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      Antimony Toxicity

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          Abstract

          Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically.

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          Mechanisms of action of arsenic trioxide.

          J Singer, Samuel Waxman, S Lee … (2002)
          Arsenic trioxide has shown substantial efficacy in treating both newly diagnosed and relapsed patients with acute promyelocytic leukemia (APL). As a single agent, it induces complete remissions, causing few adverse effects and only minimal myelosuppression. These successes have prompted investigations to elucidate the mechanisms of action underlying these clinical responses. Substantial data show that arsenic trioxide produces remissions in patients with APL at least in part through a mechanism that results in the degradation of the aberrant PML-retinoic acid receptor alpha fusion protein. Studies have also investigated concerns about the toxicity and potential carcinogenicity of long-term exposure to environmental arsenic. Arsenic apparently affects numerous intracellular signal transduction pathways and causes many alterations in cellular function. These actions of arsenic may result in the induction of apoptosis, the inhibition of growth and angiogenesis, and the promotion of differentiation. Such effects have been observed in cultured cell lines and animal models, as well as clinical studies. Because arsenic affects so many cellular and physiological pathways, a wide variety of malignancies, including both hematologic cancer and solid tumors derived from several tissue types, may be susceptible to therapy with arsenic trioxide. These multiple actions of arsenic trioxide also highlight the need for additional mechanistic studies to determine which actions mediate the diverse biological effects of this agent. This information will be critical to realizing the potential for synergy between arsenic trioxide and other chemotherapeutic agents, thus providing enhanced benefit in cancer therapy.
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            Recommendations for treating leishmaniasis with sodium stibogluconate (Pentostam) and review of pertinent clinical studies.

            L Herwaldt, Gordon J. Berman (1992)
            Pentavalent antimonial compounds have been the mainstay of the treatment of visceral, cutaneous, and mucosal leishmaniasis for approximately half a century. Pentostam (sodium stibogluconate) is the pentavalent antimonial compound available in the United States (through the Centers for Disease Control). As dosage regimens for treating leishmaniasis have evolved, the daily dose of antimony and the duration of therapy have been progressively increased to combat unresponsiveness to therapy. In the 1980s, the use of 20 mg/kg/day (instead of 10 mg/kg/day) of antimony was recommended, but only to a maximum daily dose of 850 mg. The authors have concluded on the basis of recent efficacy and toxicity data that this 850-mg restriction should be removed; the evidence to date, which is summarized here, suggests that a regimen of 20 mg/kg/day of pentavalent antimony, without an upper limit on the daily dose, is more efficacious and is not substantially more toxic than regimens with lower daily doses. We recommend treating all forms of leishmaniasis with a full 20 mg/kg/day of pentavalent antimony. We treat cutaneous leishmaniasis for 20 days and visceral and mucosal leishmaniasis for 28 days. Our judgment of cure is based on clinical criteria.
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              Placebo-controlled clinical trial of sodium stibogluconate (Pentostam) versus ketoconazole for treating cutaneous leishmaniasis in Guatemala.

              Judith Berman, Mercedes Arana, T Navin … (1992)
              To determine the relative efficacy and toxicity of stibogluconate and ketoconazole for the treatment of cutaneous leishmaniasis, a comparative trial was conducted in which 120 Guatemalan men with parasitologically proven cutaneous leishmaniasis were randomly divided into three treatment groups: sodium stibogluconate (20 mg of antimony per kilogram per day intravenously for 20 days), ketoconazole (600 mg per day orally for 28 days), and placebo. Treatment outcome was influenced by species. Among patients infected with Leishmania braziliensis, 24 (96%) of 25 in the stibogluconate group but only 7 (30%) of 23 in the ketoconazole group responded. Among Leishmania mexicana-infected patients, only 4 (57%) of 7 in the stibogluconate group but 8 (89%) of 9 in the ketoconazole group responded. These differences emphasize the importance of speciation in the treatment of leishmaniasis.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Environ Res Public Health
                Journal ID (publisher-id): 101238455
                Title: International Journal of Environmental Research and Public Health
                Publisher: Molecular Diversity Preservation International (MDPI)
                ISSN (Print): 1661-7827
                ISSN (Electronic): 1660-4601
                Publication date (Print): December 2010
                Publication date (Electronic): 20 December 2010
                Volume: 7
                Issue: 12
                Pages: 4267-4277
                Affiliations
                Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India; E-Mail: tapadar@ 123456gmail.com
                Author notes
                * Author to whom correspondence should be addressed; E-Mail: drshyamsundar@ 123456hotmail.com ; Tel.:+91-542-236-7795; Fax: +91-542-2367568.
                Article
                Publisher ID: ijerph-07-04267
                DOI: 10.3390/ijerph7124267
                PMC ID: 3037053
                PubMed ID: 21318007
                SO-VID: c0f38468-51c1-4f8e-9db6-c102f5ece995
                Copyright © © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
                License:

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 15 November 2010
                Date accepted : 15 December 2010
                Categories
                Subject: Review

                ScienceOpen disciplines: Public health
                Keywords: occupational hazard,toxicity,antimony,leishmaniasis
                Data availability:
                ScienceOpen disciplines: Public health
                Keywords: occupational hazard, toxicity, antimony, leishmaniasis

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