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Objective: To observe the effect of carbon disulfide (CS(2)) on the expression of matrix metalloproteinase (MMP)-2, MMP-9 in mouse embryo and uterus tissues and to explore the mechanism of embryo toxicity induced by CS(2)., Methods: At the phases of follicular development and embryonic implantation which was subdivided into early-implantation phase and late-implantation phase, mice were intraperitoneally exposed to CS(2) (the dosage was 631.4 mg/kg, and the volume was 0.1ml/10 g body weight) for 2 consecutive days. All indicators were got at the ninth day in gestation, and the expression of MMP-2 and MMP-9 in embryo and uterus tissues was analyzed by gelatin zymography., Results: The number of implanted embryos significantly decreased after exposure at late-implantation phase (16.000 ± 12.166) compared with those of the control (30.700 ± 5.599, P < 0.05). Expression of MMP-2 and MMP-9 in embryos declined obviously at the three reproductive phases (P < 0.01), and the levels of MMP-2 and MMP-9 expression in embryos at the phases of late-implantation phase (0.6837 ± 0.0929, 0.7309 ± 0.0822) and follicular development (0.6222 ± 0.0997, 0.7520 ± 0.1068) were much lower than those of the control (1.0000 ± 0.0710, 1.0000 ± 0.0413, P < 0.01). Expression of MMP-2 and MMP-9 in uterus significantly increased at the phase of late-implantation (1.3153 ± 0.3032, 5.0210 ± 4.0307) compared with those of the control (1.0000 ± 0.1771, 1.0000 ± 0.0996, P < 0.01)., Conclusion: Embryo toxicity of CS(2) is more obvious at the phase of late-implantation. Exposure to CS(2) disturbs expression of MMP-2 and MMP-9 in embryo and uterus tissues, which might be one of the important factors contributed to embryo toxicity induced by CS(2).

Ethnopharmacological Relevance: This study examined the protective effects of total saponins from Ornithogalum saundersiae (Liliaceae) on D-galactosamine (D-GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure., Materials and Methods: Total saponins of Ornithogalum saundersiae (Liliaceae) (OC) were prepared with ethyl alcohol extract from bulbs of the plant. Mice were given an intraperitoneal injection of D-GalN (700 mg/kg)/LPS (10 μg/kg). OC (100 mg/kg, 200 mg/kg and 300 mg/kg) was administered orally for 3 days continuously, and at the last day at 1 h before the D-GalN/LPS injection. Mice were sacrificed at 8 h after the D-GalN/LPS injection. The liver injury was assessed biochemically, investigating aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), glutathione (GSH) activities, and the expressions of caspase-3 and hypoxia inducible factor-1α (HIF-1α) as well. Tumor necrosis factor (TNF-α) content was measured after D-GalN/LPS induced 1 h by ELISA assay. The survival rates after application of OC in 24 h also were observed., Results: D-GalN/LPS increased the serum aminotransferase levels and lipid peroxidation, while decreased the reduced glutathione level. The pretreatment with OC attenuated these changes in a dose-dependent manner. Elevation of TNF-α level and activation of caspase-3, HIF-1α were observed in the D-GalN/LPS group, which was attenuated by OC. The survival rate of the OC groups was significantly higher than that of the D-GalN/LPS group., Conclusions: Protection afforded by OC against D-GalN/LPS-induced fulminant hepatic failure is the result of reduced oxidative stress, inhibited expression of caspase-3, HIF-1α, and anti-apoptotic activity., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The protective effect of a diterpenoid acanthoic acid (AA) isolated from Acanthopanax koreanum Nakai was investigated in acetaminophen (APAP)-induced hepatic toxicity. Drug-induced hepatotoxicity induced by an intraperitoneal (i.p.) injection of 300mg/kg (sub-lethal dose) of APAP. Pretreatment with AA (50 and 100mg/kg) orally 2h before the APAP administration attenuated the APAP-induced acute increase in serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activites, replenished the depleted hepatic glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities, decreased malondialdehyde (MDA) level and considerably reduced the histopathological alterations in a manner similar to silymarin (Sily). Immunohistochemical analyses also demonstrated that AA could reduce the appearance of necrosis regions as well as caspase-3 and hypoxia inducible factor-1alpha (HIF-1alpha) expression in liver tissue. Our results indicated that AA protected liver tissue from the oxidative stress elicites by APAP-induced liver damage and suggestes that the hepatic protection mechanism of AA would relate to antioxidation and hypoxia factor on APAP-induced hepatotoxicity., (Copyright 2009 Elsevier GmbH. All rights reserved.)

