| Co-Investigator(Kenkyū-buntansha) |
KONNO Kunio Johnan General Hospital, Director (the late), 院長
SUZUKI Hideo Tsukuba Res.Institute, Toa Gosei Chemical Industry, Director, つくば研究所, 所長 (50013321)
TAKAHASHI Kazuhiko Nagoya City University, Fac.of Pharmaceutical Sciences, Instructor, 薬学部, 講師 (40117833)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
A class of synthetic lignins (dehydrogenation polymers of p-coumaric acid, ferulic acid, and caffeic acid) inhibited cytopathogenicity of HIV-1 and HIV-2 infection. The polymers inhibited expression of HIV-specific antigen in the intected cells and also inhibited HIV-binding to the cells, but not completely, even at doses that almost completely inhibited the HIV-induced cytopathogenic effect. These results suggest that lignin structure, regardless of whether synthetic or natural, may inhibit HIV replication by an unidentified process, and thus prove to be a new class of anti-HIV agents possibly effective in the treatment of AIDS.
After the dehydrogenation polymer of p-coumaric acid, a synthetic lignin, was intravenously injected into mice, the serum was collected immediately, 15 min, 1 h, 5 h, and 24 h after the injection. The serum thus obtained was added to the assay medium containing MT-4 cells infected with HTLV-IIIB (an HIV-1 strain). Inhibition of the cytopathogenicity of HIV by these serum preparations was assayd by the MTT method. The result revealed that lignins could be a promising class of anti-HIV agents with an unidentified unique mode of action.
For safety assessment on genotoxicity, lignins and related compounds were tested for mutagenicity in Salmonella typhimurium tester strains and none of the compounds examined were proved to be mutagenic. This paper also describes a preliminary result on their antimugtagenic property ; synthetic and some natural lignins suppressed to a remarkable extent mutagenicities of 2-nitrofluorene and 1-nitropyrene, but not those of AF-2 and 4-nitroquinoline 1-oxide. In addition, they inactivated the S9 enzyme resulting in suppression of mutagenicity of Trp-P1, Trp-P2, and Glu-P1.
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