OBJECTIVE: To find out the pathological change and the toxic mechanism of Chloranthus serratus Roem. et Schalt in mice. METHODS: Mice were intoxicated by oral administration with extracts of Chloranthus serratus Roem. et Schalt followed by pathological, serum biochemical, and coagulation mechanism examination. RESULTS: The LD50 in mice was 41.12 g/kg; All poisoned mice serum BUN and ALT increased markedly; Thrombocyte decreased and coagulation time increased; The organ index of liver, spleen and kidneys increased significantly; The cells of liver, kidney and heart were degeneration and necrosis, There were extensive hyperemia and hemorrhage in many organs. CONCLUSION The experiment suggests that the target organs were liver, kidney, heart and blood vessels; The toxic mechanism was the damage on the mitochondrional, endoplasmic reticulum and coagulation system.
Animals ; Biomarkers/blood* ; Dose-Response Relationship, Drug ; Endoplasmic Reticulum/drug effects* ; Female ; Forensic Pathology ; Kidney/pathology* ; Lethal Dose 50 ; Liver/pathology* ; Magnoliopsida/chemistry* ; Male ; Mice ; Mitochondria, Heart/drug effects* ; Mitochondria, Liver/drug effects* ; Myocardium/pathology* ; Plant Extracts/toxicity* ; Random Allocation

OBJECTIVETo reveal interventions for chronic cyclosporine A nephrotoxicity (CCN) and provide new targets for further studies, we analyzed all relevant studies about interventions in renal cell apoptosis.

DATA SOURCESWe collected all relevant studies about interventions for cyclosporine A (CsA)-induced renal cell apoptosis in Medline (1966 to July 2010), Embase (1980 to July 2010) and ISI (1986 to July 2010), evaluated their quality, extracted data following PICOS principles and synthesized the data.

STUDY SELECTIONWe included all relevant studies about interventions in CsA-induced renal cell apoptosis no limitation of research design and language) and excluded the duplicated articles, meeting abstracts and reviews without specific data.

RESULTSThere were three kinds of intervention, include anti-oxidant (sulfated polysaccharides, tea polyphenols, apigenin, curcumin, spirulina, etc), biologics (recombinant human erythropoietin (rhEPO), a murine pan-specific transforming growth factor (TGF)-beta-neutralizing monoclonal antibody1D11, cartilage oligomeric matrix protein (COMP)-angiopoietin-1 and hepatocyte growth factor (HGF) gene), and other drugs (spironolactone, rosiglitazone, pirfenidone and colchicine). These interventions significantly improved the CCN, renal cell apoptosis and renal dysfunction through intervening in four apoptotic pathways in animals or protected renal cells from apoptosis induced by CsA and increased cell survival through respectively four pathways in vitro.

CONCLUSIONSThere are three group interventions for CCN. Especially anti-oxidant drugs can significantly improve CCN, renal cell apoptosis and renal dysfunction. Many drugs can improve CCN through intervening in Fas/Fas ligand or mitochondrial pathway with sufficient evidences. Angiotensin II, nitric oxide (NO) and endoplasmic reticulum (ER) pathways will be new targets for CCN.

Animals ; Apoptosis ; drug effects ; Chronic Disease ; Cyclosporine ; adverse effects ; Humans ; Immunosuppressive Agents ; adverse effects ; Kidney ; drug effects ; pathology ; Mitochondria ; physiology ; Nitric Oxide ; physiology ; Signal Transduction ; fas Receptor ; physiology

OBJECTIVETo explore the effects of toosendanin in inducing apoptosis of human hepatocarcinoma cell line SMMC-7721 and Hep3B, and its influence on the related genes, Bcl-2, Bax and Fas.

METHODSThe inhibitory rate of cell proliferation and cell growth curve were detected by MTT assay; morphological changes of cells were observed by inverted microscope; early stage apoptosis rate were detected by Annexin V-FITC/PI assay; relative activities of Caspase-3,-8 and-9 were analyzed by spectrophotometry; and the expressions of Bcl-2, Bax and Fas were detected using immunohistochemistry assay.

