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Journal of Biochemical and Molecular Toxicology

Yuefeng Zhang, Risheng Huang, Weihe Zhou, Qifeng Zhao, Zhenye Lü
Myocardial ischemia/reperfusion (I/R) injury is a leading cause of morbidity and mortality. In this study, we investigated the role of miR-192-5p in hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis. H9c2 cardiomyocytes were subjected to H/R and tested for miR-192-5p expression. Overexpression and knockdown experiments were performed to determine the effects of manipulating miR-192-5p on apoptotic responses. H/R-treated H9c2 cells exhibited a 2.2-fold increase in miR-192-5p levels. Overexpression of miR-192-5p significantly augmented apoptosis in H9c2 cells after H/R, which was accompanied by a significant increase in the ratio of Bax/Bcl-2...
October 25, 2016: Journal of Biochemical and Molecular Toxicology
Mustafa Ceylan, Umit M Kocyigit, Necibe Canan Usta, Belma Gürbüzlü, Yusuf Temel, Saleh H Alwasel, İlhami Gülçin
Benzothiazepine compounds have a wide range of applications such as antibacterial, antidepressants, anticonvulsants, antihypertensives, antibiotics, antifungal, hypnotic, enzyme inhibitors, antitumor, anticancer and anti-HIV agents. In this study, the synthesis of novel tetralone-based benzothiazepine derivatives (1-16) and their in vitro antibacterial activity and human carbonic anhydrase isoenzymes I and II (hCA I and II) inhibitory effects were investigated. Both isoenzymes were purified by sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography from fresh human red blood cells...
October 25, 2016: Journal of Biochemical and Molecular Toxicology
Qing Chen, Xin Zhang, Jin-Yan Zhao, Xiao-Ning Lu, Peng-Sheng Zheng, Xiang Xue
The effects of paraquat (PQ) on the male reproductive system are unclear. In this study, male rats were divided into four groups (0, 0.5, 2, and 8 mg/kg) and treated with PQ by oral gavage for 8 weeks. At the end of the experiment, a significant decline in sperm count, motility, and viability and an increase in teratospermia were observed in the PQ-treated group (P < 0.05). Further investigation found that PQ resulted in enhanced lipid peroxidation and more apoptosis in the testis tissues, and apoptosis was likely to be associated with activation of the mitochondrial pathway...
October 20, 2016: Journal of Biochemical and Molecular Toxicology
Nishat Ahmed, Nada F Bakhashwain, Alaa F Alsehemi, Dina S El-Agamy
Vardenafil is a selective phosphodiesterase-5 inhibitor used for erectile dysfunction treatment. The hepatoprotective role of vardenafil against acute hepatitis is not reported yet. Hence, this study aims to explore the protective role of vardenafil against concanavalin A (Con A) induced acute liver injury. Mice were pretreated with vardenafil (0.17 mg/kg/day) for seven consecutive days, and then subjected to a single IV injection of Con A. The results demonstrated that the vardenafil pretreatment significantly reduced the elevated serum levels of transaminases and alkaline phosphatase...
October 20, 2016: Journal of Biochemical and Molecular Toxicology
Xiang Lin, Qing Wang, Xilin Peng, Hui Li
Metandienone (MET) is an exogenous anabolic androgenic steroid. The interaction between MET and human serum albumin (HSA) was investigated by molecular modeling and different optical techniques. There was no possibility of energy transfer, and the fluorescence quenching of HSA induced by MET was mainly due to the complex formation. The differences of binding ability between MET and compounds 1-5 were significantly caused by space steric hindrance. The single crystallographic data of two steroids (compounds 4 and 5) were obtained in the methanol at the first time...
