[Show abstract][Hide abstract] ABSTRACT: Ovarian cancer presents therapeutic challenges due to its typically late detection, aggressive metastasis, and therapeutic resistance. The transcription factor Krüppel-like factor 4 (KLF4) has been implicated in human cancers as a tumor suppressor or oncogene, although its role depends greatly on the cellular context. The role of KLF4 in ovarian cancer has not been elucidated in mechanistic detail. In this study, we investigated the role of KLF4 in ovarian cancer cells by transducing the ovarian cancer cell lines SKOV3 and OVCAR3 with a doxycycline-inducible KLF4 lentiviral vector. Overexpression of KLF4 reduced cell proliferation, migration, and invasion. The epithelial cell marker gene E-cadherin was significantly upregulated, whereas the mesenchymal cell marker genes vimentin, twist1and snail2 (slug) were downregulated in both KLF4-expressing SKOV3 and OVCAR3 cells. KLF4 inhibited the transforming growth factor β (TGFβ)-induced epithelial to mesenchymal transition (EMT) in ovarian cancer cells. Taken together, our data demonstrate that KLF4 functions as a tumor suppressor gene in ovarian cancer cells by inhibiting TGFβ-induced EMT.
PLoS ONE 08/2014; 9(8):e105331. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the roles of oxygen free radicals and mitochondrial signaling in semen disorders, in particular, how this induces low concentrations and reduced motility of sperm. Ejaculate samples were obtained from 120 young adult males (mean age, 28.7±5.3 years) with normal semen (n=30), oligospermia (n=30), asthenospermia (n=30) and oligoasthenozoospermia (n=30). The malondialdehyde (MDA) content, total superoxide dismutase (T‑SOD) activity and glutathione peroxidase (GSH‑Px) activity of the sperm samples were determined by enzymatic assays. Mitochondrial membrane potential (MMP) was determined by flow cytometric detection of accumulated membrane‑permeable JC‑1 fluorescent dye. The mRNA and protein expression levels of apoptosis‑associated genes [Bcl‑2, Bax, cytochrome c (Cyt C) and caspase‑3] were measured by quantitative polymerase chain reaction and western blotting. Intergroup differences were evaluated by Student's t‑test. The sperm samples from all semen disorder groups exhibited significantly lower T‑SOD content and GSH‑Px activity (all P<0.05 versus normal sperm), and the extent of reduction revealed a disorder‑associated trend (asthenospermia < oligospermia ≈ oligoasthenozoospermia). By contrast, the semen disorder groups had significantly higher MDA content (all P<0.05 versus normal sperm); the extent of this increase also revealed a disorder‑associated trend (asthenospermia > oligospermia ≈ oligoasthenozoospermia). The sperm from patients with semen disorders also exhibited significantly lower MMP than normal sperm, as evidenced by lower mean ratios of JC‑1+ sperm per group. The semen disorder groups had significantly higher Bax, Cyt C and caspase‑3 mRNA and protein expression levels in the sperm samples, but significantly lower levels of Bcl‑2 (all P<0.05 versus normal sperm). However, only the extent of increases in Cyt C and caspase‑3 exhibited a disorder‑associated trend (oligospermia > asthenospermia). In conclusion, oxygen free radicals may be involved in reduced sperm concentration and motility, possibly through effects on the mitochondrial apoptotic signaling pathway. Perturbed mitochondrial release of Cyt C may be the distinguishing molecular feature between oligospermia and asthenospermia.
Molecular Medicine Reports 07/2014; · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Perinatal hypoxia-ischemia brain damage (HIBD) is a major cause of mortality and morbidity in neonates, and there is currently no effective therapy for HIBD. Carnosine plays a neuroprotective role in adult brain damage. We have previously demonstrated that carnosine pretreatment protects against HIBD in a neonatal rat model. Therefore, we hypothesized that treatment with carnosine would also have neuroprotective effects. Hypoxia-ischemia was induced in rats on postnatal days 7-9 (P7-9). Carnosine was administered intraperitoneally at a dose of 250mg/kg at 0h, 24h, and 48h after hypoxia-ischemia was induced. The biochemical markers of oxidative stress and apoptosis were evaluated at 72h after hypoxia-ischemia was induced, Brain learning and memory function performance were observed using the Morris water maze test on postnatal days 28-33 (P28-33). Treatment with carnosine post-HIBD significantly reduced the concentration of 8-iso-prostaglandinF2alpha in brain tissue and decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region and cortex as well as the mitochondria caspase-3 protein expression. Furthermore, carnosine also improved the cognitive function of P28-33 rats, whose cognitive function decline was due to HIBD. These results demonstrate that carnosine treatment after HIBD can reduce the brain injury, improving brain function. Carnosine could be an attractive candidate for treating HIBD.