RESULTSToosendanin presented significant inhibitory effect on proliferation of hepatocarcinoma cells in a time- and dose-dependent manner. After toosendanin treatment, the amount of cells was significantly reduced, shrunk in size and rounded in shape, with decreased adhesion ability. The apoptosis rates of SMMC-7721 cells and Hep3B cells treated with 0.5 micromol/L toosendanin for 72 h were 21.55% and 18.35% respectively, which were reduced after z-VAD-fmk (inhibitor of Caspase) treatment. The activities of Caspase-3,-8 and -9 all markedly enhanced after treatment in SMMC-7721 cells, while in Hep3B cells, activities of Caspase-3 and -9 enhanced, but that of Caspase-8 unchanged. As compared with the control group, after toosendanin treatment, expression of Bcl-2 decreased, and that of Bax and Fas increased in SMMC-7721 cells; but in Hep3B cells the expression of Bcl-2 decreased, that of Bax increased, and expression of Fas unchanged.

CONCLUSIONSToosendanin could inhibit the proliferation and induce the apoptosis of both P53 and P53 human hepatocarcinoma cells, which involved the participation of mitochondria-dependent pathway. So it may be a kind of natural anti-cancer drug, playing its effect through P53 independent pathway.

Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Mitochondria ; drug effects ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo investigate the effect of microtubule depolymerization on mitochondria damage in rat myocardiocytes early after hypoxia.

METHODSMyocardiocytes from Wistar rats were isolated according to routine procedure, and they were randomly divided into control group, depolymerization group (with treatment of 4 micromol/L colchicines in the culture medium), hypoxia group, hypoxia and depolymerization group (with treatment of 4 micromol/L colchicines in the culture medium combined with low oxygen tension). The changes in distribution of the mitochondria were examined with laser confocal microscopy, the morphology and the structure of mitochondria was observed by transmission electron microscope, the respiration control ratio (RCR) was determined by respirometer, and the content of adenosine triphosphate (ATP) in endochylema was detected with liquid chromatograph at 20, 30, 60 post-hypoxia minutes (PHM).

RESULTSIn control group, the mitochondria was in granular form, with regular arrangement, while mild changes were observed in depolymerization group. At 20, 30, and 60 PHM, the disarrangement in distribution and morphologic damage were aggravated in hypoxia depolymerization group, and the RCR (1.58 +/- 0.37, 1.51 +/- 0.32, 1.12 +/- 0.11, respectively) were evidently lower than those in hypoxia group (3.85 +/- 0.56, 2.98 +/- 0.44, 1.79 +/- 0.73, respectively, P < 0.01). The content of ATP showed the same tendency at the same time-points (419 +/- 83, 326 +/- 73, 295 +/- 58 ng/mg) compared with hypoxia depolymerization group [(475 +/- 68, 397 +/- 59, 336 +/- 67 ng/mg) in hypoxia group].

CONCLUSIONThe disarrangement in distribution of mitochondria, as well as the damage in mitochondrial structure, respiratory, function and energy metabolism, can be aggravated by microtubule depolymerization after hypoxia, which indicates that microtubule depolymerization plays an important role in the mitochondria damage.

Animals ; Cell Hypoxia ; Cells, Cultured ; Colchicine ; adverse effects ; Disease Models, Animal ; Hypoxia ; pathology ; Microtubules ; pathology ; Mitochondria, Heart ; drug effects ; pathology ; Random Allocation ; Rats ; Rats, Wistar

BACKGROUNDOxidative stress plays an important role in the pathogenesis of epidermal diseases. This study aimed to investigate the effects of quercetin on the anti-oxidative response and on mitochondrial protection in cultured normal human keratinocytes.

METHODSCultured HaCaT cells were treated with different concentrations of H2O2 (0, 50, 100, 250, 500 micromol/L) for different periods of time (0.5, 1, 2, 4 hours) to establish an oxidative stress model. The cultured HaCaT cells were randomly assigned to control, H2O2, and quercetin + H2O2 groups. For the quercetin groups, the cells were treated with different concentrations of quercetin (0, 10, 25, 50 micromol/L) before exposure to H2O2. Morphological changes of the cells were observed under an inverted microscope and an electron microscope. The cell viability was detected by the MTT method. The cell apoptosis (AnnexinV/propidium iodide double stain) and mitochondrial membrane potential (DeltaPsim) changes were detected by flow cytometry.

