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Antidotal effects of 2,3–dimercaptoprop ane– 1–sulfonic acid (DMPS) and meso–2,3– dimercaptosuccinic acid (DMSA) on the organotoxicity of dibutyltin dichioride (DBTC) in rats

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Rostock, Germany; University of Rostock, Institute of Experimental and Clinical Pharmacology and Toxicology, Schillingallee 70, 18057 Rostock, Germany

H Weber

Institute of Clinical Chemistry and Pathobiochemistry, University of Rostock, Germany

G Krdning

G Hennighausen

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Rostock, Germany

1. 1 Dialkyltin compounds have been widely used in industry and agriculture, mainly as biocides, catalysts and plast stabilizer. In dependence on the length of the alkyl chains these organotins exert toxic effects on the immune system, the bile duct, liver and pancreas. It has been supposed that similar to organoarsenic the toxicity of the dialkyltin compounds is related to reactions with biological dithiol groups. Therefore, in the present study, the antidotal effects of 2,3-dimer-capto-propane-l-sulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the organotoxic effects of dibutyltin dichloride (DBTC, single adminis-tration of 27,umol kg-' b.w. i.v.) in rats were studied using different doses (100 and 500 limol kg-1 b.w.) and routes of administration (i.p. and p.o.) of both chelators. Several parameters of organotoxicity (thy-mus weight and cellularity, bile duct diameter, histological lesions of pancreas and liver, activities of amylase, lipase and alkaline phosphatase, bilirubin and hyaluronic acid in serum) were measured from 6 h to 8 weeks.
   
2. 2 DMPS and DMSA diminished the DBTC induced bile duct, pancreas and liver lesions stronger than the thymus atrophy. Moreover, the development of a fibrosis of the pancreas and a cirrhosis of liver several weeks after single administration of DBTC to rats was inhibited by DMPS and DMSA. The antidotal effects on serum parameter were observed after both adminis-tration routes of the chelators. DMPS was more effective than DMSA in most measured parameters. The decrease in the biliary excretion of organotin by DMPS and DMSA seems to be the reason for the pronounced protective effects of DMPS and DMSA on bile duct, pancreas and liver.
   
3. 3 For the treatment of poisonings with dibutyltin compounds, the administration of DMPS or DMSA can be recommended.
   

Key Words: dibutyltin dichloride • 2,3–dimercaptopropane–1–sulfonic acid • meso–2,3–dimercaptosuccinic acid • biliary excretion • pancreatitis • liver lesions

Human & Experimental Toxicology, Vol. 19, No. 2, 132-137 (2000)
DOI: 10.1191/096032700678815701


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