PMID- 15450858 OWN - NLM STAT- MEDLINE DCOM- 20050315 LR - 20151119 IS - 1532-0456 (Print) IS - 1532-0456 (Linking) VI - 138 IP - 2 DP - 2004 Jun TI - Effects of superoxide dismutase and polyclonal tumor necrosis factor-alpha antibodies on chloroacetate-induced cellular death and superoxide anion production by J774.A1 macrophages. PG - 113-20 AB - Dichloroacetate (DCA) and trichloroacetate (TCA) are by-products that are formed during the process of water chlorination and have been previously shown to induce superoxide anion (SA) production and cellular death when added to J774.A1 macrophage cultures. In this study, the effects of superoxide dismutase (SOD) and polyclonal tumor necrosis factor-alpha (TNF-alpha) antibodies on DCA- and TCA-induced SA production and cellular death have been tested on the J774.A1 macrophage cultures. TCA and DCA were added to different cultures either alone, each at a concentration of 16 mM, or in combination with SOD (2-12 units/ml), or with TNF-alpha antibodies (10 and 25 units/ml). Cells were incubated for 48 h, after which cellular death/viability, lactate dehydrognase (LDH) leakage by the cells, and SA production by the cells were determined. While TCA and DCA caused significant cellular toxicity, indicated by reduction in cellular viability and increases in LDH leakage and SA production, SOD addition resulted in significant reduction of the effects induced by the compounds. On the other hand, addition of TNF-alpha antibodies to the DCA- and TCA-treated cultures resulted in significant reduction of DCA- but not TCA-induced cellular death and SA production by the cells. Although these results suggest a significant role for SA in DCA- and TCA-induced cellular death, they may also suggest two different mechanisms for the chloroacetate-induced SA production by the cells. FAU - Hassoun, Ezdihar A AU - Hassoun EA AD - Department of Pharmacology, College of Pharmacy, The University of Toledo, 2801 W. Bancroft Street, OH 43606, USA. ehassou@utnet.utoledo.edu FAU - Kini, Vidisha AU - Kini V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Comp Biochem Physiol C Toxicol Pharmacol JT - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP JID - 100959500 RN - 0 (Acetates) RN - 0 (Antibodies) RN - 0 (Tumor Necrosis Factor-alpha) RN - 11062-77-4 (Superoxides) RN - 5GD84Y125G (chloroacetic acid) RN - EC 1.15.1.1 (Superoxide Dismutase) SB - IM MH - Acetates/*toxicity MH - Animals MH - Antibodies/pharmacology MH - Cell Death/drug effects/physiology MH - Cell Line MH - Cell Survival/drug effects/physiology MH - Macrophages/*drug effects/metabolism MH - Mice MH - Superoxide Dismutase/*pharmacology MH - Superoxides/*metabolism MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 2004/09/29 05:00 MHDA- 2005/03/16 09:00 CRDT- 2004/09/29 05:00 PHST- 2004/01/28 00:00 [received] PHST- 2004/05/07 00:00 [revised] PHST- 2004/05/08 00:00 [accepted] PHST- 2004/09/29 05:00 [pubmed] PHST- 2005/03/16 09:00 [medline] PHST- 2004/09/29 05:00 [entrez] AID - S1532045604001000 [pii] AID - 10.1016/j.cca.2004.05.008 [doi] PST - ppublish SO - Comp Biochem Physiol C Toxicol Pharmacol. 2004 Jun;138(2):113-20. doi: 10.1016/j.cca.2004.05.008.