Mechanism of protective effects of Danshen against iron overload-induced injury in mice

Gao, Yanni; Wang, Na; Zhang, Ying; Ma, Zhihong; Guan, Peng; Ma, Jinlu; Zhang, Yuanyuan; Zhang, Xue‐Jing; Wang, Jiangyan; Zhang, Jianping; Chu, Li

doi:10.1016/j.jep.2012.10.060

Cited by 39 publications

(22 citation statements)

References 40 publications

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“…In the iron overload condition, the increased deposition of iron into the heart in the long term inevitably leads to chronic myocardial damage, which is commonly characterized by cardiomyocyte necrosis (disintegration), myocardial fibrosis, and consequently decreased body weight gain and increased the heart weight [ 6 , 56 ]. In our study, the capability of SM to remove iron in the iron-overloaded heart was demonstrated by the significantly decreased levels of iron deposits in the myocardium (Fig 2B and 2C ) and restored myocardial architecture ( Fig 2A ), consistent with our previous studies [ 37 , 39 ]. More importantly, fibrotic cardiac tissue areas were also progressively diminished by administration of low and high doses of SM, while iron levels declined.…”

Section: Discussionsupporting

confidence: 91%

“…As a commonly used Chinese herbal medicine for cardiovascular diseases, SM has been demonstrated to have anti-fibrotic effects in vitro , in vivo and in clinical applications [ 48 – 51 ]. Additionally, our previous studies have demonstrated the significant protective effects of SM on the liver, heart and kidney in acute iron-induced injury [ 37 – 39 ]. Therefore, we hypothesized that SM treatment may be an effective therapy for myocardial fibrosis in chronic iron overload cardiomyopathy.…”

Section: Discussionmentioning

confidence: 99%

“…These studies suggest that SM may be beneficial in the treatment of cardiac iron-overload-induced fibrosis. Our previous studies also demonstrated the multi-targeted role of SM injection in decreasing iron deposition and inhibiting fibrotic development in iron-overloaded livers [ 36 , 37 ]. SM injection, an aqueous extract of SM, is a commercially available agent prepared according to the unified standard issued by the Ministry of Health of China and is commonly prescribed to treat cardiovascular, hepatic and renal diseases [ 38 ].…”

Section: Introductionmentioning

confidence: 97%

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Continuing Treatment with Salvia miltiorrhiza Injection Attenuates Myocardial Fibrosis in Chronic Iron-Overloaded Mice

et al. 2015

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Iron overload cardiomyopathy results from iron accumulation in the myocardium that is closely linked to iron-mediated myocardial fibrosis. Salvia miltiorrhiza (SM, also known as Danshen), a traditional Chinese medicinal herb, has been widely used for hundreds of years to treat cardiovascular diseases. Here, we investigated the effect and potential mechanism of SM on myocardial fibrosis induced by chronic iron overload (CIO) in mice. Kunming male mice (8 weeks old) were randomized to six groups of 10 animals each: control (CONT), CIO, low-dose SM (L-SM), high-dose SM (H-SM), verapamil (VRP) and deferoxamine (DFO) groups. Normal saline was injected in the CONT group. Mice in the other five groups were treated with iron dextran at 50 mg/kg per day intraperitoneally for 7 weeks, and those in the latter four groups also received corresponding daily treatments, including 3 g/kg or 6 g/kg of SM, 100 mg/kg of VRP, or 100 mg/kg of DFO. The iron deposition was estimated histologically using Prussian blue staining. Myocardial fibrosis was determined by Masson’s trichrome staining and hydroxyproline (Hyp) quantitative assay. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and protein expression levels of type I collagen (COL I), type I collagen (COL III), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) were analyzed to investigate the mechanisms underlying the effects of SM against iron-overloaded fibrosis. Treatment of chronic iron-overloaded mice with SM dose-dependently reduced iron deposition levels, fibrotic area percentage, Hyp content, expression levels of COL I and COL III, as well as upregulated the expression of TGF- β1 and MMP-9 proteins in the heart. Moreover, SM treatment decreased MDA content and increased SOD activity. In conclusion, SM exerted activities against cardiac fibrosis induced by CIO, which may be attributed to its inhibition of iron deposition, as well as collagen metabolism and oxidative stress.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Continuing Treatment with Salvia miltiorrhiza Injection Attenuates Myocardial Fibrosis in Chronic Iron-Overloaded Mice

et al. 2015

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“…injection of iron dextran as reported previously [18]. The serum levels of BUN and CR can be used as an index for renal dysfunction and damage.…”