European journal of pharmacology 01/2014; · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the prevalence of ureaplasma urealyticum (UU), mycoplasma hominis (MH), and chlamydia trachomatis (CT) infections among infertile and fertile men and to study the effects of these infections on semen quality.
A total of 621 infertile and 615 fertile men were enrolled in this study in our hospital between January 2011 and June 2013. Semen samples were obtained by masturbation after 3-5 days of sexual abstinence. Semen analysis was performed using the methods outlined by the World Health Organization. UU and MH were detected using culture, and CT was detected using polymerase chain reaction.
There were no significant differences between infertile and fertile men in terms of the prevalences of UU, MH, and CT. The presence of UU was related, in infected compared with uninfected men, to lower mean sperm concentration and lower vitality. The differences in semen parameters associated with MH or CT between infected and uninfected men did not attain statistical significance.
During the infertility assessment, the clinician should consider evaluating for the presence of UU in men with oligospermia or decreased sperm vitality.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the role of DiGeorge Critical Region 8 (DGCR8), a key component of miRNA biogenesis pathway in ovarian cancer.
The expression of DGCR8 in ovarian cancer was detected by immunostaining and DGCR8 knockdown in ovarian cancer cells was achieved using lentiviral shRNA. Differential expression of miRNAs was determined using Nanostring miRNA arrays and validated by real-time RT-PCR.
DGCR8 was highly expressed in ovarian cancer. Knockdown of DGCR8 expression inhibits cell proliferation, migration, and invasion, as well as sensitizes cells to apoptosis induced by the chemotherapeutic drug cisplatin. Cellular survival pathways including ERK1/2 mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT were attenuated in DGCR8 knockdown cells. DGCR8 knockdown results in dysregulated miRNA gene expression. miR-27b was identified as the most highly down-regulated miRNA in DGCR8 knockdown cells and promoted cell proliferation in ovarian cancer cells.
DGCR8 functions as an oncogene in ovarian cancer, which is in part mediated by miR-27b.
Pharmaceutical Research 10/2013; · 4.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Brachyury is a marker for notochord-derived tissues and neoplasms, such as chordoma. However, the prognostic relevance of brachyury expression in chordoma is still unknown. The improvement of tissue microarray technology has provided the opportunity to perform analyses of tumor tissues on a large scale in a uniform and consistent manner. This study was designed with the use of tissue microarray to determine the expression of brachyury. Brachyury expression in chordoma tissues from 78 chordoma patients was analyzed by immunohistochemical staining of tissue microarray. The clinicopathologic parameters, including gender, age, location of tumor and metastatic status were evaluated. Fifty-nine of 78 (75.64%) tumors showed nuclear staining for brachyury, and among them, 29 tumors (49.15%) showed 1+ (<30% positive cells) staining, 15 tumors (25.42%) had 2+ (31% to 60% positive cells) staining, and 15 tumors (25.42%) demonstrated 3+ (61% to 100% positive cells) staining. Brachyury nuclear staining was detected more frequently in sacral chordomas than in chordomas of the mobile spine. However, there was no significant relationship between brachyury expression and other clinical variables. By Kaplan-Meier analysis, brachyury expression failed to produce any significant relationship with the overall survival rate. In conclusion, brachyury expression is not a prognostic indicator in chordoma.