RESULTSAn oxidative stress model of HaCaT cells was established under a suitable concentration (250 micromol/L) and treated time of H2O2 (2 hours). The cell viability and DeltaPsim decreased in a concentration-dependent and time-dependent manner while the percentage of apoptotic cells significantly increased in the H2O2 groups compared with the control group (P < 0.05). The cell viability and DeltaPsim of the quercetin treated group increased (P < 0.05) and the percentage of apoptotic cells decreased at concentrations of 1-50 micromol/L quercetin (P < 0.01) compared with H2O2 treated group.

CONCLUSIONQuercetin can relieve the cell damage and apoptosis from H2O2 induced injury to HaCaT cells by anti-oxidation and mitochondrial protection.

Antioxidants ; pharmacology ; Apoptosis ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Humans ; Hydrogen Peroxide ; toxicity ; Keratinocytes ; drug effects ; pathology ; Membrane Potential, Mitochondrial ; drug effects ; Mitochondria ; drug effects ; Quercetin ; pharmacology

Baicalein, a flavonoid compound extracted from dried roots of traditional Chinese medicine Scutellaria baicalensis, has been widely applied as an antioxidant and anti-inflammatory agent. With continuous studies on its mechanisms, recent findings suggest that baicalein has some effect on neuroprotection and improvement of clinical symptoms in neurodegenerative diseases such as Parkinson's disease. Recent studies showed that its neuroprotective efficacy is closely related to such functions as antiinflammatory, antioxidative stress, protecting chondriosome, inhibiting glutamate neurotoxicity, promoting nerve growth and inhibiting alpha-synuclein protein-aggregate activities. The aim of this article is to summarize the neuroprotective effects of baicalein in Parkinson's disease.
Flavanones ; pharmacology ; therapeutic use ; Humans ; Mitochondria ; drug effects ; metabolism ; Nerve Growth Factor ; metabolism ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Oxidative Stress ; drug effects ; Parkinson Disease ; drug therapy ; metabolism ; pathology

OBJECTIVETo investigate the effect of Yishen Jiangzhuo Granules, YSJZG) on mitochondrial injury and regeneration and renal tubular epithelial cell apoptosis in chronic renal failure (CRF) rats and explore its mechanism from molecular pathology, gene, protein levels, and relative pathway.

METHODSThe CRF rat model was established using 5/6 nephrectomy. Sixty rats were randomly divided into six groups: sham-operation group, model (CRF) group, Niaoduqing Granules-treated group [5 g/(kg.day)], low-, moderate-, and high-dose [L-YSJZG, M-YSJZG, H-YSJZG at 3, 6, and 9 g/(kg day)] YSJZG-treated group (n=10 each). The levels of serum creatinine (Scr), blood urea nitrogen (BUN), and 24-h urine protein were assessed after 10 weeks of treatment. The tubulointerstitial injury and collagen deposition were evaluated using periodic acid-schiff stain and Masson staining. Renal tubular epithelial cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, mitochondrial injury was observed using an electron microscope, and superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were assessed using chromometry. Transforming growth factor-β1 (TGF-β1) expression was assessed using immunohistochemistry. The expressions of Bax, Bcl-2, peroxisome proliferator-activated receptor γ coactivator- 1α (PGC-1α), mitochondrial transcription factor A (Tfam), mitogen-activated protein kinases (MAPK) phosphorylation were evaluated by Western blot.

RESULTSYSJZG decreased the 24-h urine protein, BUN, Scr, remnant kidney weight-to-body weight ratio, renal tubular injury, deposition of collagen, and the apoptosis of renal tubular epithelial cells in a dose-dependent manner. YSJZG dose-dependently restored the number and structure of mitochondria and the expression of Tfam and PCG-1α, up-regulated the expression of Bcl-2, and inhibited the expression of Bax. YSJZG also dose-dependently inhibited TGF-β1 expression, increased SOD and GSH activity, decreased the MDA level, and inhibited p38MAPK and pERK1/2 phosphorylation (all P<0.01).

CONCLUSIONYSJZG improved the renal function in rats with CRF and inhibited the progression of tubulointerstitial fibrosis by dose-dependently alleviating mitochondrial injury, restoring the expression of Tfam and PCG-1α, and inhibiting renal tubular epithelial cell apoptosis through inhibiting activation of reactive oxygen species-MAPK signaling.

