Effects of Asphodeline lutea Compounds on Toxicity Models in Isolated Rat Microsomes and Hepatocytes
Küçük Resim Yok
Tarih
2018
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
BENTHAM SCIENCE PUBL LTD
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Background: In the current study, we evaluate the possible in vitro hepatoprotective and antioxidant activity of Asphodeline lutea (L.) Rchb. dry root extract (ALE), and isolated from the same extract 2-acetyl-1,8-dimethoxy-3-methylnaphthalene (1). The potential of the main root compounds, chrysophanol (2) and caffeic acid (3), was studied as well. A model of non-enzyme lipid peroxidation (LPO) in isolated liver microsomes was induced by iron-ascorbic acid (Fe2+/AA) mixture and assessed by the quantity of malondialdehyde (MDA) -an LPO product. The incubation of the microsomes with ALE (1 mg/ml) and 1-3 (100 mu g/ml) resulted in a significant decrease in MDA production, compared to the Fe2+/AA incubated samples with 23% (ALE), 61 % (1), 62% (3), while classical hepatoprotector silymarin decreased the parameter with 64 %. Methods: Studied compounds showed some toxicity in isolated rat hepatocytes discerned by increased LDH leakage and MDA quantity, decreased cell viability and reduced glutathione (GSH) levels compared to the control (non-treated hepatocytes). Results: The antioxidant and hepatoprotective potential of 1-3 was observed in vitro against carbon tetrachloride (CCl4)-induced toxicity, where they normalize all the examined parameters pertur-bated by CCl4 administration. The effects of 1 are lower than 3 and silymarin, but were better than those of 2. Conclusion: On the basis of these results, we discuss a bidirectional potential of the assayed parameters that might be explained with naphthalene transformation in cytochrom P450-dependent oxidation by CYP3A. The lack of metabolism and bioactivation of CCl4 could explain the cytoprotective effects of 1-3. The pro-oxidant effects of 1 and 2, in in vitro models, could be due to naphthalene and anthraquinone bioactivation pathways involving toxic metabolites.
Açıklama
Anahtar Kelimeler
Microsomes, hepatocytes, malondialdehyde, Asphodeline lutea (L.) Rchb., anthraquinones, naphthalenes
Kaynak
LETTERS IN DRUG DESIGN & DISCOVERY
WoS Q Değeri
Q4
Scopus Q Değeri
Q3
Cilt
15
Sayı
3
