CP-2Chicago Pile 2 (Argonne Lab reactor)
CP-2Crystal Plaza 2 (Crystal City, Arlington, VA)
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G3, G4 and G5 received low dose (25 mg/kg, p.o.) of CP-1, CP-2 and CP-6, respectively; G6, G7 and G8 received high dose (50 mg/kg, p.o.) of CP-1, CP-2 and CP-6, respectively, G9 served as reference standard group and received atorvastatin (10 mg/kg p.o.).
The acute toxicity study involving intraperitoneal administration of CP-1, CP-2 and CP-6 at 55 and 175 mg/kg dose levels did not show any toxic signs during short term and long term observation periods.
The higher dose (50 mg/kg, p.o.) of CP-1, CP-2 and CP-6 treatments showed significant protection against dexamethasone-induced elevated serum cholesterol (p<0.01), triglyceride (p<0.01), LDL-C (p<0.01), VLDL-C (p<0.01) and the atherogenic index (p<0.01) in a statistically significant manner and HDL level (p<0.01) was maintained within the normal range and all the estimated biochemical parameters of the treated groups were comparable with the normal control group.
Pre-treatment with newly synthesized tricyclic benzothieno 1, 2, 3-triazine derivatives CP-1 (25 and 50 mg/kg p.o.), CP-2 (25 and 50 mg/kg p.o.), and CP-6 (25 and 50 mg/kg p.o.) showed significant protection against Triton WR-1339 induced hyperlipidemia at 6, 24 and 48 hours by preventing the elevation of serum cholesterol (p<0.01), triglycerides (p<0.01), LDL-C (p<0.01), VLDL-C (p<0.01) and maintaining the HDL-C levels (p<0.01) within the normal range (Tables 3, 4, 5).
Pretreatment with CP-1, CP-2 and CP-6 offered significant protection against dexamethasone-induced hyperlipidemia by maintaining serum cholesterol, triglycerides, LDL-C, VLDL-C and HDL-C nearly to normal levels and the atherogenic index was found to have significantly decreased compared to dexamethasone vis-a-vis the treated group.
In the present study, the anti-hyperlipidemic activities of atorvastatin and CP-1, CP-2 and CP-6 were evident in both synthesis and excretory phases of Triton WR-1339 induced hyperlipidemia in rats.
It is thought that CP-1, CP-2 and CP-6 are acting as anti-hyperlipidemic agents by inhibiting the biosynthesis of cholesterol and triglycerides and therefore can be used for the prevention (prophylactic) of hyperlipidemia; however, the drug-drug interaction of CP-1, CP-2 and CP-6 with dexamethazone and Triton WR-1339 can not be neglected and hence it may be a limitation of the present study.
These preliminary findings suggest that the newly synthesized triazine derivatives CP-1, CP-2 and CP-6 possess significant anti-hyperlipidemic activity against experimental animal models of hyperlipidemia.