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Reversal of cadmium induced oxidative stress by chelating agent, antioxidant or their combination in rat. 2003

S K Tandon, and S Singh, and S Prasad, and K Khandekar, and V K Dwivedi, and M Chatterjee, and N Mathur
Chemical Toxicology, Industrial Toxicology Research Center, Post Box 80, Lucknow 226001, India. sktandon19@yahoo.com

The influence of an antioxidant agent such as N-acetyl cysteine (NAC) or mannitol on the cadmium chelating ability of monoisoamyl 2,3-dimercaptosuccinate (MiADMS) was investigated in cadmium pre-exposed rats. This ester of 2,3-dimercaptosuccinic acid (DMSA), an accepted drug for lead poisoning, being lipophilic in nature was expected to be an efficient cadmium chelator. The treatment of cadmium intoxicated animals with MiADMS reversed cadmium induced increase in blood catalase, superoxide dismutase (SOD) and malondialdehyde (MDA), liver MDA and brain SOD and MDA levels but not the decrease in blood, liver brain reduced glutathione (GSH) and increase in oxidized glutathione (GSSG) levels, consistent with the lowering of tissue cadmium burden. The administration of NAC or mannitol reversed the cadmium induced alterations in blood and liver GSH, GSSG, blood catalase, SOD, MDA, liver SOD, MDA and brain MDA levels without lowering blood and tissue cadmium contents. However, treatments with the combination of MiADMS and NAC or MiADMS and mannitol reversed these alterations as well as reduced blood and tissue cadmium concentrations. The combined treatment with MiADMS and mannitol was better than that with MiADMS and NAC, and was significantly more effective in normalizing blood, liver GSH, GSSG, brain GSSG, and their GSH/GSSG ratios than that by either of them alone. The combined treatments also improved liver and brain endogenous zinc levels, which were decreased due to cadmium toxicity. The results suggest that the administration of an antioxidant during chelation of cadmium may provide beneficial effects by reducing oxidative stress without its cadmium removing ability.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008315 Malondialdehyde The dialdehyde of malonic acid. Malonaldehyde,Propanedial,Malonylaldehyde,Malonyldialdehyde,Sodium Malondialdehyde,Malondialdehyde, Sodium
D008353 Mannitol A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. (L)-Mannitol,Osmitrol,Osmofundin
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002105 Cadmium Poisoning Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. Itai-Itai,Poisoning, Cadmium,Cadmium Poisonings,Itai Itai,Poisonings, Cadmium
D002374 Catalase An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA. Catalase A,Catalase T,Manganese Catalase,Mn Catalase
D002614 Chelating Agents Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS. Chelating Agent,Chelator,Complexons,Metal Antagonists,Chelators,Metal Chelating Agents,Agent, Chelating,Agents, Chelating,Agents, Metal Chelating,Antagonists, Metal,Chelating Agents, Metal
D004113 Succimer A mercaptodicarboxylic acid used as an antidote to heavy metal poisoning because it forms strong chelates with them. DMSA,Dimercaptosuccinic Acid,2,3-Dimercaptosuccinic Acid,Butanedioic Acid, 2,3-Dimercapto-, (R*,S*)-Isomer,Chemet,Ro-1-7977,Succicaptal,Succimer Antimony Sodium Salt, (R*,S*)-Isomer,Succimer, (R*,R*)-(+,-)-Isomer,Succimer, Dipotassium Salt,Succimer, Disodium Salt,Succimer, Monosodium Salt,Succimer, Rhenium Salt,Succimer, Tin Salt,Tin Dimercaptosuccinate,meso-Dimercaptosuccinic Acid,2,3 Dimercaptosuccinic Acid,Acid, 2,3-Dimercaptosuccinic,Acid, Dimercaptosuccinic,Acid, meso-Dimercaptosuccinic,Dimercaptosuccinate, Tin,Dipotassium Salt Succimer,Disodium Salt Succimer,Monosodium Salt Succimer,Rhenium Salt Succimer,Ro 1 7977,Ro17977,Tin Salt Succimer,meso Dimercaptosuccinic Acid
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug

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