Three 1,2,4-triazole derivatives B, D, and E were evaluated their effect on the activity of antioxidant enzymes glutathione peroxidase (GPX) and superoxide dismutase (SOD) in vivo serum and liver injury in mice that exposed to thioacetamide. Male rats of the present experiment were randomly divided into six equal groups. First group (C-) the animals were received normal saline as a negative control. Other five groups: C+ and T1-T4 exposed to oxidative stress by thioacetamide 100 mg/kg. The four animals' groups T1, T2, T3 and T4 were received thioacetamide 100 mg/kg and treated orally with 0.21 mg/kg daily with ascorbic acid (A), compound B, compound D and compound E, respectively. The experiment was carried out for eight weeks. The results indicated that the tested compounds exhibited remarkable antioxidant activity. The highest activity of SOD enzyme values was recorded of compound D 2665 IU/L compared to ascorbic acid as a standard antioxidant agent 1657 IU/L. On the other-hand the increasing in the activity of GPX enzyme value was recorded after administration of compound D 2010 IU/L compared to ascorbic acid as a reference antioxidant agent 1682 IU/L at the same conditions. Significant differences in the responses of antioxidant enzymes to the different types of tested compounds were probably due to by the variant number and site of functional group in structure of studied compounds. The results suggested that alteration in enzymes activities may be applicable to the capacity of the liver and other inspected organs to cope with oxidative stress poisoned thioacetamide. The results of current study concluded that compounds B and D appeared clear improvement in scavenging activity to modulate toxicity of thioacetamide and regeneration of hepatocyte as well as normalized body function. Altogether, the results that were obtained from the present study could lead to design of new potent molecules via development of them in future studies.

Prepare new derivatives 5-(3-Fluoro-biphenyl-2-yl)-7-nitro-1,3-dihydro-benzo[e] [1,4]diazepin-2-ol (88)and 5-Nitro-2’-(7-nitro-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)-biphenyl-3-carboxylic acid (89)compound from clonazepam and identified by spectrum of 13C-NMR and showed spectrum 1H-NMR . Clonazepam has massive adverse effect on prostate,lung,liver,kidney and spleen 3-new derivatives 5-(3-Fluoro-biphenyl-2-yl)-7-nitro-1,3-dihydro-benzo[e] [1,4]diazepin-2-ol (88) has limited effect and there is no clear changes in most organs studies.4-5-Nitro-2’-(7-nitro-2-oxo-2,3-dihydro-1Hbenzo[e][1,4]diazepin-5-yl)-biphenyl-3-carboxylic acid (89)compound has significant adverse effect but still less potent than clonazepam. OBJECTIVE To characterization and synthesis of new drugs related to clonazepam as well as to overcome massive adverse effect of clonazepam and increase the potency and half live of drugs.

This experiment was conducted to study effect of addition of garlic powder and cumin powderon blood picture and liver enzymes function in turkey, the experimental group randomly divided in to three groups as following: group one control the second and third group was given garlic powder and cumin powder respectively then, these groups were given garlic and cumin for aged 32 days in the drinking water at dose (2 g /5 liters). Blood samples were taken from each group at day 52, 72 respectively. The results showed significant increased at p < 0.05 for parameters of hematological analysis. There were significant (p> 0.05) differences between garlic and cumin groups with control to blood plasma GOT and GPT. There were significant increase in body weight at (p> 0.05).

An interaction toxicity study was performed to evaluate and compare the effect of P-glycoprotein (P-gp) inhibitor (captopril) and inducer (spironolactone) on their common substrate (lovastatin) that were done by comparing LD50 of the acute study with their chronic form then with those combined therapeutic doses administered for 90 days. Therefore, isobolographic analysis and chronicity index were used as the parameters for this study. Forty rats were allocated into five groups according to the used treatment into: captopril, spironolactone, lovastatin, captopril + lovastatin and spironolactone + lovastatin using up and down method to determine their acute exposure LD50 while ninety rats were used to perform the chronic stage of the study divided equally into six groups according to daily dosing regimen as following G1- control group administered distilled water orally; G2 administered captopril 0.7 mg/kg BW orally; G3-administered spironolactone 1.4 mg/kg BW orally; G4- administered lovastatin 0.57 mg/kg BW orally; G5-administered spironolactone1.4 mg/kg BW orally and lovastatin 0.57 mg/kg BW, G6- administered captopril 0.7 mg/kg BW and lovastatin 0.57 mg/kg BW orally. The results of isobolographic analysis showed that the sort of interaction between P-gp inhibitor (captopril) and lovastatin alone and as combined administration showed to be antagonistic after acute administration while it was synergistic after chronic administration; for P-gp inducer, spironolactone and lovastatin were additive after acute administration and antagonistic after chronic administration. Chronicity index results showed that both captopril and lovastatin accumulated after administered each alone and showed more accumulation after their combined administration while the chronicity index for P-gp inducer (spironolactone) and lovastatin showed less total concentration in the body burden after their combined administration than alone one. In conclusion, it seems that P-gp inhibitor (captopril) causes accumulation of itself and substrate (lovastatin), while P-gp inducer (spironolactone) causes reduction on the body burden of itself as well as lovastatin possibly due to their effects on the kinetics of the body and this may affect the efficacy and safety of drugs.