October 20, 2016: Journal of Biochemical and Molecular Toxicology
Xiangbin Song, Zifa Li, Fei Liu, Zhenyong Wang, Lin Wang
Previous study has demonstrated that puerarin (PU) exerts nephroprotective effect against Pb-induced cytotoxicity in primary rat proximal tubular (rPT) cells. Autophagy can protect cells from various cytotoxic stimuli, but its role in the process of PU against Pb-induced nephrotoxicity is still unknown. This study aims to investigate whether PU can alleviate Pb-induced renal damage by recovering autophagy. Data showed that Pb inhibited the autophagic flux, as evidenced by the accumulation of LC3-II and p62 as well as the confocal microscopy analysis of GFP-LC3 puncta and punctate spots of monodansylcadaverine staining, whereas coadministration of PU could restore Pb-induced autophagy inhibition...
October 20, 2016: Journal of Biochemical and Molecular Toxicology
Hui Li, John D Clarke, Anika L Dzierlenga, John Bear, Michael J Goedken, Nathan J Cherrington
Nonalcoholic steatohepatitis (NASH) has been identified as a source of significant interindividual variation in drug metabolism. A previous ex vivo study demonstrated significant changes in hepatic Cytochrome P450 (CYP) activity in human NASH. This study evaluated the in vivo activities of multiple CYP isoforms simultaneously in prominent diabetic NASH mouse models. The pharmacokinetics of CYP selective substrates: caffeine, losartan, and omeprazole changed significantly in a diabetic NASH mouse model, indicating attenuation of the activity of Cyp1a2 and Cyp2c29, respectively...
October 6, 2016: Journal of Biochemical and Molecular Toxicology
Jun-Hui Choi, Seung Kim
Thrombosis is a leading cause of morbidity and mortality throughout the world. Thrombolytic agents are important for both the prevention and treatment of thrombosis. Fibrin clot and turbidity assays revealed that it was able to inhibit the formation of fibrin clot. Chlorogenic acid degraded blood clot and inhibited the enzymatic activity of procoagulant proteases, thrombin, activated factor X (FXa), and activated factor XIII (FXIIIa). Chlorogenic acid was found to delay activated partial thromboplastin time, prothrombin time, and thrombin time...
October 5, 2016: Journal of Biochemical and Molecular Toxicology
Ariadna B Juárez-Martínez, Rogerio R Sotelo-Mundo, Enrique Rudiño-Piñera
Glutathione S-transferases (GSTs) are dimeric proteins that play a key role in phase II cellular detoxification. Here, the first crystal structure of a GST class-mu from marine crustacean shrimp Litopenaeus vannamei is reported at a resolution of 2.0 Å. The coordinates reported here have the lowest sequence identity with previously reported GSTs class-mu deposited at the Protein Data Bank (PDB), although they have subtle conformational differences. One key feature of GST class-mu from L. vannamei is the active site crevice markedly reduced when it is compared with other GSTs class-mu...
September 22, 2016: Journal of Biochemical and Molecular Toxicology
Wei Qi Lee, Ida Syazwani M Affandi, Shevin R Feroz, Saharuddin B Mohamad, Saad Tayyab
Interaction of pendimethalin (PM) herbicide with the major transporter in human circulation, human serum albumin (HSA), was studied using fluorescence, circular dichroism (CD), and molecular modeling methods. The attenuation of the fluorescence intensity of HSA in the presence of PM revealed formation of the PM-HSA complex. Analysis of the fluorescence quenching data showed moderately strong binding affinity between PM and HSA. Both hydrophobic interactions and hydrogen bonding were suggested to stabilize the PM-HSA complex, based on thermodynamic data...
September 16, 2016: Journal of Biochemical and Molecular Toxicology
Nikita Joshi, Jessica L Ray, Anna K Kopec, James P Luyendyk
Exposure of rodents to the xenobiotic α-naphthylisothiocyanate (ANIT) is an established model of experimental intrahepatic bile duct injury. Administration of ANIT to mice causes neutrophil-mediated hepatocellular necrosis. Prolonged exposure of mice to ANIT also produces bile duct hyperplasia and liver fibrosis. However, the mechanistic connection between ANIT-induced hepatocellular necrosis and bile duct hyperplasia and fibrosis is not well characterized. We examined impact of two different doses of ANIT, by feeding chow containing ANIT (0...
