ABSTRACT
The therapeutic efficacy of chelating agents CaNa3DTPA (calcium trisodium diethylene triamine penta acetic acid) and Tiron (sodium-4,5-dihydroxy-1,3-benzene disulphonate) with and without antioxidant, alpha-Tocopherol was evaluated in the treatment of beryllium-induced toxicity in female albino rats. The animals were exposed to beryllium (as beryllium nitrate) at a dose of 1 mg/kg (ip) once a day for 28 consecutive days followed by chelation therapy by CaNa3DTPA (0.1 mM/kg, ip) and Tiron (471 mg/kg, ip) with and without alpha-Tocopherol (25 mg/kg, orally) for 5 consecutive days after toxicant administration. Tissue biochemistry revealed severe alterations in liver and kidney. A significant fall in total protein and glycogen contents, alkaline phosphatase, adenosine tri-phosphatase and succinic dehydrogenase level was noticed. On the contrary, an elevation in acid phosphatase was recorded. The significant rise in hepatic lipid peroxidation and decreased level of hepatic reduced glutathione showed toxicity due to beryllium. CaNa3DTPA with alpha-Tocopherol showed moderate therapeutic efficacy while Tiron in combination with alpha-Tocopherol exerted statistically more beneficial effects to reverse biochemical alterations in different variables altered due to beryllium intoxication.
Subject(s)
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt/pharmacology , Adenosine Triphosphatases/metabolism , Alkaline Phosphatase/metabolism , Animals , Antioxidants/pharmacology , Beryllium/pharmacology , Chelating Agents/pharmacology , Drug Therapy, Combination , Female , Glutathione/metabolism , Glycogen/metabolism , Kidney/drug effects , Lipid Peroxidation , Liver/drug effects , Magnesium/metabolism , Nitrates/pharmacology , Pentetic Acid/pharmacology , Rats , Rats, Sprague-Dawley , Succinate Dehydrogenase/metabolism , Time Factors , alpha-Tocopherol/metabolismABSTRACT
In vitro effect of aluminium (Al) on Fe(2+)-induced lipid peroxidation (LPX) in various subcellular fractions from the cerebral hemispheres (CH) of 7- and 30-day old chicks was studied. Stimulation of Fe(2+)-induced LPX by Al was observed to be the highest in microsomal fraction. The magnitude of elevation of Fe(2+)-induced LPX in various subcellular fractions of brain showed age related variation. Of the six chemicals tested for their influence on Al-induced lipid peroxidation, both doses of 1,2-dihydroxybenzene-3,5-disulphonic acid disodium salt (Tiron), ethylene diamine tetra acetic acid disodium salt (EDTA), and ascorbic acid prevented the Al-induced LPX in crude homogenates of the CH, whereas only at a higher dose inhibition by 1,4-diazabicyclo (2.2.2.) octan (DABCO) was observed. On the contrary, mannitol and dimethyl sulfoxide did not inhibit the induction of LPX by Al in crude homogenate. The effect of test chemicals on Al-induced LPX in both the ages of chick tissue was almost similar. The results suggest that Al further augments Fe(2+)-induced LPX in various compartments of the cell due to generation of free radicals. The results also showed that Tiron, EDTA and antioxidants, such as ascorbic acid and DABCO can prevent LPX induced by Al.