Metabolism and Cytotoxicity of Menadione and Its Metabolite in Rat Platelets

Effect of Compounds Isolated from Natural Products on IFN-γ/LPS–Induced Nitric Oxide Production in RAW 264.7 Macrophages

“…In contrast to the above observation, among the 12 anthraquinones studied, 1,4-dihydroxy-2,3-dimethoxylanthraquinone and morindone showed an enhancement rather than an inhibitory effect on NO production. It is interesting to note that although many quinones have been found to exhibit cytotoxic effects through the generation of reactive oxygen species via enzymatic redox cycle or the loss of protein thiols caused by arylation (Chung et al, 1997), atrovirinone, 1,4-dihydroxy-2,3-dimethoxylanthraquinone, and morindone did not show cytotoxic effects except at the highest concentration of 50 mM. However, atrovirinone at the lower concentration of 12.5 mM, had strong inhibitory activity on NO production without any cytotoxic effects.…”

Detection of Emodin Derived Glutathione Adduct in Normal Rats Administered with Large Dosage of Polygoni Multiflori Radix

“…The reactive metabolites covalently bind to intracellular nucleophiles such as amino acids, glutathione (GSH), proteins, and nucleic acids, thereby triggering a series of pathologic alterations and causing liver injury (James et al, 2003; Fu et al, 2004; Lin et al, 2011). In general, conjugation with GSH is a major detoxification route for many xenobiotics (Chung et al, 1997; Chen et al, 2009), since this conjugation reaction protects cells against the harmful effects of reactive metabolites. On the other hand, the overproduction of electrophilic reactive metabolites will deplete GSH and eventually produce the toxicity (Kouzi et al, 1994; Shimizu et al, 2011).…”

The biological significance of non‐enzymatic reaction of menadione with plasma thiols: enhancement of menadione‐induced cytotoxicity to platelets by the presence of blood plasma

“…One complication which should be considered was the binding of menadione to plasma protein which could cause substantial decreases in the concentration of free menadione. To compensate for this effect, we utilized previously observed data [20], which indicated that the free menadione concentration in PRP incubation solution containing 1 mM menadione was equivalent to the free menadione present in WP incubation solution containing 0.25 mM menadione. We therefore compared 1 mM menadione‐treated PRP with 0.25 mM menadione‐treated WP, as well as 0.25 mM menadione‐treated PRP with 0.25 mM menadione‐treated WP.…”

“…In addition, we compared toxicity to platelets using 1 mM menadione in PRP with 0.25 mM menadione in WP. This comparison was made because our previous paper [20] demonstrated that the concentration of free menadione in PRP with 1 mM menadione was equivalent to that of WP with 0.25 mM menadione. We demonstrated that greater and more rapid toxicity resulted from 1 mM PRP (Fig.…”