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

Nurulain SM, Ojha S, Tekes K, Shafiullah M, Kalasz H, Adem A - Oxid Med Cell Longev (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Cumulative relative risk of death overtime after coapplication of compounds. Cumulative relative risk (RR) of death overtime with simultaneous intraperitoneal (i.p.) injection of POX, PAM and NAC, and GSH and AA. The legends on the side are depicting the treatment groups. RR was estimated by Cox [23] analysis, adjusted for POX dose (high/low) for each of the time points examined (30 min and 1, 2, 3, 4, 24, and 48 h). Best protection was conferred by simultaneous PAM treatment only and poor protection was estimated for all non-enzymatic treatment alone. Efficacy of PAM was estimated to decrement when co-administered with antioxidants.
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fig1: Cumulative relative risk of death overtime after coapplication of compounds. Cumulative relative risk (RR) of death overtime with simultaneous intraperitoneal (i.p.) injection of POX, PAM and NAC, and GSH and AA. The legends on the side are depicting the treatment groups. RR was estimated by Cox [23] analysis, adjusted for POX dose (high/low) for each of the time points examined (30 min and 1, 2, 3, 4, 24, and 48 h). Best protection was conferred by simultaneous PAM treatment only and poor protection was estimated for all non-enzymatic treatment alone. Efficacy of PAM was estimated to decrement when co-administered with antioxidants.

Mentions: The relative risk of death at the seven time points (30 min, 1, 2, 3, 4, 24, and 48 h), estimated by Cox [23] analysis in simultaneous oxime and antioxidant-treated animals is depicted in Figure 1 and Table 3. Table 1 shows the percentage of mortalities at different time points of observation. RR was compared with untreated animals (Group 1, RR = 1) and adjusted for paraoxon dose (high/low). Statistical comparison was performed on the cumulative relative risk, that is, the area under the RR-time curve. Simultaneous pralidoxime treatment significantly reduced the paraoxon-induced mortality, RR; 0.33 ± 0.03 (P < 0.05) as compared to the no-treatment group (G1; paraoxon only). Simultaneous treatment of  NEAO yielded no significant protection. RR was 1.04 ± 0.04, 1.08 ± 0.03, and 0.85 ± 0.28 for NAC, GSH, and AA treatment, respectively. When antioxidants were administered together with PAM, AA treatment group produced statistically significantly higher mortality (RR 1.30 ± 0.12; P < 0.014) than no-treatment group, POX. NAC and GSH applied concurrently with PAM reduced the mortality in comparison with no-treatment group. Pattern of RR for pretreatment with antioxidants was almost the same as mentioned earlier (Figure 2, Tables 2 and 4); that is, only PAM pretreatment provided significant protection (RR 0.34 ± 0.03; P < 0.05). Antioxidant pretreatment without PAM yielded poor protection. RR estimated for NAC was 1.31 ± 0.24; GSH 0.93 ± 0.30; and AA 1.09 ± 0.33. The PAM efficacy was found to be decreased when animals were pretreated with antioxidants. RR values were 0.63 ± 0.15 for NAC, 0.93 ± 0.30 and 1.29 ± 0.0.18 for AA pretreatment, respectively, in comparison with RR 0.47 ± 0.17 for POX + PAM.


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

Nurulain SM, Ojha S, Tekes K, Shafiullah M, Kalasz H, Adem A - Oxid Med Cell Longev (2015)

Cumulative relative risk of death overtime after coapplication of compounds. Cumulative relative risk (RR) of death overtime with simultaneous intraperitoneal (i.p.) injection of POX, PAM and NAC, and GSH and AA. The legends on the side are depicting the treatment groups. RR was estimated by Cox [23] analysis, adjusted for POX dose (high/low) for each of the time points examined (30 min and 1, 2, 3, 4, 24, and 48 h). Best protection was conferred by simultaneous PAM treatment only and poor protection was estimated for all non-enzymatic treatment alone. Efficacy of PAM was estimated to decrement when co-administered with antioxidants.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4488549&req=5

fig1: Cumulative relative risk of death overtime after coapplication of compounds. Cumulative relative risk (RR) of death overtime with simultaneous intraperitoneal (i.p.) injection of POX, PAM and NAC, and GSH and AA. The legends on the side are depicting the treatment groups. RR was estimated by Cox [23] analysis, adjusted for POX dose (high/low) for each of the time points examined (30 min and 1, 2, 3, 4, 24, and 48 h). Best protection was conferred by simultaneous PAM treatment only and poor protection was estimated for all non-enzymatic treatment alone. Efficacy of PAM was estimated to decrement when co-administered with antioxidants.
Mentions: The relative risk of death at the seven time points (30 min, 1, 2, 3, 4, 24, and 48 h), estimated by Cox [23] analysis in simultaneous oxime and antioxidant-treated animals is depicted in Figure 1 and Table 3. Table 1 shows the percentage of mortalities at different time points of observation. RR was compared with untreated animals (Group 1, RR = 1) and adjusted for paraoxon dose (high/low). Statistical comparison was performed on the cumulative relative risk, that is, the area under the RR-time curve. Simultaneous pralidoxime treatment significantly reduced the paraoxon-induced mortality, RR; 0.33 ± 0.03 (P < 0.05) as compared to the no-treatment group (G1; paraoxon only). Simultaneous treatment of  NEAO yielded no significant protection. RR was 1.04 ± 0.04, 1.08 ± 0.03, and 0.85 ± 0.28 for NAC, GSH, and AA treatment, respectively. When antioxidants were administered together with PAM, AA treatment group produced statistically significantly higher mortality (RR 1.30 ± 0.12; P < 0.014) than no-treatment group, POX. NAC and GSH applied concurrently with PAM reduced the mortality in comparison with no-treatment group. Pattern of RR for pretreatment with antioxidants was almost the same as mentioned earlier (Figure 2, Tables 2 and 4); that is, only PAM pretreatment provided significant protection (RR 0.34 ± 0.03; P < 0.05). Antioxidant pretreatment without PAM yielded poor protection. RR estimated for NAC was 1.31 ± 0.24; GSH 0.93 ± 0.30; and AA 1.09 ± 0.33. The PAM efficacy was found to be decreased when animals were pretreated with antioxidants. RR values were 0.63 ± 0.15 for NAC, 0.93 ± 0.30 and 1.29 ± 0.0.18 for AA pretreatment, respectively, in comparison with RR 0.47 ± 0.17 for POX + PAM.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus