ABSTRACT
The effects of arsenic and ethanol interaction on blood, liver and serum biochemical indices, and arsenic concentration in soft tissues of rats were investigated to determine the influence of these substances in inducing susceptibility to arsenic poisoning. Arsenic, intraperitoneally (100 ppm, once, daily), ethanol in drinking water (10%), or the combination were administered for a period of 6 weeks. Both the chemicals had some additive effects in marginally elevating blood zinc protoporphyrin. Glutathione (GSH) concentrations of blood and liver were reduced by both arsenic and ethanol; however, there was a more pronounced depletion of hepatic GSH concentration in animals coexposed to arsenic and ethanol. Combined arsenic plus ethanol exposure led to significantly more elevated activities of serum transaminases than in animals administered arsenic or ethanol alone. Histopathological alterations in kidneys and liver occurred following arsenic exposure. Arsenic plus ethanol produced more pronounced liver lesions, whereas kidney changes were the same as with arsenic alone. The concentrations of arsenic in kidney and liver were higher in rats exposed to arsenic plus ethanol. The results suggest that animals exposed to arsenic plus ethanol are more vulnerable to arsenic toxicity.
Subject(s)
Arsenic/toxicity , Ethanol/toxicity , Alanine Transaminase/blood , Animals , Arsenic/administration & dosage , Arsenic/pharmacokinetics , Aspartate Aminotransferases/blood , Brain/metabolism , Drug Interactions , Epithelium/pathology , Ethanol/administration & dosage , Glutathione/blood , Glutathione/metabolism , Kidney/metabolism , Kidney/pathology , Kidney Tubules/pathology , Liver/metabolism , Liver/pathology , Male , Necrosis , Porphobilinogen Synthase/blood , Protoporphyrins/blood , RatsABSTRACT
Arsenic as sodium arsenite (100 ppm in drinking water) was administered to male rats for 16 weeks. Animals were then treated either with meso-2,3-dimercaptosuccinic acid (DMSA), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), dimethyl DMSA (DmDMSA), or diisopropyl DMSA (DiPDMSA) twice daily (50 mg/kg) intraperitoneally for 5 days. After 5 days of rest period, the animals were again given a second course of chelation therapy. The animals were sacrificed subsequently for the determination of whole brain biogenic amines levels, acetylcholinesterase (AChE), monoamine oxidase (MAO) and delta-aminolevulinic acid dehydratase (ALAD) activities. A number of biochemical parameters and arsenic concentrations in some tissues were also determined. The results suggest a significant increase in brain arsenic concentration accompanied by alterations in neurotransmitters levels following As(III) exposure. Although chelation treatment was effective in reducing As burden, the altered biochemical variables responded less favorably to chelation therapy. The DMSA-diesters, particularly DiPDMSA, produced a more pronounced increase in brain arsenic burden, as well as alterations in a few neurotransmitters. It can be concluded that the lipophilic character of As antidotes may lead to unfavorable results following intraperitoneal administration.
Subject(s)
Arsenic/toxicity , Brain Chemistry/drug effects , Chelating Agents/pharmacology , Neurotransmitter Agents/analysis , Alanine Transaminase/metabolism , Animals , Arsenic/metabolism , Aspartate Aminotransferases/metabolism , Biogenic Monoamines/analysis , Male , Porphobilinogen Synthase/metabolism , RatsABSTRACT
Sulphur mustard (SM) is a bifunctional alkylating agent which can react with a wide variety of molecules of biological interest. The interaction of SM with animal skin elicits a varied histopathological response in cellular components on a temporal scale. The extracellular matrix (ECM) undergoes tremendous structural changes as a result of SM exposure. Sulphur mustard induces oedema, infiltration of polymorphonuclear cells and destruction of cells. Injury appeared to be most severe on the third day after exposure, when the thickness of the skin registered the maximum change from the control. The initiation of recovery could be noticed on the 6th day, when the intercellular gap in the ECM began to reduce significantly, indicating reformation of damaged skin. Simultaneous reformation was also noticed in the epidermis and other cellular components. However, recovery was far from complete and continued beyond the 6th day.
Subject(s)
Mustard Gas/toxicity , Skin/drug effects , Skin/pathology , Animals , Male , Rabbits , Skin/ultrastructureABSTRACT
The therapeutic efficacy of two thiol chelators, meso 2,3-dimercaptosuccinic acid (DMSA) or 2,3-dimercaptopropane sulfonate (DMPS) in treating chronic arsenic intoxication was investigated in male rats. Both the chelators were effective in promoting urinary arsenic excretion and restoring arsenic induced inhibition of blood delta-aminolevulinic acid dehydratase activity and hepatic glutathione level. Elevation of urinary delta-aminolevulinic acid excretion and arsenic concentration in blood, liver and kidneys were reduced significantly by both the chelators. Histopathological lesions induced by arsenic were also effectively reduced by the above chelators. DMSA being more effective than DMPS. The results suggest DMSA and DMPS to be effective antidotes for treating chronic arsenic toxicity in experimental animals.