Section: Discussionmentioning

confidence: 86%

“…The mechanism for some of its observed activities may be related to inhibition of LTCC [16] and prevention of Ca 2+ overload [17]. In particular, our recent study demonstrated that Danshen injection could significantly prevent iron overload-induced damage in the mouse liver [18], [19].…”

Section: Introductionmentioning

confidence: 93%

Danshen (Salvia miltiorrhiza) Injection Suppresses Kidney Injury Induced by Iron Overload in Mice

Guan

Zhang

et al. 2013

PLoS ONE

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ObjectivesExcessive iron can accumulate in the kidney and induce tissue damage. Danshen (Salvia miltiorrhiza) injection is a traditional Chinese medicinal preparation used for preventing and treating chronic renal failure. The aim of the present study was to evaluate the effects of treatment with Danshen injection on iron overload-induced kidney damage.MethodsMice were mock-treated with saline (control group) or given a single dose of iron dextran without treatment (iron overload group, 50 mg/kg/day for 2 weeks) or with daily treatments of low-dose Danshen (3 g/kg/day), high-dose Danshen (6 g/kg/day) or deferoxamine (100 mg/kg/day).ResultsTreatment of iron-overloaded mice with Danshen injection led to significant improvements of body weight and decreased iron levels in the kidney. Danshen injection treatment also reduced concentrations of blood urea nitrogen, creatinine and malondialdehyde and enhanced glutathione peroxidase and superoxide dismutase activities. Histopathological examinations showed that Danshen injection ameliorated pathological changes and reduced iron deposition in kidneys of iron overloaded mice. Furthermore, the treatment was demonstrated to suppress apoptosis in nephrocytes.ConclusionsThese results indicated that Danshen injection exerted significant renal protective effects in iron-overloaded mice, which were closely associated with the decrease of iron deposition and suppression of lipid peroxidation and apoptosis in the kidney.

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Diatom Chaetoceros Sp. as an Efficient Biological Antidote in Iron Toxicity: In‐Vitro and In‐Vivo Experiments

Janahmadi,

Talebi,

Farjadian

et al. 2024

ChemistrySelect

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All living organisms require mineral iron, but excess iron can lead to the production of free radicals and organ damage, such as liver damage in humans. This study investigated the diatom Chaetoceros sp. as an iron adsorbent in iron overload. First, the morphology and chemical composition of the diatom was characterized by spectroscopic and microscopic techniques. It was defined that diatoms have spherical particles with an average size of less than 2.0 μm. The affinity of diatoms for ionic Fe (II) uptake was evaluated. Fe (II) adsorption capacity was determined in vitro in two simulated intestinal and gastric aqueous media with pH values of 7.2 and 1.2. In both media, the diatom acted as a super‐adsorbent of Fe (II), while the highest adsorption occurred in a medium with a pH of 1.2. The correlation of the adsorption isotherm data was well studied with three well‐known equations, Langmuir, Fruindlich, and Redlich‐Peterson. The Langmuir model fitted the adsorption data best. The pseudo‐first‐order reaction model also provided a good fit for the adsorption kinetic data. In the in vivo study, the diatom was administered to iron‐overloaded rats. Biochemical parameters of organ damage and plasma Fe levels were determined at 2 h and 24 h intervals after diatom administration. The results show that diatoms can prevent acute iron poisoning by reducing plasma levels. Diatoms proved to be potent antidote agents in iron overdose conditions.

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Mechanism of protective effects of Danshen against iron overload-induced injury in mice

Cited by 39 publications

References 40 publications

Continuing Treatment with Salvia miltiorrhiza Injection Attenuates Myocardial Fibrosis in Chronic Iron-Overloaded Mice

Continuing Treatment with Salvia miltiorrhiza Injection Attenuates Myocardial Fibrosis in Chronic Iron-Overloaded Mice

Danshen (Salvia miltiorrhiza) Injection Suppresses Kidney Injury Induced by Iron Overload in Mice

Diatom Chaetoceros Sp. as an Efficient Biological Antidote in Iron Toxicity: In‐Vitro and In‐Vivo Experiments

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