• The Korean Journal of Pharmacology
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• v.31 no.3
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• pp.345-353
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• 1995

${\beta}-Carboline$ alkaloids including harmaline have been shown to inhibit enzymatically or nonenzymatically induced-lipid peroxidation of microsomes. This study was done to explore the antioxidant ability of harmaline and harmalol on the oxidative injuries of hyaluronic acid, lipid and collagen by $Fe^{2+}$ and $H_2O_2$. Their scavenging actions on reactive oxygen species were also examined. Harmaline, harmalol, superoxide dismutase, catalase and DMSO inhibited both degradation of hyaluronic acid by $Fe^{2+}$ and $H_2O_2$ and lipid peroxidation of microsomes by $Fe^{2+}$. In these reactions, DABCO inhibited degradation of hyaluronic acid but did not affect lipid peroxidation. ${\beta}-Carbolines$ inhibited degradation of cartilage collagen by $Fe^{2+}$, $H_2O_2$ and ascorbic acid. The reduction of ferricytochrome c due to autoxidation of $Fe^{2+}$, which is inhibited by superoxide dismutase, was not affected by harmaline and harmalol. They also did not have a decomposing action on $H_2O_2$. Hydroxyl radical production in the presence of $Fe^{2+}$ and $H_2O_2$ was inhibited by harmaline, harmalol and DMSO. Harmaline and harmalol may inhibit the oxidative injuries of hyaluronic acid, lipid and cartilage collagen by $Fe^{2+}$ and $H_2O_2$ through their scavenging actions on reactive oxygen species, OH and probably iron-oxygen complexes and exert antioxidant abilities.

• Applied Chemistry for Engineering
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• v.32 no.5
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• pp.556-561
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• 2021

Recently, iron oxide nanoparticles have been used as the subject of many studies on drug delivery system (DDS) due to their excellent magnetic properties and biocompatibility in response to external magnetic fields. In this study, hyaluronic acid-superparamagnetic microneedles (HA-SMNs) and carboxy methyl cellulose-superparamagnetic microneedles (CMC-SMNs) containing superparamagnetic iron oxide nanoparticles (SIONs) were prepared with HA and CMC as a matrix materials of MNs (microneedles). Various properties of SMNs were then investigated with scanning electron microscopy (SEM), superconducting quantum interference device-vibrating sample magnetometer (SQUD-VSM), frequency mixing magnetic detection (FMMD), and polymer/bio membrane. The SQUID-VSM measurements showed superparamagnetism of HA-SMNs and CMC-SMNs containing SIONs. The FMMD results demonstrated that the signal intensity changed significantly as the concentration of SIONs increased. In addition, SMNs exhibited the average skin permeability intensities on the bio membrane for HA-SMNs and CMC-SMNs were 92.5 and 98.5%, respectively. These results suggested that SMNs could be utilized as deliver materials for a TDDS and MR molecular imaging.

• The Korean Journal of Pharmacology
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• v.21 no.1
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• pp.62-77
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• 1985

In tile Iron-catalyzed Haber-Weiss reaction to produce OH., the requirement for $O^{-}_{2}{\cdot}$ is only to reduce $Fe^{+++}$. Possibly, the role of $O^{-}_{2}{\cdot}$ can be replaced by other reducing agents. Ascorbate is one of them in biological system. In the present study, the ability of ascorbate to produce $OH{\cdot}$ in the presence of $Fe^{++}$ and $H_2O_2$ was investigated by observing the degradation of hyaluronic acid and ethylene production from methional. Ascorbate stimulated the degradation of hyaluronic by $Fe^{++}$ and $H_2O_2$. That was confirmed by both viscosity change and gel-permeation chromatographic analysis. The observed degradation was almost completely prevented by catalase and $OH{\cdot}$ scavengers. In support of the above results, ascorbate enhanced the prouction of ethylene from methional in the presence of $Fe^{++}$ and $H_2O_2$. Other reducing agents (cysteine, glutathione, NADH and NADPH) showed similar activities to ascorbate in the degradation of hyaluronic acid and ethylene production. But no stimulatory effects were observed with their oxidized forms such as NAD and NADP. Thus, it appears that reduction of the metal ion was needed for $OH{\cdot}$ production. Among the metal ions tested, $Fe^{++}$ showed most potent catalytic action in the production of $OH{\cdot}$ The results obtained support that ascorbate can substitute $O^{-}_{2}{\cdot}$ in the metal-catalyzed reactions, particularly with $Fe^{++}$ by which $OH{\cdot}$ is produced with $H_2O_2$. The significance of the ascorbate-dependent production of $OH{\cdot}$ was considered with respect to possible role of ascorbate in the damage of inflamed joints.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.111-118
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• 1998

