration is varied these relations may be completely altered. Such effects, together with the fact that the auxins have an effect on protoplasmic streaming, have suggested that these hormones must play a decisive r6ole in some fundamental and common intracellular process. For some time attempts had been made to demonstrate a link between auxin and cell respiration. Experiments showed, however, that auxin had no demonstrable effect on the respiratory rate of plant cells (Bonner, 1936; Van Hulssen, 1936) and the conclusion was drawn that the hormone had no respiratory effect (DuBuy, 1940). More recently, however, Commoner and Thimann (1941) have shown that indole-3-acetic acid is directly related to the activity of a specific respiratory process, the 4-carbon dicarboxylic acid system. They showed that the salts of these acids (malic, fumaric, and succinic) will enhance the effect of auxin on growth and that the inhibitory effect of iodoacetic acid on growth is due to a specific inhibition of this system. It was shown that the 4-carbon acid system normally accounted for only 5-10 per cent of the total respiration, but that all the growth is dependent upon its activity. Thus it was demonstrated that auxin can stimulate the respiratory activity of this system (and in this way increase the rate of oxygen consumption) and that the effect of the 4-carbon acids on respiration is enhanced by the presence of auxin. This work dealt with a single effect of auxin, the elongation of ex314