1.Mechanism studies on hepatotoxicity of rats induced by Sophorae Tonkinensis Radix et Rhizoma in rat.
Fengjie LI ; Guangtao YAO ; Ruomin JIN ; Zheping SONG
China Journal of Chinese Materia Medica 2011;36(13):1821-1823
OBJECTIVETo study the hepatotoxicity mechanism of rats that induced by Sophorae Tonkinensis Radix et Rhizoma.
METHODThe SD rats were randomly divided into the control and Sophorae Tonkinensis Radix et Rhizoma (RRST) group, given distilled water and RRST 10 g x kg(-1) separately by orally for 7 days, and RRST 20 g x kg(-1) for other days until the 26th day. Blood was drawn from abdominal aorta after the rats were anesthetized by 25% urethane, and then centrifugally processed to get the serum for detection of ALT and AST. The liver tissues of control and experimental group were taken to prepare liver homogenate with cold NS, and centrifugally processed to get the supernatant. The activities of SOD and GSH, the content of gamma-GT and MDA were detected according to the methods of kit. The tumor necosis factor(TNF-alpha) was detected by ABC-ELISA. The expression of ICAM-1 was detected by immunohistochemistry.
RESULTAfter the rats were given RRST by oral for 26 days, the ALT and AST activities in serum increased, the content of GSH and the ratio of SOD and MDA decreased, the content of gamma-GT and TNF-alpha, the masculine expression of ICAM-1 increased.
CONCLUSIONAfter the rats were given RRST, the liver can be damaged obviously, and the mechanism of hepatotoxicity perhaps related to free radical and inflammatory factor.
Administration, Oral ; Alanine Transaminase ; metabolism ; Animals ; Aspartate Aminotransferases ; metabolism ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Female ; Free Radicals ; metabolism ; Glutathione ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Liver ; drug effects ; enzymology ; metabolism ; Male ; Malondialdehyde ; metabolism ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry ; Sophora ; chemistry ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; gamma-Glutamyltransferase ; metabolism
2.Effect of deltamethrin on production of free radical and transcription factor Nrf2 in rats' brain tissue.
Huang-yuan LI ; Nian SHI ; Si-ying WU ; Xin HUANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2009;27(10):593-596
OBJECTIVETo explore the effect of deltamethrin (DM) on production of free radical and transcription factor Nrf2 in rats' brain tissue.
METHODS8 male rats were randomly assigned to four groups and administered with 1% W/W tertiary butylhydroquinone (tBHQ) or olive oil for 3 days, prior to exposure to DM and then with 12.50 mg or 0mg DM/Kg BW for 5 days. The level of free radical in rats' hippocampus tissue was detected by electron spin resonance (ESR) spectroscopy. 18 male rats were randomly assigned to three groups and administered with i.p. (daily dose was respectively 0, 3.13, 12.50 mg/kg DM) for five days. After treatment, Nrf2 protein levels in the cytoplasmic and nuclear fractions of both cerebral cortex and hippocampus tissue were measured by western blot.
RESULTSThe level of free radical in hippocampus tissue of rats administered by DM and pretreatment with tBHQ prior to DM were increased to a 2.45-fold and 2.97-fold of values of control group, respectively (P < 0.05). Nrf2 protein levels in the cytoplasmic fractions of cerebral cortex of both low and high dose group were significantly increased, 1.68- fold and 1.34- fold of values of control group, respectively. Nrf2 protein levels in the nuclear fractions of cerebral cortex of both low and high dose group were increased in a dose- dependent model, 1.51-fold and 2.29-fold of values of control group, respectively (P < 0.01). Nrf2 protein levels in the cytoplasmic fractions of hippocampus tissue of both low and high dose group were increased in a dose- dependent model, 2.26-fold and 3.58-fold of values of control group, respectively. Nrf2 protein levels in the nuclear fractions of hippocampus tissue of both low and high dose group were increased, 2.42-fold and 2.45-fold of values of control group, respectively (P < 0.01).
CONCLUSIONThe studies in vivo demonstrate that DM treatment could induce free radical production and expression of Nrf2 protein in both cerebral cortex and hippocampus tissue and activate Nrf2.