Ambroxol is thought to have antioxidant ability and some antiinflammatory effect. Effect of ambroxol on the oxidative damages of lipid, collagen and hyaluronic acid was examined. F $e_{2+}$(10 $\mu$M) and 100$\mu$Mascorbate-induced lipid peroxidation of liver microsomes was inhibited by 10 and 100$\mu$M ambroxol, 30$\mu$g/ml catalase and 10 mM DABCO but was not affected by 30$\mu$g/ml SOD and 10 mM DMSO. A 10 and 100$\mu$M ambroxol and 10 mM DABCO inhibited the peroxidative action of 10$\mu$M F $e_{3+}$, 160$\mu$M ADP and 100$\mu$M NADPH on microsomal lipids, whereas inhibitory effects of 30$\mu$g/ml SOD,30$\mu$g/ml catalase and 10 mM DMSO were not detected. The degradation of hyaluronic acid caused by 107M Fe2\\`,5007M H2O2 and 100$\mu$M ascorbate was inhibited by 10 and 100$\mu$M ambroxol,30$\mu$g/ml catalase,10 mM DMSO and 10 mM DABCO, while 30$\mu$g/ml SOD did not show any effect. The cartilage collagen degradation caused by 307$\mu$ F $e_{2+}$,500$\mu$M $H_2O$$_2$ and 200$\mu$M ascorbate was prevented by 100$\mu$M ambroxol. $H_2O$$_2$ and OH . were scavenged by ambroxol, whereas $O_2$, was not removed by it. Ambroxol (100$\mu$M) and 1 mM cysteine reduced DPPH to 1,1-diphenyl-2-picrylhydrazine. In conclusion, ambroxol may inhibit the oxidative damages of lipid, hyaluronic acid and collagen by its scavenging action on oxidants, such as OH . and probably iron-oxygen complexes and exert antioxidant ability.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.6
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• pp.631-640
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• 1999

The present study investigated the stimulatory effects of iron (or ascorbate) on cyclosporine-induced kidney mitochondrial damage. Damaging effect of $50\;{\mu}M$ cyclosporine plus $20\;{\mu}M\;Fe^{2+}$ on mitochondrial lipids and proteins of rat kidney and hyaluronic acid was greater than the summation of oxidizing action of each compound alone, except sulfhydryl oxidation. Cyclosporine and $100\;{\mu}M$ ascorbate showed an enhanced damaging effect on lipids but not on proteins. The peroxidative action of cyclosporine on lipids was enhanced with increasing concentrations of $Fe^{2+}.$ Ferric ion $(20\;{\mu}M)$ also interacted with cyclosporine to stimulate lipid peroxidation. Damaging action of cyclosporine on mitochondrial lipids was enhanced by ascorbate $(100\;{\mu}M\;and\;1\;mM)$. Iron chelators, DTPA and EDTA, attenuated carbonyl formation induced by cyclosporine plus ascorbate. Cyclosporine $(100\;{\mu}M)$ and $50\;{\mu}M\;Fe^{2+}$ $(or\;100\;{\mu}M\;ascorbate)$ synergistically stimulated degradation of $2-{\alpha}$ deoxyribose. Cyclosporine $(1\;to\;100\;{\mu}M)$ reduced ferric ion in a dose dependent manner, which is much less than ascorbate action. Addition of $Fe^{2+}$ caused a change in absorbance spectrum of cyclosporine in $230{\sim}350$ nm of wavelengths. The results show that cyclosporine plus iron (or ascorbate) exerts an enhanced damaging effect on kidney mitochondria. Iron and ascorbate appear to promote the nephrotoxicity induced by cyclosporine.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.3
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• pp.295-305
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• 2021

Purpose: Hepcidin levels have previously been reported to be correlated with liver damage. However, the association between hepcidin levels and liver fibrosis in children with fatty liver disease remains unclear. This study therefore aimed to investigate the pathophysiology of fibrosis in children with fatty liver disease and its association with hepcidin levels. Methods: This retrospective case series included 12 boys aged 6-17 years who were diagnosed with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) at the Tokyo Medical University Hospital. Sixteen liver biopsy samples from 12 subjects were analyzed. Serum hepcidin levels were assayed using enzyme-linked immunosorbent assay. Immunostaining for hepcidin was performed, and the samples were stratified by staining intensity. Results: Serum hepcidin levels were higher in pediatric NAFLD/NASH patients than in controls. Conversely, a significant inverse correlation was observed between hepcidin immunostaining and Brunt grade scores and between hepcidin scores and gamma-glutamyltranspeptidase, hyaluronic acid, and leukocyte levels. We observed inverse correlations with a high correlation coefficient of >0.4 between hepcidin immunostaining and aspartate aminotransferase, alanine aminotransferase, total bile acid, and platelet count. Conclusion: There was a significant inverse correlation between hepcidin immunoreactivity and fibrosis in pediatric NAFLD patients; however, serum hepcidin levels were significantly higher, suggesting that these patients experienced a reduction in the hepcidin-producing ability of the liver in response to iron levels, leading to subsequent fibrosis. Therefore, hepcidin levels can be used as markers to identify the progression of fibrosis in patients with NAFLD.