Acute and sub-chronic toxicity studies of Danshen injection in Sprague-Dawley rats

Wang, Meng; Jin, Lei; Zhou, Bo; Xu, Rui; Li, Tao; Ji, Meilin; Zhu, Liping; Jiang, Juan; Shen, Jiao; Gui, Xiaolong; Gu, Leilei; Bai, Wen-Xia; Sun, Wenguang; Cheng, Jiang

doi:10.1016/j.jep.2012.02.005

Cited by 31 publications

(26 citation statements)

References 19 publications

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“…Therefore, organ background data is particularly important because they not only can be used to determine whether treatment group animal organ weights are in the range of background data or not but also provide an important reference to provide to pathologists for gross anatomy and microscopic examinations 2 . In many institutes including our laboratory in China, CD(SD) (Sprague-Dawley) rats are used predominantly as experimental models in toxicity studies, and they have been used as traditional animal models for assessing carcinogenic potential of various kinds of compounds 3 . However, relatively few background data for organs weight from SD rats at different weeks of age are available.…”

Section: Introductionmentioning

confidence: 99%

Change Trends of Organ Weight Background Data in Sprague Dawley Rats at Different Ages

2013

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Organ weight is one of the most sensitive drug toxicity indicators, and its changes often precede morphological changes. So far, no background data about organ weight and its coefficient in SD rats at different weeks of age have been reported in China. The aim of this study was to summarize and analyze the change trends of organ weight and organ weight coefficients in SD rats at different weeks of age. The absolute of the weights of the brain, spleen, heart, lungs, liver, kidneys, adrenal glands and testes were increased in male SD rats from 13 to 78 weeks, and the weights of the brain, heart, lungs, liver, kidneys and especially the testes were decreased from 78 to 104 weeks. On the other hand, the absolute weight of the adrenal glands showed an increasing trend from 13 to 104 weeks. The absolute weight of the brain, spleen, heart, lungs, liver, kidneys, adrenal glands and ovaries showed an increasing trend from 13 to 104 weeks. A significant increase was observed in adrenal gland and ovary weights, whereas no obvious change trends were observed for the other organ weights mentioned above. It was surprising that the absolute of weight of the adrenal glands and organ-to-brain and organ-to-body weight ratios in female rats were significantly higher than those in males from 13 to 104 weeks. This study was the first to establish background data for organ weights in SD rats at different weeks of age and their reference ranges in line with the experimental animal status in China and to summarize their summarized their changes trend.

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Section: Introductionmentioning

confidence: 99%

Change Trends of Organ Weight Background Data in Sprague Dawley Rats at Different Ages

2013

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“…[17] It mainly contains water-soluble and bioactive phenolic acids, such as propanoid acid (PA), protocatechualdehyde (PHA), salvianolic acid B (SAB), salvianolic acid A (SAA), and rosmarinic acid (RA). [18] Although some researchers have indicated that Danshen injection possess low acute and sub-chronic toxicity,[19] more and more ADR cases induced by it are reported in the recent years. [20]…”

Section: Introductionmentioning

confidence: 99%

The stability investigation of compound Danshen injection (a traditional medicine) with a new high-performance liquid chromatography method

et al. 2013

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Background:Compound Danshen injection (CDSI, a traditional medicine) is an effective drug for the treatment of cardiovascular and cerebrovascular diseases. However, the research about its stability is absent.Objective:A new high-performance liquid chromatography method was developed to assay its main effective constituents, i.e., propanoid acid (PA), protocatechuic aldehyde (PHA), salvianolic acid B (SAB), salvianolic acid A (SAA), and rosmarinic acid (RA). Through the newly found method, the stability of CDSI was to be investigated.Materials and Methods:The analysis was performed by a reverse-phase gradient elution using an aqueous mobile phase (containing 0.1% acetic acid) modified by acetonitrile, and detection was made simultaneously at 280 nm and 325 nm. The method was validated for accuracy, precision and limits of detection. The effects of some environmental storage conditions (light and temperature) on the stability of CDSI were investigated.Results:This method is precise, simple, and convenient. The result showed that illumination and temperature had an obvious effect on CDSI's stability. SAA is the most unstable one among the five components. In the condition of common light, it decomposed rapidly to almost 50% after only 4 h, and 100% after 8 h. PA, RA, and PHA might come from Danshen, was also the transformed products from other components in store process.Conclusion:The result indicated that the main active constituents in CDSI suffered from the illumination and temperature greatly. CDSI should be stored at low temperature and kept away from light.

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“…The intravenous administration of the Danshen injection used in human clinical ap- plication has occurred for about forty years without major adverse reactions reports [26,27]. According to the study by Wang et al [28], the no-observed-adverse-effect-level of Danshen injection dose was 5.76 g • kg −1 body weight per day in rats which is about 1.92 times the high dose in the present mouse experiment based on the body surface area conversion for dose translation formula across species [29]. Danshen injection containing bioactive compounds, such as salvianic acid A, protocatechuic aldehyde, and salvianolic acid B, is widely used for the treatment of various cardiovascular conditions [30,31].…”

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confidence: 99%

Salvia miltiorrhiza (Danshen) Injection Ameliorates Iron Overload-Induced Cardiac Damage in Mice

Zhang

et al. 2013

Planta Med

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The traditional Chinese medicinal herb Danshen (Salvia miltiorrhiza), first recorded in the "Shen Nong's Herbal Classic", has long been used to treat cardiovascular conditions, although the mechanism(s) underlying its effects remain unclear. Here, an iron dextran injection (50 mg · kg⁻¹ per day) was delivered intraperitoneally to establish a mouse model for investigating the ameliorative effects of Danshen injection (low dose at 3 g · kg⁻¹ per day or high dose at 6 g · kg⁻¹ per day) on iron overload-induced cardiac damage. The iron-chelating agent deferoxamine (100 mg · kg⁻¹ per day) was administered as a positive control. The main constituents of Danshen injection, salvianic acid A (danshensu), protocatechuic aldehyde, and salvianolic acid B, were quantified at concentrations of 2.15, 0.44, and 1.01 mg · mL⁻¹, respectively, using HPLC with UV detection. Danshen injection significantly lowered cardiac iron deposition and the concentration of the lipid oxidation product malondialdehyde, as well as improved cardiac superoxide dismutase and glutathione peroxidase levels in iron-overloaded mice. Serum levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase in the iron-overloaded mice were significantly elevated (up to ~ 160 %), whereas their activities were downregulated by Danshen injection by 25 ~ 35 % at the high dose and by ~ 20 % at the low dose. Morphological changes of cardiac tissue analyzed by hematoxylin and eosin staining indicated that lesions induced by iron overload could be ameliorated by Danshen injection dose-dependently. Altogether, these results illustrated that the protective effects of Danshen injection were at least in part due to decreased iron deposition and inhibition of lipid peroxidation.

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Acute and sub-chronic toxicity studies of Danshen injection in Sprague-Dawley rats

Cited by 31 publications

References 19 publications

Change Trends of Organ Weight Background Data in Sprague Dawley Rats at Different Ages

Change Trends of Organ Weight Background Data in Sprague Dawley Rats at Different Ages

The stability investigation of compound Danshen injection (a traditional medicine) with a new high-performance liquid chromatography method

Salvia miltiorrhiza (Danshen) Injection Ameliorates Iron Overload-Induced Cardiac Damage in Mice

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