Animals ; Brain ; drug effects ; metabolism ; Free Radicals ; metabolism ; Male ; NF-E2-Related Factor 2 ; metabolism ; Nitriles ; toxicity ; Pyrethrins ; toxicity ; Rats ; Rats, Sprague-Dawley
3.Antioxidative and cytotoxic properties of diarylheptanoids isolated from Zingiber officinale.
Leixiang YANG ; Changxin ZHOU ; Kexin HUANG ; Liyan SONG ; Qunxiong ZHENG ; Rongmin YU ; Rongping ZHANG ; Yihang WU ; Su ZENG ; Christopher H K CHENG ; Yu ZHAO ; Xiaokun LI ; Jia QU
China Journal of Chinese Materia Medica 2009;34(3):319-323
OBJECTIVETo investigate the antioxidant and cytotoxic properties of five diarylheptanoids (1-5) isolated from the rhizomes of Zingiber officinale.
METHODVarious models such as scavenging superoxide anions and 1,1-diphenyl-2- picrylhydrazyl (DPPH) radicals, inhibiting lipid peroxidation, as well as protecting of rat pheochromocytoma (PC12) cells induced by hydrogen peroxide (H2O2) were employed to assay the antioxidative effects of the diarylheptanoids. The cytotoxicities of compounds 1-5 were measured with MTT assays.
RESULTThe test compounds (1-5) showed promising DPPH inhibitory activities, and compound 5 exhibited the strongest DPPH scavenging activity with an IC50 value of (22.6+/-2.4) micromol x L(-1). Compounds 1, 3 and 4 showed potential anti-peroxidative effects with inhibitory rates of (66.3+/-15.4)%, (68.7+/-15.8)% and (72.2+/-10.6)%, respectively, at 100 microg x mL(-1). It could be observed that compounds 1, 3 and 4 demonstrated significant neuroprotective activities in a dose-dependent manner. Moreover, compound 3 exhibited certain cytotoxicities against human chronic myelogenous leukemia cells (K562) and its adriamycin-resistant cells (K562/ADR) with IC50 values of (34.9+/-0.6), (50.6+/-23.5) micromol x L(-1), respectively.
CONCLUSIONIn vitro results demonstrated that five diarylheptanoids (1-5) isolated from the roots of Z. officinale were capable of scavenging radicals, inhibiting lipid peroxidation and protecting PC12 cells against the insult by H2O2. Additionally, compound 3 could inhibit the growth of K562 and K562/ADR cells.
Animals ; Antioxidants ; toxicity ; Cell Proliferation ; drug effects ; Cytotoxins ; toxicity ; Diarylheptanoids ; isolation & purification ; metabolism ; toxicity ; Free Radicals ; metabolism ; Ginger ; chemistry ; Humans ; Hydrogen Peroxide ; metabolism ; K562 Cells ; Oils, Volatile ; pharmacology ; PC12 Cells ; Rats ; Rats, Sprague-Dawley
4.Antagonism effects of green tea against microcystin induced oxidant damage on liver and kidney.
Chuan XU ; Wei-Qun SHU ; Jia CAO ; Zhi-Qun QIU ; Qing ZHAO ; Ji-An CHEN ; Hui ZENG ; Wen-Juan FU
Chinese Journal of Preventive Medicine 2007;41(1):8-12
OBJECTIVETo evaluate the antagonism effects of green tea (GT) against microcystin LR (MC-LR) induced hepatotoxicity and nephrotoxicity in mice.
METHODSAll 40 male mice were randomly divided into four groups. Mice in group III and IV were pretreated with green tea for free drink at doses of 2 g/L and 12 g/L prior to MC-LR intoxication, for consecutively 18 days. The toxin treatment mice were administered continually intraperitoneal injections of MC-LR at a dose of 10 microg x kg(-1) x d(-1) bw from day 6th till sacrifice, continually 13 days. Mice were sacrificed and immediately subjected to necropsy, and the body weight, relative organ weight, serum biochemical parameters, antioxidant enzyme levels (SOD and GSH), lipid peroxidation products (MDA) and histopathology were systematically evaluated.
RESULTSMC-LR exposure led to increase the oxidative stress and organ injury was significantly observed through biochemical parameters and microscopic evaluation. However, high dose of GT pretreatment caused a significant elevation in serum GSH and SOD levels, and a decrease of serum MDA level as compared with MC-LR control. The mean values of GSH and SOD activities were separately 467.29 mg/L and 139.22 U/ml in group IV. Subsequently, GT pretreatment obviously diminished the serum ALT, AST and Cr activities. Those pathological damages in liver and kidney, were to a certain extent, lessened in GT pretreatment mice in correlation with the biochemical parameters.