Aim: To investigate the in vivo hepatoprotective effects and mechanisms of Gentiana manshurica Kitagawa (GM) in acetaminophen (APAP)-induced liver injury in mice., Methods: GM (200, 150 or 50 mg/kg body weight) or N-acetyl-L-cysteine (NAC; 300 mg/kg body weight) was administrated orally with a single dose 2 h prior to APAP (300 mg/kg body weight) injection in mice., Results: APAP treatment significantly depleted hepatic glutathione (GSH), increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malonyldialdehyde (MDA) and 4-hydroxynonenal levels, and decreased hepatic activity of glutathione peroxidase (GSH-px) and superoxide dismutase (SOD). However, the pretreatment of GM significantly alleviated APAP-induced oxidative stress by increasing GSH content, decreasing serum ALT, AST and MDA, and retaining the activity of GSH-px and SOD in the liver. Furthermore, GM pretreatment can inhibit caspase-3 activation and phosphorylation of c-Jun-NH2-terminal protein kinase 2 (JNK1/2) and extracellular signal-regulated kinase (ERK). GM also remarkably attenuated hepatocyte apoptosis confirmed by the terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling method., Conclusion: Hepatoprotective effects of GM against APAP-induced acute toxicity are mediated either by preventing the decline of hepatic antioxidant status or its direct anti-apoptosis capacity. These results support that GM is a potent hepatoprotective agent.

Objectives: The aim was to investigate the protective effect of salidroside isolated from Rhodiola sachalinensis A. Bor. (Crassulaceae) on D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure., Methods: Hepatotoxicity was induced by an intraperitoneal injection of D-galactosamine (700 mg/kg) and lipopolysaccharide (10 mug/kg); salidroside (20, 50 and 100 mg/kg) was administered intraperitoneally 1 h before induction of hepatoxicity. Liver injury was assessed biochemically and histologically., Key Findings: Salidroside attenuated the induced acute increase in serum aspartate aminotransferase and alanine aminotransferase activities, and levels of tumour necrosis factor-alpha levels and serum nitric oxide. It restored depleted hepatic glutathione, superoxide dismutase, catalase and glutathione peroxidase activities, decreased malondialdehyde levels and considerably reduced histopathological changes. Histopathological, immunohistochemical and Western blot analyses also demonstrated that salidroside could reduce the appearance of necrotic regions and expression of caspase-3 and hypoxia-inducible factor-1alpha in liver tissue., Conclusions: Salidroside protected liver tissue from the oxidative stress elicited by D-galactosamine and lipopolysaccharide. The hepatoprotective mechanism of salidroside appear to be related to antioxidant activity and inhibition of hypoxia-inducible factor-1alpha.

Objective: To analyze the stress distribution in all-ceramic crowns when it was subjected to load., Methods: A 3D numerical model of the all-ceramic crown of the right mandibular first molar was generated from scanned CT images. Finite element analysis (FEA) was used to evaluate the stress distribution in the all-ceramic crown when it was subjected to 5 load conditions., Results: Stress distributions under 5 loading conditions were obtained. Stress concentrations were generally found near the loading areas at the veneer and at the lower surface of the core beneath the loading areas. In the 5 loading conditions, it was found that when the crown was loaded with vertical concentrated load, the tensile stresses around the shoulder areas were uniform, while stress concentration with maximum of 32.25 MPa was found at the shoulder areas in lingual-buccal direction when loads were applied at an angle of 10 degrees with the tooth axis on the buccal side. The masticatory load which was applied at 20 degrees with the tooth axis on the buccal side would cause stress concentration at the shoulder in mesial-distal direction. The maximum value could reach 11.29 MPa., Conclusions: The occlusal surface of the all-ceramic crown must be trimmed to increase multiple contact zones with the opposite surfaces in antagonist teeth to avoid excessive concentrated stress that may cause crown failure.

The purpose of this study was to explore the mechanism of CAG regimen eliminating T-cell acute lymphoblastic leukemia (T-ALL) A3 cell line and evaluate the role of G-CSF/G-CSFR system in this process. The expression levels of G-CSFR on the A3 cell membrane were detected by flow cytometry. Cell cycle changes of A3 cells treated with different concentrations of G-CSF for 48 hours were examined by propidium iodide staining method. The inhibition and apoptosis rates of A3 cells treated with various combinations of G-CSF, cytarabine (Ara-C), aclarubicin (ACR) were analyzed by Cell Counting Kit and AnnexinV Kit, respectively. The results indicated that the expression level of G-CSFR on A3 cells was 94.2%. The proportion of A3 cells in S-phase rose concomitantly with the increasing of G-CSF concentrations within 0-20 ng/ml. After incubation with Ara-C and G-CSF for 48 hours, A3 cells were inhibited more obviously compared with incubation with Ara-C alone (p<0.05, Ara-C 10(-5) mol/L and 10(-6) mol/L). After incubation with Ara-C, ACR and G-CSF for 48 hours, the apoptotic rate of A3 cells was much more than that after incubation with Ara-C and ACR. It is concluded that the expression level of G-CSFR on A3 cells is high, G-CSF/G-CSFR system has a synergetic effect on eliminating A3 cells when administrated simultaneously with chemical agents. This effect is caused through driving more cells from G0 phase into S phase, increasing sensitivity of A3 cells to chemical drugs and inducing cell apoptosis which may be one of the mechanisms of CAG regimen eliminating A3 cells.