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Comprehensive analysis of the effects of ordinary nutrients on hepatitis C virus RNA replication in cell culture.

Antimicrobial agents and chemotherapy (2007-04-11)
Masahiko Yano, Masanori Ikeda, Ken-Ichi Abe, Hiromichi Dansako, Shogo Ohkoshi, Yutaka Aoyagi, Nobuyuki Kato
ABSTRACT

To date, only a limited number of studies have reported finding an influence of ordinary nutrients on hepatitis C virus (HCV) RNA replication. However, the effects of other nutrients on HCV RNA replication remain largely unknown. We recently developed a reporter assay system for genome-length HCV RNA replication in hepatoma-derived HuH-7 cells (OR6). Here, using this OR6 assay system, we comprehensively examined 46 nutrients from four nutrient groups: vitamins, amino acids, fatty acids, and salts. We found that three nutrients-beta-carotene, vitamin D(2), and linoleic acid-inhibited HCV RNA replication and that their combination caused additive and/or synergistic effects on HCV RNA replication. In addition, combined treatment with each of the three nutrients and interferon alpha or beta or fluvastatin inhibited HCV RNA replication in an additive manner, while combined treatment with cyclosporine synergistically inhibited HCV RNA replication. In contrast, we found that vitamin E enhanced HCV RNA replication and negated the effects of the three anti-HCV nutrients and cyclosporine but not those of interferon or fluvastatin. These results will provide useful information for the treatment of chronic hepatitis C patients who also take anti-HCV nutrients as an adjunctive therapy in combination with interferon. In conclusion, among the ordinary nutrients tested, beta-carotene, vitamin D(2), and linoleic acid possessed anti-HCV activity in a cell culture system, and these nutrients are therefore considered to be potential candidates for enhancing the effects of interferon therapy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
cis-4,7,10,13,16,19-Docosahexaenoic acid, ≥98%
Sigma-Aldrich
(+)-α-Tocopherol, Type VI, from vegetable oil, liquid (≥0.88M based on potency, density and molecular wt.), BioReagent, suitable for insect cell culture, ≥1000 IU/g
Sigma-Aldrich
(+)-α-Tocopherol, from vegetable oil, Type V, ~1000 IU/g
Sigma-Aldrich
Ergocalciferol, ≥98.0% (sum of enantiomers, HPLC)
Sigma-Aldrich
Arachidonic acid, >95.0% (GC)
Sigma-Aldrich
Arachidonic acid, from non-animal source, ≥98.5% (GC)
Sigma-Aldrich
Ergocalciferol, 40,000,000 USP units/g
Sigma-Aldrich
Sodium selenate, BioXtra
Sigma-Aldrich
Sodium selenate, ≥95% (elemental analysis)
Sigma-Aldrich
Vitamin D2 solution, 100 μg/mL in ethanol, 98% (CP)
Sigma-Aldrich
L-Ascorbic acid, FCC, FG
Sigma-Aldrich
Linoleic acid, liquid, BioReagent, suitable for cell culture
Sigma-Aldrich
L-Ascorbic acid, BioXtra, ≥99.0%, crystalline
Sigma-Aldrich
L-Ascorbic acid, suitable for cell culture, suitable for plant cell culture, ≥98%
Sigma-Aldrich
L-Ascorbic acid, powder, suitable for cell culture, γ-irradiated
Sigma-Aldrich
Retinol, synthetic, ≥95% (HPLC), crystalline
Sigma-Aldrich
L-Ascorbic acid, ACS reagent, ≥99%
Sigma-Aldrich
β-Carotene, synthetic, ≥95% (HPLC), crystalline
Sigma-Aldrich
L-Ascorbic acid, reagent grade
Sigma-Aldrich
L-Ascorbic acid, suitable for plant cell culture
Sigma-Aldrich
L-Ascorbic acid, reagent grade, crystalline
Sigma-Aldrich
L-Ascorbic acid, meets USP testing specifications
Sigma-Aldrich
β-Carotene, synthetic, ≥93% (UV), powder
Sigma-Aldrich
L-Ascorbic acid, 99%
Sigma-Aldrich
L-Ascorbic acid, puriss. p.a., ACS reagent, reag. ISO, Ph. Eur., 99.7-100.5% (oxidimetric)
Supelco
L-Ascorbic acid, analytical standard
Sigma-Aldrich
Linoleic acid, technical, 58-74% (GC)
Sigma-Aldrich
L-Ascorbic acid, BioUltra, ≥99.5% (RT)
Sigma-Aldrich
L-Ascorbic acid, puriss. p.a., ≥99.0% (RT)
Supelco
Linoleic acid, analytical standard