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
The present study was undertaken to investigate the role of calcium ions (Ca2+) in the induction and secretion of the dengue type 2 virus induced cytotoxic factor and the cytotoxin. This was done by using calcium channel blocking drugs such as verapamil, nifedipine or diltiazem hydrochloride. The production of cytotoxic factor was significantly reduced by treatment of dengue type 2 virus infected mice with verapamil. Similarly, a dosedependent inhibition of the secretion of cytotoxic factor was observed, when spleen cells of the virus-primed mice were treated in vitro with the 3 calcium channel blockers. The production of cytotoxin by macrophages was abrogated by pretreatment with calcium channel blockers but had little effect on its secretion as shown by treatment of macrophages with verapamil at 1 h after the induction to later periods up to 18 h. The findings thus show that in the induction of both the cytokines Ca2+ plays a critical role; on the other hand it is required for the secretion of the cytotoxic factor but not for that of the cytotoxin.