PLoS ONE 09/2013; 8(9):e75851. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: Interleukin-6 (IL-6) and its receptor complex participate in a number of critical biological activities through several signaling pathways. Placental dysfunction and increased inflammation are believed to underlie the pathogenesis of severe preeclampsia (PE), which may involve IL-6-induced signaling. We investigate whether the changes in the expression of IL-6 and its cognate receptors, IL-6 receptor (IL-6R) and glycoprotein (gp)130, occur between early and late onset severe PE. Methods: A total of 18 healthy gravidas and 41 severe preeclamptic women were recruited, including 20 pregnancies with early onset and 21 pregnancies with late onset. The IL-6, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130) levels in maternal and umbilical cord sera were tested by enzyme-linked immunosorbent assay; the immunoactivities of IL-6, IL-6R and gp130 in the placentas were determined by immunohistochemistry and immunoblotting. Results: We found that (1) maternal serum IL-6 and sIL-6R levels were increased, whereas sgp130 was decreased in women with early onset severe PE compared with those with late onset severe PE and normal controls. In contrast to normal controls, IL-6 and sIL-6R expression was up-regulated in late onset severe PE, and similar alterations of IL-6 and its soluble receptors were detected in early and late onset severe PE umbilical sera and (2) compared with late onset severe PE, reduced IL-6 and IL-6R but not gp130 expression was observed in early onset severe PE placentas. Conclusion: These results suggest a probable contributing role of alterations in IL-6 and its corresponding receptors to the pathophysiology of early and late onset severe PE.
Hypertension in Pregnancy 06/2013; · 0.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Preeclampsia complicates 5-10 % of pregnancies and is a leading cause of maternal/fetal morbidity and mortality. Although the cause is unknown, the reduced migration/invasion of extravillous trophoblasts is generally regarded as a key feature of preeclampsia genesis. The present study examined the expression of activator protein-2α (AP-2α), tissue inhibitor of metalloproteinase 2 (TIMP-2), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and E-cadherin in severe preeclamptic placentas and normal placentas using real-time PCR and immunohistochemistry. The expression levels of AP-2α, TIMP-2, and E-cadherin were elevated, while MMP-2 and MMP-9 levels were decreased in severe preeclamptic placentas when compared with normal placentas. To explore the underlying molecular mechanisms, BeWo cells were transfected with an AP-2α-expression construct as well as a siRNA against AP-2α. The over-expression of AP-2α decreased the invasive abilities of BeWo cells. AP-2α induction was followed by the induction of TIMP-2 and E-cadherin and a significant reduction of MMP-2 and MMP-9. Whereas in AP-2α-silencing BeWo cells, we observed the decreased expression of TIMP-2 and E-cadherin and the increased expression of MMP-2 and MMP-9. We presume that AP-2α may suppress trophoblast invasion by repression of MMP-2 and MMP-9 and up-regulation of E-cadherin, thus leading to shallow placentation in severe preeclampsia.
Molecular and Cellular Biochemistry 05/2013; 381(1-2). · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective Heat shock protein 70 (Hsp70), a highly conserved cellular stress protein, is produced in every organism from bacteria to man. The purpose of this study was to determine the difference in Hsp70 concentrations between term and preterm deliveries. Methods In total, 30 healthy term delivery and 99 preterm delivery (PD) women were recruited, including 46 women with preterm labor and intact membranes (PTL) with or without an intra-amniotic infection (IAI) and 53 women with a preterm premature rupture of membranes (PPROM) with or without IAI. The Hsp70 levels in the maternal and the umbilical cord sera were tested by an enzyme-linked immunosorbent assay (ELISA); the expression levels of Hsp70 in the placentas were determined by immunoblotting and real-time PCR. Results In contrast to the expression levels in normal term controls, Hsp70 expression levels were upregulated in preterm delivery; similar changes in Hsp70 expression levels were detected in preterm delivery maternal and umbilical sera. Patients with IAI were associated with a higher Hsp70 concentration than those without IAI. Conclusion These results suggest a probable contributing role of altered Hsp70 expression levels in the pathophysiology of preterm delivery.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 04/2013; · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTION: Preterm premature rupture of membranes (PPROM) is an obstetrics complication and is the leading cause of perinatal mortality and morbidity. PPROM results in critical care emergencies, and nearly all PPROM events are spontaneous and unpredictable. In addition, changes in the proteome in placental tissue during pregnancy that lead to PPROM are not clear. METHODS: We utilize a proteomics approach to study the molecular mechanisms behind human PPROM. A better understanding of proteome alteration could lead to the identification of better diagnostic/prognostic markers. Human placental tissue was collected in clearly differentiated cases of PPROM and in a healthy term control. Two-dimensional gel polyacrylamide electrophoresis coupled with mass spectrometry and bioinformatics analysis was utilized to identify proteins with altered expression. RESULTS: In this study, only the most important protein differences were selected for further analysis. Most of the identified proteins were structural/cytoskeletal components of the cell or involved in the regulation of energy metabolism and oxidative stress. CONCLUSIONS: As a result, this approach has led to the identification of several proteins involved in the underlying pathophysiological mechanisms that can further serve as novel diagnostic tools and targets for rational drug intervention.
