Influence of chelating agents on the toxicity and distribution of beryllium in rats

Shukla, Sangeeta; Sharma, Pragya; Johri, Sonia; Mathur, R.

doi:10.1002/(sici)1099-1263(1998090)18:5<331::aid-jat517>3.0.co;2-0

Cited by 12 publications

(10 citation statements)

References 16 publications

(18 reference statements)

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“…Mathur et al (1993) have investigated the efficacy of three polyaminocarboxylic acids -ethylenediaminetetraacetic acid (CaNa 2 EDTA), diethylenetriamine pentaacetic acid (CaNa 3 DTPA) and N-(2-hydroxyethyl)-ethylenetriaminetriacetic acid (HEDTA) -against beryllium toxicity. Preliminary studies confirm the efficacy of Tiron, significantly over the other chelators Shukla et al 1998). …”

Section: Discussionmentioning

confidence: 99%

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Protective effect of Tiron (4,5-dihydroxybenzene-1,3-disulfonic acid disodium salt) against beryllium-induced maternal and fetal toxicity in rats

Sharma

Shah

Shukla

2002

Archives of Toxicology

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The efficacy of Tiron (4,5-dihydroxybenzene 1,3-disulfonic acid disodium salt) was examined in the treatment of beryllium-induced maternal and developmental toxicity in rats. Single administration of beryllium nitrate at a dose of 50 mg/kg (i.m.) on day 13 of gestation caused reductions in fetal and placental weights, the number of implantation sites and number of corpora lutea, as well as causing post-implantation loss, stunted growth, increase in the number of resorptions, and also a disturbed sex ratio. Maternal toxicity was demonstrated by reduction in body weight gain. Administration of beryllium also showed significant alteration in the hematological and biochemical indices of the mother as well as the fetus. Marked decreases were recorded in hemoglobin percentage, blood sugar levels, serum protein contents and serum alkaline phosphatase activity. By contrast, significant elevation was found in the activity of transaminases (aspartate aminotransferase and alanine aminotransferase). Tissue protein contents, glycogen contents, activities of alkaline phosphatase, adenosine triphosphatase and succinic dehydrogenase of kidney, lungs and uterus, and maternal and fetal liver all showed significantly decreased values after beryllium exposure, and remarkable elevation was observed in acid phosphatase, glucose-6-phosphatase and hepatic lipid peroxidation. These parameters were restored considerably with administration of 471 mg/kg i.m. Tiron from days 14 to 18 of gestation. Atomic absorption spectrophotometry also revealed a high concentration of beryllium in different organs of pregnant rats. Interestingly, a small amount of metal ion was also detected in the fetus and reduced accumulation of beryllium was noticed after Tiron treatment.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, , and Shukla et al (1998) have reported the efficacy of Tiron (4,5-dihydroxybenzene-1,3-disulfonic acid disodium salt) against beryllium intoxication in preliminary studies, so the present study was planned to investigate the efficacy of Tiron on pregnant female rats and developing fetuses.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of Tiron (4,5-dihydroxybenzene-1,3-disulfonic acid disodium salt) against beryllium-induced maternal and fetal toxicity in rats

Sharma

Shah

Shukla

2002

Archives of Toxicology

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“…Chelators are common forms of therapy used to eliminate beryllium from the body and reduce its toxic effects. Relevant chelators include 4,-dihydroxy-1,3-benzene disulphonic acid disodium salt (Tiron) and D-penicillamine (DPA), which proved to be effective when tested in animals [35][36][37]. Also, the chelator meso-2,3-dimercaptosuccinic acid (DMSA) was used in a case study to successfully save a child suffering from heavy metal poisoning [38].…”

Section: Berylliummentioning

confidence: 99%

Heavy Metals and Cancer

Carver¹,

Gallicchio²

2018

Cancer Causing Substances

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There has been increased concern surrounding exposure to heavy metals due to the evolving understanding of their role in the development of cancer. This review highlights research related to the impact that heavy metals aluminum, arsenic, beryllium, cadmium, lead, mercury, nickel and radium have on human health. Research was collected through PubMed, and it was compiled to assess the current knowledge of exposure sources, types of cancers induced and therapeutic measures for these metals. Furthermore, it was designed to assist in guiding future research efforts with respect to heavy metals and cancer.

