Late administration of COX-2 inhibitors minimize hepatic necrosis in chloroform induced liver injury.

Our previous studies have described the protective effects of hepatoprotective agents against liver injury elicited by chloroform even when given 24 h after the toxicant, at a time when the liver injury is taking place and rapidly developing. However, the mechanisms involved in this protection remain unknown. The cytoprotective mechanism of these hepatoprotectants such as DMSO, may be due to a dramatic shift in the production of prostaglandins that are responsible for controlling the degree of inflammatory response that can affect blood flow in the liver. In this study, NS-398, a specific COX-2 inhibitor, and indomethacin, a COX-1 and COX-2 inhibitor, were administered 24 h after chloroform dosing to determine their effect on liver injury in Sprague-Dawley rats. The extent of necrosis was evaluated by H&E staining, while injury to hepatocytes was evaluated by measuring plasma levels of alanine transaminase (ALT). Both COX inhibitors, indomethacin and NS-398, prevented an increase in (ALT) at 48 h after initial toxicant insult and attenuated further liver necrosis. No changes in cellular proliferative activity occurred in all the treatment groups, which indicates that protection from the Cyclooxygenase (COX) inhibitors did not have an effect on regeneration of cells at 32 and 48 h. These results indicate COX inhibitors provide a significant protective effect on liver cells against CHCl(3) injury and may provide further insight into therapeutic interventions against hepatotoxicants.

Fate of effluent organic matter during soil aquifer treatment: biodegradability, chlorine reactivity and genotoxicity.

Hydrophobic acid (HPO-A) and transphilic acid (TPI-A) fractions of dissolved organic matter (DOM) were isolated from a domestic secondary wastewater effluent that was polished via soil aquifer treatment (SAT). Fractions were isolated using XAD resin adsorption chromatography from samples obtained along the vadose zone flowpath at a full-scale basin recharge facility in Tucson, Arizona. Changes in isolate character during SAT were established via biodegradability (batch test), specific ultraviolet light absorbance (SUVA), trihalomethane formation potential (THMFP), and Ames mutagenicity assays. The dissolved organic carbon (DOC) concentration decreased by >90% during SAT. A significant fraction (up to 20%) of isolated post-SAT HPO-A was biodegradable. The (apparent) refractory nature of DOM that survives SAT may be a consequence of low DOC concentration in groundwater as well as the nature of the compounds themselves. Specific THMFP (microg THM per mg DOC) of HPO-A and TPI-A varied little as a consequence of SAT, averaging 52 and 49 microg THM per mg DOC, respectively. The nonbiodegradable fractions of HPO-A and TPI-A exhibited higher reactivities: 89 and 95 microg THM per mg DOC, respectively. Genotoxicity of HPO-A (on a per mass basis) increased after SAT, suggesting that responsible compounds are removed less efficiently than bulk organics during vadose zone transport.