Archives of Gynecology 04/2013; · 1.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: The aim of this study was to investigate the blood copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe), lead (Pb), and cadmium (Cd) concentrations in women of ≤12 (group I), 13-20 (group II), 21-27 (group III), 28-35 (group IV), and 36-42 (group V) weeks of gestation and compare them with those in nonpregnant women. DESIGN AND METHODS: The cross-sectional study was performed in 2380 pregnant women [group I (n=550); group II (n=552); group III (n=600); group IV (n=553); and group V (n=125)] and 552 nonpregnant women as controls. Blood seven elements concentrations, including Cu, Zn, Ca, Mg, Fe, Pd, and Cd, were determined by atomic absorption spectrometry (AAS). RESULTS: Compared with the nonpregnant women group, the concentrations of Cu, Zn, Ca, Mg, Fe, Pb, and Cd at ≤12, 13-20, 21-27, 28-35, and 36-42weeks of gestation, on the whole, were significantly different. Blood Cu, Mg, Ca, Fe, Pb, and Cd concentrations were correlated with weeks of gestation (P<0.05). The gestational age-specific reference intervals were established for Cu, Zn, Ca, Mg, Fe, Pd, and Cd. CONCLUSIONS: The established reference intervals for Cu, Zn, Ca, Mg, and Fe can provide important guidance for the reasonable supplementation of essential elements in pregnancy. And the reference intervals for Pd and Cd can play an important part in the surveillance and diagnosis of environmental overexposure.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Beta-catenin is a key nuclear effector of Wnt signaling which could be antagonized by dickkopf-1(DKK1). Beta-catenin and DKK1 are involved in a variety of biological processes; however, their expression in the placenta with severe preeclampsia (PE) has not been elucidated. This study was aimed to detect the localization and compare the expression of beta-catenin and DKK1 in normal and preeclamptic placenta. METHODS: Sixty pregnant women who underwent cesarean section were enrolled in this study, including 30 healthy pregnant women in the control group and 30 preeclamptic women in the severe PE group. Real-time polymerase chain reaction (real-time-PCR) and western blot were employed to detect the beta-catenin and DKK1 mRNA and protein expression levels, respectively, and their locations were evaluated by immunohistochemistry (IHC). RESULTS: Our results indicated that beta-catenin and DKK1 were expressed predominantly in the syncytiotrophoblast and the extravillous trophoblast (EVT). The beta-catenin mRNA and protein expressions were significantly decreased, whereas the DKK1 significantly increased in preeclamptic placental tissues compared to normal placental controls. CONCLUSIONS: In conclusion, decreased beta-catenin expression, as well as DKK1 over-expression might be associated with the process of the pathogenesis of PE. Further studies would elucidate their exact roles in the pathogenesis of PE.
Reproductive Biology and Endocrinology 03/2013; 11(1):17. · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:The Wnt signaling pathway is a conserved pathway and plays a crucial role in regulating trophoblast functions. Abnormal expression of the Wnt pathway may result in the dysfunction of the trophoblast that can contribute to the pathogenesis of preeclampsia (PE). However, published data regarding the association between Wnt pathway and PE in human pregnancy is rare.Objective:The aims of this study were to investigate the expression pattern of Wnt2 and secreted frizzled-related protein 4 (sFRP4) in the third trimester human placenta and to evaluate the relationship between changes in placental Wnt2 and sFRP4 expression and severe PE.Methods:The expression of Wnt2 and sFRP4 in normal and severe PE placentas was examined using immunohistochemistry (IHC), real-time polymerase chain reaction, and Western blot.Results:Compared to the controls, the relative expression of Wnt2 messenger RNA was remarkably downregulated in the PE placentas, while there was no significant difference in sFRP4 between the 2 groups. The IHC indicated that Wnt2 and sFRP4 were expressed predominantly in the villous syncytiotrophoblast and the extravillous trophoblast, whereas Wnt2 in the control group showed higher staining intensity than in the PE group, and sFRP4 in the PE group had a higher staining intensity than in the control group. Furthermore, the results of the Western blots were consistent with the IHC.Conclusions:The Wnt signaling pathway was detected in human third trimester placentas, and the decreased placental expression of Wnt2 and increased placental expression of sFRP4 may be associated with the pathogenesis of severe PE.
