Role of prostaglandin H synthase in activation of acrylonitrile to cyanide

The present study aimed at investigating the in-vitro oxidation of acrylonitrile [ACN] to cyanide [CN] by prostaglandin H synthase [PHS]. Detection of CN is considered a marker for free radical intermediates involved in ACN-induced toxicity. First, most favorable circumstances for ACN oxidation were characterized: pH [4.5], temperature [37 degree C] and time of incubation [60 min.]. In addition, the concentrations of ACN, PHS and H2O2 in incubation mixtures were assessed for further reaction characterization. The reaction maximum velocity [Vmax] was calculated to be 582.75 pmol CN/mL/min and the Michaelis-Menten constant [Km] was 149.25 µmol ACN. Adding PHS inhibitors; resveratrol, quercetin, indomethacin or troloc-C to the reaction mixtures significantly reduced the rate of ACN oxidation. In conclusion, the present study demonstrates the ability of PHS to oxidize ACN to CN and provides a clue for the explanation of ACN target toxicity

In vitro and in vivo antioxidant activities of certain Egyptian plant extracts

Ethanolic extracts of 15 selected Egyptian plants belonging to 11 families were assessed in vitro as potential antioxidants using DPPH [1,1-diphenyl-2-picrylhydrazyl] free radical scavenging method. The highest activities were obtained from the extracts of Pelargonium graveolens L., Ceratonia siliqua L., Eucalyptus globulus Labill. and Psidium guajava L. The antioxidant activity of these extracts was evaluated in vivo by measurement of different parameters such as alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, superoxide dismutase, malondialdehyde, reduced glutathione and glutathione peroxidase in serum and I or liver of carbon tetrachloride intoxicated rats. Furthermore, the total polyphenol content of these plants was determined using Folin-Ciocalteau colorimetric method. Bioassay guided fractionation of the active ethanolic extract of Ceratonia siliqua [EC[50] =8.89 [micro]g/ml] proved that the ethyl acetate fraction was the most active. This was further purified via polyamide, cellulose and sephadex LH-20 column chromatography. Antioxidant compounds were isolated and identified using UV, 'H-NMR and MS spectroscopic methods. The compounds were characterized as: acacetin-7-O-[beta]-D-glucopyranoside, quercetin-3-O-beta-D-xylopyranoside and gallic acid

Ameliorative effect on Nigella Sativa on aflatoxin B1-induced hepatotoxicity in rats

Nigella Sativa is traditionally known in Middle Eastern countries as "Habbat Al-Baraka". Nigella is most famous for the saying of the Prophet Muhammad, 'Hold on to use of the Blackseed, for it has a remedy for every illness except death. The aim of this study was to assess the protective effect of Nigella Sativa [N. sativa] on aflatoxin B1 [AFB1]-induced hepatotoxicity in rats. Adult male Sprague Dawley rats were orally administered of AFB1 [50 microg/kg, in 0.2 ml olive oil by gastric gavage] twice/ week for 8 weeks. The liver was isolated and processed for biochemical analysis. Changes in body weight were noted every week. Levels of markers indicative of hepatotoxicity such as aspartate aminotransferases [AST], alanine aminotransferases [ALT], gamma glutamyltransferase [gamma-GT] and alkaline phosphatase [ALP] were assessed in the serum. The levels of hepatic thiobarbituric acid reactive substance [TBARS] as index of lipid peroxidation and glutathione redox status were assayed. The enzyme activities of catalase, glutathione peroxidase [GSH-Px], glutathione reductase [GR], and glutathione-S-transferase [GST] were determined in the liver. The levels of serum AST, ALT, gamma-GT, and ALP were increased significantly in AFB1 injected group than the control group. The levels of hepatic GSH was significantly decreased while the oxidized form of GSH [GSSG] was significantly increased in AFB1 group. The leveis of hepatic TBARS in AFBt group war. significantly higher than control group. The activities of catalase, GSH-Px, GR and GST in liver tissues were significantly decreased in AFB1 group compared to their levels in controls. In rats which received N. sativa [4 9le body weight/day for 8 weeks] with AFBt, the levels of TBARS and GSSG in liver tissues were significantly reduced while GSH level and catalase, GSH-Px, GR, and GST activities were significantly increased compared to AF81 group. N. sativa administration per se did not cause any change compared to the controls. However concomitant treatment of N. sativa with AFB1 showed considerable decrease in levels of markers for hepatotoxicity compared to AFB1 treated group. it was concluded that AFB1 can induce hepatotoxicity in rats. Nigelia sativa treatment of rats could enhance liver enzymatic antioxidants systems and GSH redox status, which consequently reduce the hepatotoxicity and the oxidative stress markers in the liver. Thus, clinical application of N. sativa as therapy should take a great attention in case of aflatoxicosis

Nitric oxide metabolites and antioxidants status in chronic obstructive pulmonary disease

The aim of this study was to determine the markers of nitric oxide [NO] metabolism [nitritelnitrate [NO2/NO3], nitrotyrosine and peroxynitrite inhibitory activity] in subjects with chronic obstructive pulmonary disease [COPD] and whether they correlate with oxidantlantioxidant system markers, which are glutathione [GSH], vitamin C and thiobarbituric acid reactive substance [TBARS]. Our results showed that, patients with COPD have a lower lung function than normal healthy control. Significant lower GSH levels were observed in the COPD group [3.22 +/- 1.06 micro mol/g Hb] compared with control group [4.83 +/- 1.03 micro mol/g Hb]. Also lower GSH levels were observed in smokers compared to nonsmokers in both groups. Mean levels of serum NO2/NO3 in patients with COPD [77.6 +/- 11.6 micro mol/L] were significantly higher than in healthy control group [26.42 +/- 8.4 micro mol/L] and also higher in smokers compared to nonsmokers. In contrast, peroxy nitrite inhibitory activity was significantly lowered in patients with COPD than normal controls [51.31 +/- 3.1 vs 94.3 +/- 7.1%, at p<0.001] and was also significantly correlated with FEV1 [r=0.591]. Moreover, there was a significant negative correlation between peroxynitrite inhibitory activity and NO2/NO3 levels in COPD patients [r=-0.716]. Nitrotyrosine concentrations were significantly increased in patients with COPD [54.7 +/- 5.2 ng/ml] compared with control group [8.36 +/- 0.71 ng/ml]. Lipid peroxidation levels were significantly higher in patients with COPD than in normal controls [2.01 +/- 0.80 vs 0.62 +/- 0.13 nmol/L]. TBARS levels were also significantly higher in smokers than nonsmokers. In contrast, vitamin C concentrations was significantly lower in patients with COPD than in normal controls [1.11 +/- 0.02 vs 2.19 +/- 0.31 mg/dl]. Our results showed a significant decrease in the peroxynitrite inhibitory activity, GSH and vitamin C and an increase in NO2/NO3, nitrotyrosine, and TBARS levels in patients with COPD compared to healthy controls which may provide some evidence for a potential role of increased NO metabolites production and decreased antioxidant activity in COPD especially in smokers