CONCLUSIONGT might elevate antioxidant defense system, clean up free radicals, lessen oxidative damages and protect liver and kidney against MC-LR induced toxicity.
Animals ; Antioxidants ; pharmacology ; Chemical and Drug Induced Liver Injury ; Free Radicals ; metabolism ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Liver Diseases ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred Strains ; Microcystins ; toxicity ; Oxidative Stress ; Tea
5.Consumption of mercury-contaminated rice induces oxidative stress and free radical aggravation in rats.
Xiu-Ling JIE ; Gui-Wen JIN ; Jin-Ping CHENG ; Wen-Hua WANG ; Jing LU ; Li-Ya QU
Biomedical and Environmental Sciences 2007;20(1):84-89
OBJECTIVETo study the oxidative stress induced by consumption of mercury-contaminated rice in rats, and to assess the possible public health risk of mercury contamination in Wanshan mining area.
METHODSSprague Dawley rats were fed the mercury-contaminated rice produced from Wanshan area for 90 days. The antioxidant status and the free radicals in rat serum were evaluated.
RESULTSHigh mercury accumulation in organs of rats fed the mercury-contaminated rice confirmed the server pollution of mercury in Wanshan mining area. The intensity of electron spin resonance (ESR) signal increased by 87.38% in rats fed the rice from Wanshan compared with that in the control rats fed the rice from Shanghai, suggesting that chronic dietary consumption of rice from mercury mining area could induce an aggravation of free radicals. Feeding the mercury-contaminated rice was associated with significant decreases in the antioxidant enzymatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and concentration of serum nitric oxide (NO), but it had no effect on serum nitric oxide synthase (NOS) activity. Feeding the mercury-contaminated rice raised the level of serum malonyldialdehyde (MDA), indicating the occurrence of oxidative stress.
CONCLUSIONThe long-term dietary consumption of mercury-contaminated rice induces the aggravation of free radicals and exerts oxidative stress.
Animals ; Brain ; metabolism ; China ; Environmental Pollutants ; analysis ; pharmacokinetics ; toxicity ; Food Contamination ; analysis ; Free Radicals ; blood ; Glutathione Peroxidase ; blood ; Industrial Waste ; adverse effects ; Kidney ; metabolism ; Liver ; metabolism ; Malondialdehyde ; blood ; Mercury ; analysis ; pharmacokinetics ; toxicity ; Methylmercury Compounds ; analysis ; pharmacokinetics ; toxicity ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; Oryza ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood
6.Relationship between Pulmonary Surfactant Protein and Lipid Peroxidation in Lung Injury due to Paraquat Intoxication in Rats.
Hyo Wook GIL ; Mi Hae OH ; Kee Min WOO ; Eun Young LEE ; Myung Ho OH ; Sae Yong HONG
The Korean Journal of Internal Medicine 2007;22(2):67-72
BACKGROUND: Pulmonary damage resulting from lipid peroxidation is a principal effect of paraquat intoxication. The host-defense functions of surfactant are known to be mediated by the surfactant proteins A and D (SP-A and SP-D, respectively). The primary objective of this study was to evaluate the variations over time in levels of surfactant protein and lipid peroxidation (LPO) in lung tissue following free-radical-induced injury. METHODS: 42 adult, male, Sprague-Dawley rats were administered intraperitoneal injections of paraquat (35 mg/kg body weight). SP-A and SP-D levels were determined via Western blot. LPO in the left lung homogenate was measured via analyses of the levels of thiobarbituric acid-reactive substances. RESULTS: LPO levels peaked at 6 hours, with no associated histological changes. SP-D levels increased until hour 12 and declined until hour 48; SP-D levels subsequently began to increase again, peaking at hour 72. SP-A levels peaked at hour 6, declining thereafter. CONCLUSIONS: We suggest that in the early phase of paraquat injury, SP-D levels reflect alveolar damage and that de novo synthesis of SP-D takes 72 hours. Levels of SP-A, on the other hand, reflect abnormalities in the surfactant system in the late stage of paraquat intoxication. Surfactant proteins may play a role in protecting the lungs from reactive oxygen injury. A time-dependent variation has been observed in the levels of surfactant proteins A and D following paraquat injury, and it has been suggested that these proteins play a role in the protection of lung tissue against ROS-induced injuries.