Animals ; Apoptosis ; drug effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Mitochondria ; drug effects ; Rats ; Rats, Sprague-Dawley ; Renal Insufficiency, Chronic ; drug therapy ; metabolism ; pathology

The ultrastructural alterations in rat liver by feeding NHM(nitrosohexamethylenemine). These are described at intervals of 10 days, 5 weeks, 11 weeks, 14 weeks, 19 weeks, and 22 weeks. The group at 5 and 11 weeks showed hyperplastic lesions but, no nuclear change. There were dilated rough endoplasmic reticulum with detached ribosomes, and alteration of mitochondria. The mitochondria showed a dense matrix which often included membranous materials. In the l4, 19, and 22 week groups, it showed nodular lesion which had atypical cells, and it was observed that the nucleus were enlarged and nucleoli were segregated. The bile canaliculi were dilated and contained dense materials.
Animal ; Female ; Liver/drug effects* ; Liver/pathology ; Methenamine/pharmacology* ; Microscopy, Electron ; Mitochondria, Liver/drug effects ; Nitrosamines/pharmacology ; Nitroso Compounds/pharmacology* ; Rats

OBJECTIVETo study the effect of chromomycin A(2) in inducing apoptosis of HepG2 cells and explore the molecular mechanism.

METHODSHepG2, MCF-7, A549, and 7901 cells were exposed to chromomycin A(2) and the changes in the cell viability were detected using MTT assay. The changes in the chromatins were observed with laser scanning confocal microscope after incubation of the cells with chromomycin A(2) (60 nmol/L) for 24 h. The changes in cell morphology were examined with a phase-contrast microscope, and the apoptotic cell populations, fluorescent intensity of reactive oxygen species (ROS) and mitochondrial membrane potential were determined using flow cytometry.

RESULTSChromomycin A(2) significantly inhibited the proliferation of the cells in a time- and dose-dependent manner, and caused changes in the cell morphology and cell apoptosis. Exposure of the cells to chromomycin A(2) resulted in chromatin condensation, ROS generation, and reduction of the mitochondrial membrane potential.

CONCLUSIONIncreased ROS and mitochondria damage may importantly contribute to chromomycin A(2)-induced apoptosis in HepG2 cells.

Apoptosis ; drug effects ; Cell Survival ; Hep G2 Cells ; drug effects ; Humans ; Membrane Potential, Mitochondrial ; Mitochondria ; pathology ; Plicamycin ; analogs & derivatives ; pharmacology ; Reactive Oxygen Species ; metabolism

OBJECTIVETo investigate the influence of pinacidil preconditioning on the protection of the structure and respiratory function of injured myocardial mitochondria in scalded rats.

METHODSSeventy-five healthy Wistar rats, weighed 250 approximately 300 g, were randomly divided into three groups: i.e. control (n = 9, with intraperitoneal injection of 50 microg/kg isotonic saline), scald (n = 33, with 30% TBSA full thickness scald) and pre-conditioning (n = 33, with same extent of scald injury after intraperitoneal injection of 50 microg/kg pinacidil) groups. Mitochondrial ultrastructure was observed by transmission electron microscope. The mitochondrial respiratory function, the MDA content and the superoxide anion level were determined with corresponding methods.

RESULTSThe degree of injury to rat myocardial mitochondria in pre-conditioning group was less intensive than that in scald group (P < 0.05 or 0.01). The respiratory control rate in pre-conditioning group was obviously higher than that in scald group (P < 0.05), and the contents of MDA and superoxide anion in pre-conditioning group were markedly lower than those in scald group (P < 0.05 or 0.01), as evidenced by their contents at 3 post scalding hours (0.60 +/- 0.09 micromol/g and 0.127 +/- 0.020) were obviously lower than those in scald group (0.83 +/- 0.07 micromol/g and 0.169 +/- 0.015) (P < 0.01).

CONCLUSIONPinacidil preconditioning was beneficial in the protection of myocardial mitochondria in scalded rats, and it might be related to the pre-opening of potassium channel which was sensitive to mitochondrial ATP.

Animals ; Burns ; drug therapy ; metabolism ; pathology ; Cell Respiration ; drug effects ; Disease Models, Animal ; Mitochondria, Heart ; metabolism ; pathology ; Pinacidil ; therapeutic use ; Rats ; Rats, Wistar ; Superoxides ; analysis