[Show abstract][Hide abstract] ABSTRACT: Maternal deaths occur mostly in developing countries and the majority of them are preventable. This study analyzes changes in maternal mortality and related causes in Henan Province, China, between 1996 and 2009, in an attempt to provide a reliable basis for introducing effective interventions to reduce the maternal mortality ratio (MMR), part of the fifth Millennium Development Goal.
This population-based maternal mortality survey in Henan Province was carried out from 1996 to 2009. Basic information was obtained from the health care network for women and children and the vital statistics system, from specially trained monitoring personnel in 25 selected monitoring sites and by household survey in each case of maternal death. This data was subsequently reported to the Henan Provincial Maternal and Child Healthcare Hospital. The total MMR in Henan Province declined by 78.4%, from 80.1 per 100 000 live births in 1996 to 17.3 per 100 000 live births in 2009. The decline was more pronounced in rural than in urban areas. The most common causes of maternal death during this period were obstetric hemorrhage (43.8%), pregnancy-induced hypertension (15.8%), amniotic fluid embolism (13.9%) and heart disease (8.0%). The MMR was higher in rural areas with lower income, less education and poorer health care.
There was a remarkable decrease in the MMR in Henan Province between 1996 and 2009 mainly in the rural areas and MMR due to direct obstetric causes such as obstetric hemorrhage. This study indicates that improving the health care network for women, training of obstetric staff at basic-level units, promoting maternal education, and increasing household income are important interventional strategies to reduce the MMR further.
PLoS ONE 10/2012; 7(10):e47153. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Enhanced apoptosis of the cytotrophoblast in early pregnancy is associated with a high risk of preeclampsia. We and others have previously reported that the transcriptional factor, activator protein AP-2α, suppressed trophoblast migration and invasion. However, it is not clear whether AP-2α affects apoptosis in trophoblast cells and whether it regulates expression of apoptosis-related factors Bcl-2 and Bax. We analyzed the expression of AP-2α, Bcl-2 and Bax in placental tissues in severe preeclamptic pregnancies and normotensive pregnancies using immunohistochemistry and real time-PCR. Further, apoptosis was assessed by flow cytometric analysis in the human trophoblastic cell line, BeWo cells, in which AP-2α expression was transiently overexpressed or down-regulated by siRNA. There was significantly higher expression of AP-2α and Bax, but lower expression of Bcl-2 in severe preeclampsia placentas as compared to the control placentas. Overexpression of AP-2α in BeWo cells led to an increased rate of apoptosis, whereas apoptosis was decreased when AP-2α expression was reduced. Furthermore, overexpression of AP-2α increased Bax expression and decreased Bcl-2 expression, whereas down-regulation of AP-2α expression resulted in a decrease in Bax expression and an increase in Bcl-2 expression. AP-2α regulates expression of Bcl-2 and Bax and apoptosis in BeWo cells. These results suggest that AP-2α-mediated regulation of Bcl-2 and Bax regulation influences apoptosis which in turn leads to the pathogenesis of preeclampsia.
