Efficacy of N-Acetylcysteine, Glutathione, and Ascorbic Acid in Acute Toxicity of Paraoxon to Wistar Rats: Survival Study.

There are a great number of reports with assertions that oxidative stress is produced by organophosphorus compound (OPC) poisoning and is a cofactor of mortality and morbidity in OPC toxicity. In addition, antioxidants have been suggested as adjuncts to standard therapy. However, there is no substantial evidence for the benefit of the use of antioxidants in survival after acute intoxication of OPCs. The present study was conducted to assess the effectiveness of three non-enzymatic antioxidants (NEAOs), N-acetylcysteine (NAC), glutathione (GSH), and ascorbic acid (AA), in acute intoxication of adult male Wister rats with paraoxon. The efficacy of the antioxidants was estimated as both a pretreatment and a concurrent application along with the standard oxime, pralidoxime (2-PAM). Relative risk of death after 48 hours of application was estimated by Cox regression analysis. The results revealed no benefit of either tested NEAO to the improvement in survival of experimental rats. The application of these antioxidants was found to be deleterious when administered along with pralidoxime compared to the treatment with pralidoxime alone. It has been concluded that the tested non-enzymatic antioxidants are not useful in acute toxicity for improving survival rates. However, the individual toxic dynamics of diversified OPCs should not be overlooked and further studies with different OPCs are suggested.

Protective effects of the antihistamine promethazine aginst acute paraxon-methyl and dicrotophos toxicity in adult rats.

Organophosphorus compound poisoning (OPC) is a global issue. The problem is aggravated with the threats of terrorist use, unintentional use and irresponsible practice as happened recently in turmoil countries. The purpose of the current study was to investigate the old-generation antihistamine promethazine (PROM), a drug with multi pharmacological actions, as an antidote to extremely and highly toxic (WHO's class IA and IB) OPC poisoning in experimental animal models conducted on adult male wistar rats. Experimental groups were treated intraperitoneal (i.p.) with LD70 of methyl paraoxon (MPOX), class IA and dicrotophos (DCP), class IB alone and a combination of simultaneously i.p. injection of PROM. Mortality was recorded at 30 minutes, 1, 2, 3, 4, 24, 48 hours post injections. RBC-AChE was measured in survivals. MPOX was chosen for further studies with atropine (ATR) and pralidoxime (PAM). In addition to Kaplan-Meir survival analysis, serum lactate dehydrogenase (LDH) and creatinine kinase (CK) from serum were measured in all experimental groups with MPOX. The results revealed significant protection by PROM in both MPOX and DCP intoxicated rats, though the inhibition of RBC-AChE was high. The observed results show that groups treated with a combination of MPOX and PROM or MPOX, PROM, and PAM were protected higher than those treated with MPOX and ATR or MPOX, ATR, and PAM though statistically not significantly different (P ≤ 0.05). No effect was observed on the activity of LDH and CK. The study concludes that PROM may be effectively used in OPC poisoning. However, risk/benefits trials and further studies with different doses and other OPC groups are warranted.

MTAP: the motif tool assessment platform.

BACKGROUND: In recent years, substantial effort has been applied to de novo regulatory motif discovery. At this time, more than 150 software tools exist to detect regulatory binding sites given a set of genomic sequences. As the number of software packages increases, it becomes more important to identify the tools with the best performance characteristics for specific problem domains. Identifying the correct tool is difficult because of the great variability in motif detection software. Consequently, many labs spend considerable effort testing methods to find one that works well in their problem of interest. RESULTS: In this work, we propose a method (MTAP) that substantially reduces the effort required to assess de novo regulatory motif discovery software. MTAP differs from previous attempts at regulatory motif assessment in that it automates motif discovery tool pipelines (something that traditionally required many manual steps), automatically constructs orthologous upstream sequences, and provides automated benchmarks for many popular tools. As a proof of concept, we have run benchmarks over human, mouse, fly, yeast, E. coli and B. subtilis. CONCLUSION: MTAP presents a new approach to the challenging problem of assessing regulatory motif discovery methods. The most current version of MTAP can be downloaded from http://biobase.ist.unomaha.edu/