Anti-Platelet-Activating Factor Effects of Highly Active Antiretroviral Therapy (HAART): A New Insight in the Drug Therapy of HIV Infection?

被引:34
|
作者
Tsoupras, Alexandros B. [1 ]
Chini, Maria [2 ]
Tsogas, Nickolaos [2 ]
Fragopoulou, Elizabeth
Nomikos, Tzortzis [3 ]
Lioni, Athina [2 ]
Mangafas, Nikolaos [2 ]
Demopoulos, Constantinos A. [1 ]
Antonopoulou, Smaragdi [3 ]
Lazanas, Marios C. [2 ]
机构
[1] Univ Athens, Fac Chem, Athens, Greece
[2] Red Cross Gen Hosp, Dept Internal Med 3, Infect Dis Unit, Athens 11526, Greece
[3] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece
关键词
D O I
10.1089/aid.2007.0263
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Platelet-activating factor (PAF) is a potent inflammatory mediator, which seems to play a role in the pathogenesis of several AIDS manifestations such as AIDS dementia complex, Kaposi's sarcoma, and HIV-related nephropathy. PAF antagonists have been studied in these conditions with promising results. In order to examine the possible interactions between PAF and antiretroviral therapy, we studied the effect of nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors against PAF biological activities and its basic biosynthetic enzymes dithiothreitol-insensitive PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (Lyso-PAF-AT), as well as its main degradative enzyme PAF-acetylhydrolase, of human mesangial cell line (HMC). We also studied the effect of several backbones and highly active antiretroviral therapy (HAART) regimens against PAF activity. Among the drugs tested, several inhibited PAF-induced platelet aggregation in a concentration-depended manner, with tenofovir, efavirenz, and ritonavir exhibiting the higher inhibitory effect. In addition, when these drugs were combined in backbones and HAART regimens based on American antiretroviral therapy proposals, they also synergistically exhibited an inhibitory effect against PAF-induced platelet aggregation. Several of these drugs have also inhibited in vitro microsomal PAF-CPT activity, and concentrations of lopinavir-r or tenofovir-DF (similar to their IC50 against PAF-induced platelet aggregation) exhibited the same effect against PAF-CPT and Lyso-PAF-AT when added in the cell medium of cultured HMC. In addition, in naive patients treated with one of the most potent anti-PAF HAART regimens (efavirenz/emtricitabine/tenofovir-DF) for a period of 1 month, a significant reduction of the specific activity of PAF-CPT of washed human leukocytes of these patients was also observed, compared with its levels before the HAART treatment. These promising results need to be further studied and confirmed by additional in vivo tests in order to optimize HAART efficacy.
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收藏
页码:1079 / 1086
页数:8
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