Animals
;
Free Radicals/*toxicity
;
Herbicides/*toxicity
;
*Lipid Peroxidation
;
Lung/*drug effects
;
Male
;
Paraquat/*toxicity
;
Pulmonary Surfactant-Associated Proteins/*analysis
;
Rats
;
Rats, Sprague-Dawley
;
Reactive Oxygen Species/toxicity
;
Respiratory Distress Syndrome, Adult/*chemically induced
7.Effects of aqueous extract of Hedysarum austrosibiricum on metabolism of oxyen free radicals in subacute aging mice caused by D-galactose.
Taoerdahong HAILIQIAN ; Jin-sen KANG ; Lian SUN
China Journal of Chinese Materia Medica 2007;32(8):729-731
OBJECTIVETo investigate the anti-aging effect of aqueous extract of Hedysarum austrosibiricum cultivated in Xin-jiang.
METHODSubacute aging model in mice was established by D-galactose (D-gal) and activities of SOD and GSH-PX, contents of MDA in brain and liver tissues, activities of MAO in brain tissue and immune indexes were determined.
RESULTAqueous extract of H. austrosibiricum Xinjiang markedly increased the activities of SOD and GSH-PX, significantly decreased contents of MDA in brain and liver tissues. MAO activities in brain tissue were also decreased. It also elevated the spleen and thymus indexes.
CONCLUSIONAqueous extract of H. austrosibiricum might have anti-aging effect, which is implemented by eliminating oxyen free radicals, rising activities
Aging ; drug effects ; metabolism ; Animals ; Antioxidants ; isolation & purification ; pharmacology ; Brain ; drug effects ; metabolism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Fabaceae ; chemistry ; Female ; Free Radical Scavengers ; isolation & purification ; pharmacology ; Free Radicals ; metabolism ; Galactose ; toxicity ; Glutathione Peroxidase ; metabolism ; Liver ; drug effects ; metabolism ; Malondialdehyde ; metabolism ; Mice ; Monoamine Oxidase ; metabolism ; Plant Extracts ; isolation & purification ; pharmacology ; Plant Roots ; chemistry ; Random Allocation ; Superoxide Dismutase ; metabolism
8.Effects of AST and ASI on metabolism of free radical in senescent rats treated by HC.
Wei-Zu LI ; Wei-Ping LI ; Yan-Yan YIN
China Journal of Chinese Materia Medica 2007;32(23):2539-2542
OBJECTIVETo study the effects of Astragaloside (AST) and Astragalus Saponin I (ASI) on metabolism of free radical and immune function in senescent rats treated by HC.
METHODHydrocorisone (HC) was used to estabilsh the aging model in rats. The content of molondialdehyde (MDA), glutathoine (GSH) and oxidized glutathoine (GSSG) in liver and brain was detected according to kit. The activity of Mn superoride dismulase (Mn-SOD) and catalase (CAT) was also surveyed by kit. Concanavalin (ConA) was used to detect the proliferation and interleukin-2 (IL-2) production of splenocytes.
RESULTCompared with HC control, AST and ASI could decrease the content of MDA, GSH and GSSG in liver and brain, increase the activity of Mn-SOD and CAT, and promote the proliferation and interleukin-2 (IL-2) activity of splenocytes.
CONCLUSIONAST and ASI could delay the aging effect in rats treated by HC, and its mechanism maybe the antioxidant and regulating immunity.
Aging ; drug effects ; metabolism ; Animals ; Astragalus membranaceus ; chemistry ; Catalase ; metabolism ; Cell Proliferation ; drug effects ; Cerebral Cortex ; metabolism ; Female ; Free Radicals ; metabolism ; Glutathione ; metabolism ; Glutathione Disulfide ; metabolism ; Hydrocortisone ; toxicity ; Interleukin-2 ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Malondialdehyde ; metabolism ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Saponins ; isolation & purification ; pharmacology ; Spleen ; cytology ; Superoxide Dismutase ; metabolism ; Triterpenes ; isolation & purification ; pharmacology
9.Studies of chemical constituents and their antioxidant activities from Astragalus mongholicus Bunge.
