L-cystein protects the pigment epithelium from acute sodium iodate toxicity

Heike, M; Marmor, Michael F.

doi:10.1007/bf00142589

Cited by 9 publications

(7 citation statements)

References 5 publications

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“…The retinal pigment epithelium is the primary target of iodate toxicity and this toxicity is associated with the oxidizing properties of iodate, because the damage threshold is lowered by other oxidizers (43) and raised by antioxidants, e.g., glutathione, given shortly before, or combined with, iodate. When given 30 minutes after an intravenous iodate bolus the retinal pigment epithelium, and subsequently the retina, can no longer be protected by glutathione (42). Many other phenomena have been described during investigation of the pathogenetic sequence outlined here.…”

Section: Oculotoxicitymentioning

confidence: 85%

The Toxicology of Iodate: A Review of the Literature

Bürgi¹,

Schaffner²,

Seiler³

2001

Thyroid

140

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Because it is more stable than iodide, most health authorities preferentially recommend iodate as an additive to salt for correcting iodine deficiency. Even though this results in a low exposure of at most 1,700 microg/d, doubts have recently been raised whether the safety of iodate has been adequately documented. In humans and rats, oral bioavailability of iodine from iodate is virtually equivalent to that from iodide. When given intravenously to rats, or when added to whole blood or tissue homogenates in vitro or to foodstuff, iodate is quantitatively reduced to iodide by nonenzymatic reactions, and thus becomes available to the body as iodide. Therefore, except perhaps for the gastrointestinal mucosa, exposure of tissues to iodate might be minimal. At much higher doses given intravenously (i.e., above 10 mg/kg), iodate is highly toxic to the retina. Ocular toxicity in humans has occurred only after exposure to doses of 600 to 1,200 mg per individual. Oral exposures of several animal species to high doses, exceeding the human intake from fortified salt by orders of magnitude, pointed to corrosive effects in the gastrointestinal tract, hemolysis, nephrotoxicity, and hepatic injury. The studies do not meet current standards of toxicity testing, mostly because they lacked toxicokinetic data and did not separate iodate-specific effects from the effects of an overdose of any form of iodine. With regard to tissue injury, however, the data indicate a negligible risk of the small oral long-term doses achieved with iodate-fortified salt. Genotoxicity and carcinogenicity data for iodate are scarce or nonexisting. The proven genotoxic and carcinogenic effects of bromate raise the possibility of analogous activities of iodate. However, iodate has a lower oxidative potential than bromate, and it did not induce the formation of oxidized bases in DNA under conditions in which bromate did, and it may therefore present a lower genotoxic and carcinogenic hazard. This assumption needs experimental confirmation by proper genotoxicity and carcinogenicity data. These in turn will have to be related to toxicokinetic studies, which take into account the potential reduction of iodate to iodide in food, in the intestinal lumen or mucosa, or eventually during the liver passage.

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Section: Oculotoxicitymentioning

confidence: 85%

The Toxicology of Iodate: A Review of the Literature

Bürgi¹,

Schaffner²,

Seiler³

2001

Thyroid

140

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“…11-13 NaIO 3 possesses selective toxicity for the RPE cells, although large doses cause photoreceptor cell damage. 11 NaIO 3 -induced retinal toxicity is seen in a variety of animal species, such as rabbits, 11,[13][14][15][16][17] sheep, 18 rats, 19 as well as in mice. 20 Although NaIO 3 has been used extensively as a retinotoxin, there are few reports concerning the precise sequential morphological observation which define the mode of retinal cell death.…”

Section: Introductionmentioning

confidence: 99%

Morphologic characteristics of retinal degeneration induced by sodium iodate in mice

Kiuchi

Yoshizawa

Shikata

et al. 2002

Current Eye Research

128

104

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“…45 The combined effects of bisretinoid photoxidative stress and NaIO 3 likely compromise cellular oxidant defense. For instance, both sources of stress can reduce intracellular glutathione levels 22,46 and the damage mediated by both NaIO 3 16 and bisretinoid photooxidative damage 47 can be ameliorated by chelation of labile iron. The pronounced ONL thinning that we observed is also consistent with the view that RPE cell dysfunctioning leading to photoreceptor cell degeneration can precede overt RPE cell loss.…”

Section: Discussionmentioning

confidence: 99%

“…21 Moreover, cotreatment with cysteine or glutathione reduces the damage to RPE caused by NaIO 3 . 22 When oxidative stress is induced with NaIO 3 , an age-related increase in superoxide anion and malondialdehyde is observed. 13 It is also reported that murine and human RPE cells cultured in the presence of NaIO 3 are induced to generate reactive oxygen species.…”

mentioning

confidence: 99%

Multimodal Fundus Imaging of Sodium Iodate-Treated Mice Informs RPE Susceptibility and Origins of Increased Fundus Autofluorescence

Kim

Sparrow

2017

Invest. Ophthalmol. Vis. Sci.

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PurposeBy multimodal imaging, and the use of mouse and in vitro models, we have addressed changes in fundus autofluorescence (488 and 790 nm) and observed interactions between the photooxidative stress imposed by RPE bisretinoid lipofuscin and the oxidative impact of systemic sodium iodate (NaIO3).MethodsAbca4−/−, wild-type, and Rpe65rd12 mice were given systemic injections of NaIO3 (30 mg/kg). Analysis included noninvasive imaging of fundus autofluorescence (short-wavelength [SW-AF]; near-infrared excitation [NIR-AF]), quantitative fundus AF (qAF; 488 nm); light microscopy, RPE flat-mounts and measurements of outer nuclear layer (ONL) thickness. NaIO3 also was studied by using in vitro assays.ResultsIn SW-AF and NIR-AF images, fundus mottling was visible 3 and 7 days after NaIO3 injection with changes being more pronounced in Abca4−/− mice that are characterized by an abundance of RPE bisretinoid lipofuscin. In Abca4−/− mice, qAF was elevated 3 and 7 days after NaIO3 administration. In light micrographs and RPE flat-mounts stained to reveal tight junctions (ZO-1) and nuclei, the RPE monolayer was disorganized, and clumping and loss of RPE was visible. ONL thinning was most pronounced in Abca4−/− mice. Treatment of ARPE-19 cells with NaIO3 together with the photooxidation of the bisretinoid A2E by exposure to 430-nm light produced an additive effect whereby loss of cell viability was greater than with either perturbation alone.ConclusionsElevations in SW-AF intensity can occur due to photoreceptor cell dysfunction as induced secondarily by NaIO3. Photooxidative stress associated with RPE cell bisretinoid lipofuscin may confer increased susceptibility to the oxidant NaIO3.

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L-cystein protects the pigment epithelium from acute sodium iodate toxicity

Cited by 9 publications

References 5 publications

The Toxicology of Iodate: A Review of the Literature

The Toxicology of Iodate: A Review of the Literature

Morphologic characteristics of retinal degeneration induced by sodium iodate in mice

Multimodal Fundus Imaging of Sodium Iodate-Treated Mice Informs RPE Susceptibility and Origins of Increased Fundus Autofluorescence

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