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“…In this paper, we looked into the therapeutic potential of three organic ligands, nitrilotripropionic acid (NTP), nitrilotriacetic acid (NTA) and 4,5-dihydroxy-1,3-benzenedisulfonic acid (tiron) using an adapted version of the human BeLPT performed on mouse splenocytes, hereafter named the splenocyte proliferation test (SPT). These chelators were selected from an in-depth literature search on appropriate beryllium complexing agents (Price and Joshi, 1984;Scarrow et al, 1985;Clevette et al, 1989;Mathur et al, 1993;Chinea et al, 1995;Shukla et al, 1998;Cecconi et al, 2002;Sharma et al, 2002;Kontoghiorghes, 1995). Based on coordination chemistry and basicity of the donor groups, we selected NTP given that the beryllium cation in the [Be(NTP)] − complex lies at the center of a slightly distorted tetrahedron towards C 3ν symmetry with a longer Be-N bond and three equal Be-O bonds.…”

Section: Introductionmentioning

confidence: 99%

“…NTA belongs to the same family of amino carboxylic acids as NTP and was selected to evaluate the potential preference of beryllium towards ligands that form five-membered ring chelates (acetic groups) or six-membered ring chelates (proprionic groups) (Chinea et al, 1995). From immunotoxicological studies, tiron was also chosen because it has been shown to reduce berylliuminduced hematological alterations and histopathological lesions in the liver (Shukla et al, 1998). Tiron was also shown to mobilize beryllium and restore the altered biochemical parameters in different rat tissues and organs Nirala et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Use of proliferation tests to evaluate the effects of complexing agents on beryllium toxicity

Stephan

Sauvé

Fournier

et al. 2008

J of Applied Toxicology

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Occupational exposure to beryllium may cause chronic beryllium disease (CBD), a granulomatous interstitial pneumonitis caused by a cell-mediated immune response with delayed hypersensitivity initiated by an electrostatic interaction with the MHC class II human leukocyte antigen (HLA). Increased research efforts focus on the development of a CBD treatment by chelation therapy. This work presents an in vitro evaluation of the beneficial effects of beryllium chelation with different organic substrates. We have used a standard beryllium lymphocyte proliferation test (BeLPT) adapted for mouse splenocytes. Three complexing agents, 4,5-dihydroxy-1,3-benzenedisulfonic acid (tiron), nitrilotripropionic acid (NTP) and nitrilotriacetic acid (NTA), were tested using different protocols of the splenocyte proliferation test (SPT). We studied their corrective effect (beryllium pre-exposed splenocytes), their protective effect (ligand pre-exposed splenocytes) and their combined effects at fixed Be:L ratio of 1:2, at fixed Be concentration and at fixed L concentration. We also studied the effect of tiron in preventing splenocyte sensitization to beryllium. All three complexing agents showed a corrective effect and proved efficient in the combined effects, except NTA in the fixed Be:L ratio. Only NTP and tiron showed a significant protection at lower beryllium concentrations, while NTA was not significant. Splenocytes pre-exposed to chelated beryllium did not show sensitization while splenocytes pre-exposed to beryllium were sensitized. We observed a strong correlation between the efficiency of the complexing agent and its affinity towards beryllium. Both tiron and NTP showed a similar affinity towards the beryllium ion that is 10(7) higher than that of NTA.

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Influence of chelating agents on the toxicity and distribution of beryllium in rats

Cited by 12 publications

References 16 publications

Protective effect of Tiron (4,5-dihydroxybenzene-1,3-disulfonic acid disodium salt) against beryllium-induced maternal and fetal toxicity in rats

Protective effect of Tiron (4,5-dihydroxybenzene-1,3-disulfonic acid disodium salt) against beryllium-induced maternal and fetal toxicity in rats

Heavy Metals and Cancer

Use of proliferation tests to evaluate the effects of complexing agents on beryllium toxicity

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