De-Hong YU ; Yong-Ming BAO ; Chao-Liang WEI ; Li-Jia AN
Biomedical and Environmental Sciences 2005;18(5):297-301
OBJECTIVETo evaluate the antioxidant activities of different chemical constituents from Astragalus mongholicus Bunge and their protection against xanthine (XA)/xanthine oxidase (XO)-induced toxicity in PC12 cells.
METHODSThe compounds of Astragalus mongholicus Bunge were isolated by chromatography and the structures were elucidated on the basis of spectral data interpretation. Their antioxidant activities were detected by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities in a cell-free system. Meanwhile, the effects against XA/XO-induced toxicity were assessed using MTT assay in PC12 cells.
RESULTSTen principal constituents were isolated and identified as formononetin (I), ononin (II), calycosin (III), calycosin-7-O-beta-D-glucoside (IV), 9,10-dimethoxypterocarpan-3-O-beta-D-glucoside (V), adenosine (VI), pinitol (VII), daucosterol (VIII), beta-sitoster (IX) and saccharose (X) from Astragalus mongholicus Bunge. The compounds I, III, and IV scavenged DPPH free radicals in vitro. Formononetin and calycosin were found to inhibit XA/XO-induced cell injury significantly, with an estimated EC50 of 50 ng/mL.
CONCLUSIONCompound II, VI, and VII are first reported in this plant. Calycosin exhibits the most potent antioxidant activity both in the cell-free system and in the cell system.
Animals ; Astragalus Plant ; chemistry ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Free Radical Scavengers ; chemistry ; pharmacology ; Free Radicals ; metabolism ; Isoflavones ; chemistry ; pharmacology ; PC12 Cells ; Rats ; Xanthine ; toxicity ; Xanthine Oxidase ; toxicity
10.Astragalus membranaceus reduces free radical-mediated injury to renal tubules in rabbits receiving high-energy shock waves.
Bin-wu SHENG ; Xing-fa CHEN ; Jun ZHAO ; Da-lin HE ; Xun-yi NAN
Chinese Medical Journal 2005;118(1):43-49
BACKGROUNDRecent studies have revealed the important role of free radicals in renal damage induced by high-energy shock waves (HESW). This study aimed at investigating the effects of Astragalus membranaceus, a traditional Chinese medicinal herb, on free radical-mediated HESW-induced damage to renal tubules in a live rabbit model.
METHODSForty-five healthy male New Zealand white rabbits were randomly divided into three groups: control group (n = 15), sham group (n = 15), and herb-treated group (n = 15). Three days prior to HESW application, the controls received verapamil (0.4 mg/kg), the shams received physiological saline (20 ml), and the herb-treated animals received Astragalus membranaceus (2.4 g/kg) intravenously. HESW (1500 shocks, 18 kV) was applied to the right kidneys of all anesthetized rabbits. We measured superoxide dismutase (SOD) and malondialdehyde (MDA) levels before and after shock treatment in blood and kidney homogenates. Histopathological changes were also observed.
RESULTSMDA levels increased and SOD activity decreased significantly in the sham group (P < 0.05 for both) after shock treatment. MDA levels showed a much less increase in the controls (P < 0.05) and did not increase to statistically significant levels in the group receiving Astragalus membranaceus (P > 0.05). SOD values were significantly higher in the controls than in the shams (P < 0.05). By contrast, SOD levels recovered rapidly in the rabbits receiving Astragalus membranaceus, reaching a nadir within 24 hours, and returning to baseline more quickly than in control and sham rabbits (P < 0.05). Histopathological examinations showed that renal tubular damage in the controls was less severe than in the shams, while damage in the Astragalus membranaceus group was even more mild, with rapid recovery in comparison with the controls.
CONCLUSIONThis study provides preliminary evidence indicating that Astragalus membranaceus has strong protective effects on free radical-mediated renal tubular damage induced by HESW and that these effects are superior to the effects of verapamil.
Animals ; Astragalus membranaceus ; Free Radicals ; toxicity ; High-Energy Shock Waves ; adverse effects ; Kidney Tubules ; drug effects ; pathology ; Male ; Malondialdehyde ; blood ; Phytotherapy ; Rabbits ; Superoxide Dismutase ; blood ; Verapamil ; pharmacology

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