Journal of molecular histology 08/2012; · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Interleukin-6 (IL-6) is a multifunctional cytokine which plays an important role in a wide range of biologic activities in different types of cell including tumor cells. IL-6 is involved in the host immune defense mechanism as well as the modulation of growth and differentiation in various malignancies. These effects are mediated by several signaling pathways, in particular the signal transducer and transcription activator 3 (Stat3). There exists abundant evidence demonstrating that deregulated overexpression of IL-6 was associated with tumor progression through inhibition of cancer cell apoptosis, stimulation of angiogenesis, and drug resistance. Clinical studies have revealed that increased serum IL-6 concentrations in patients are associated with advanced tumor stages of various cancers (e.g., multiple myeloma, non-small cell lung carcinoma, colorectal cancer, renal cell carcinoma, prostate cancer, breast cancer and ovarian cancer) and short survival in patients. Therefore, blocking IL-6 signaling is a potential therapeutic strategy for cancer (i.e., anti-IL-6 therapy) characterized by pathological IL-6 overproduction. Preliminary clinical evidence has shown that antibody targeted IL-6 therapy was well tolerated in cancer patients. In this review, we detail the progress of the current understanding of IL-6 signaling pathway in cancer as well as an antibody targeted IL-6 therapy for human cancer.
Cancer Treatment Reviews 05/2012; 38(7):904-10. · 6.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Development of multidrug resistance (MDR) during chemotherapy is a fundamental obstacle associated with cancer care. Prior studies have identified (2-(4-methoxyphenyl)-4-quinolinyl)(2-piperidinyl)methanol (5) (NSC23925) to be a small molecule agent that reverses MDR in cancer cells. We synthesized all four isomers of 5 and analyzed them by liquid chromatography-mass spectrometry (LCMS). Structure-activity relationships for reversing MDR were evaluated. Isomer 11 demonstrated the most potent activity. 11 reversed MDR in several drug-resistant cell lines expressing Pgp, including ovarian, breast, colon, uterine, and sarcoma cancer. 11 resensitized these cell lines to paclitaxel, doxorubicin, mitoxantrone, vincristine, and trabectedin with no effect on cell sensitivity to cisplatin, topotecan, and methotrexate. 11 significantly enhanced in vivo antitumor activity of paclitaxel in MDR xenograft models, without increasing the level of paclitaxel toxicity. In conclusion, 11 and derivatives of this compound may hold therapeutic value in the treatment of MDR-dependent cancers.
Journal of Medicinal Chemistry 03/2012; 55(7):3113-21. · 5.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Reference intervals for clinically important elements in infants and children are rarely reported, despite their importance for accurate clinical decision-making. The exploration of such reference intervals is essential.
Seven elements, including copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe), lead (Pb), and cadmium (Cd), were analyzed on BOHUI 5100 and 2100 analyzers using blood samples from 4044 healthy infants and children.
Age- and sex-specific reference intervals were established for Cu, Zn, Ca, Mg, Fe, Pb, and Cd.
Established reference intervals for Cu, Zn, Ca, Mg and Fe can provide important guidance for the reasonable supplementation of trace elements and other essential elements in infants and children. Reference intervals for Pb and Cd can play a role in the surveillance and diagnosis of environmental overexposure.
[Show abstract][Hide abstract] ABSTRACT: Perinatal hypoxia-ischemia brain injury is a major cause of mortality and morbidity in neonates and lacks an effective treatment thus far. Carnosine has been demonstrated to play a neuroprotective role in the adult brain injuries. However, there is no information available concerning its neuroprotective role in the immature brains after hypoxia-ischemia insults. Therefore, we investigated whether carnosine could also confer neuroprotective effects in a neonatal rat hypoxia-ischemia model. Hypoxia-ischemia was induced in rats on postnatal day 7 (P7). Carnosine (250 mg/kg) was administered intraperitoneally, 30 min prior to hypoxia-ischemia induction. Morphological brain injury and biochemical markers of apoptosis and oxidative stress were evaluated 24 h after hypoxia-ischemia induction. Cognitive performance was evaluated by the Morris Water Maze test on P28-P33. We found that pretreatment with carnosine significantly reduced the infarct volume and the number of terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the hypoxia-ischemia brain. Carnosine also inhibited mRNA expression of apoptosis-inducing factor(AIF) and caspase-3, which was accompanied by an increase in superoxide dismutase(SOD)activity and a decrease in the malondialdehyde(MDA)level in carnosine-treated rats. Furthermore, carnosine also improved the spatial learning and memory abilities of rats declined due to hypoxia-ischemia. These results demonstrate that carnosine can protect rats against hypoxia-ischemia-induced brain damage by antioxidation.
European journal of pharmacology 06/2011; 667(1-3):202-7. · 2.59 Impact Factor