September 8, 2016: Journal of Biochemical and Molecular Toxicology
Erika Rubí Luis-García, Jorge Humberto Limón-Pacheco, Norma Serrano-García, Alma Delia Hernández-Pérez, José Pedraza-Chaverri, Marisol Orozco-Ibarra
Quinolinic acid (QA) triggers striatal neuronal death by an excitotoxic cascade that involves oxidative stress, which in turns is tightly linked to mitochondria. Mitochondrial dysfunction is a molecular feature described in several brain pathologies. In this work, we determined whether the sulforaphane-neuroprotective effect in the rodent experimental model of Huntington's disease induced by QA is associated with mitochondrial function preservation. We found that QA impaired mitochondrial function within 24 h post-lesion...
September 2, 2016: Journal of Biochemical and Molecular Toxicology
Ahmad Salimi, Ehsan Gholamifar, Parvaneh Naserzadeh, Mir-Jamal Hosseini, Jalal Pourahmad
Mitochondria play an important role in myocardial tissue homeostasis; therefore, deterioration in mitochondrial function will eventually lead to cardiomyocyte and endothelial cell death and consequently cardiovascular dysfunction. Lithium (Li(+) ) is an effective drug for bipolar disorder with known cardiotoxic side effects. This study was designed to investigate the effects of Li(+) on mitochondria and cardiomyocytes isolated from the heart of Wistar rat. Results revealed that Li(+) induced a concentration- and time-dependent rise in mitochondrial ROS formation, inhibition of respiratory complexes (II), mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release in rat heart mitochondria and also induced Caspase 3 activation through mitochondrial pathway, decline of ATP and lipid peroxidation in rat cardiomyocytes...
September 2, 2016: Journal of Biochemical and Molecular Toxicology
Amina Ami, Habiba Oussedik-Oumehdi, Fatima Laraba-Djebari
A dermonecrotic metalloproteinase (CcD-II) was isolated from C. cerastes venom. Venom fractionation was performed using three chromatographic steps (molecular exclusion on Sephadex G-75, ion-exchange on DEAE-Sephadex A-50, and reversed-phase high-performance liquid chromatography on C8 column). CcD-II presented an apparent molecular mass of 39.9 kDa and displayed a dermonecrotic activity with a minimal necrotic dose of 0.2 mg/kg body weight. CcD-II showed proteolytic ability on casein chains and on α and β fibrinogen chains that was inhibited by ethylenediamine tetraacetic acid and 1,10-phenanthroline while remained unaffected by phenylmethylsulphonyl fluoride and heparin...
September 2, 2016: Journal of Biochemical and Molecular Toxicology
Mostafa A Darwish, Amira M Abo-Youssef, Marwa M Khalaf, Ali A Abo-Saif, Ibrahim G Saleh, Tamer M Abdelghany
Cisplatin (CP) is one of the most effective chemotherapeutic agents. Unfortunately, CP-induced nephrotoxicity hampered its use. This study aims to investigate the effect of vitamin E (Vit E) on CP-induced nephrotoxicity. Male white albino rats were divided to four group's six rats each and received either, 1% tween 80 in normal saline or Vit E (75 mg/kg) per day for 14 consecutive days or a single injection of CP (6 mg/kg) alone or CP (6 mg/kg) together with Vit E (75 mg/kg per day for 14 consecutive days)...
August 23, 2016: Journal of Biochemical and Molecular Toxicology
Mukesh Kumar, Eshvendar Reddy Kasala, Lakshmi Narendra Bodduluru, Vikas Kumar, Mangala Lahkar
Cardioprotection represents one of the most important and realistic aspects of preventive therapy today. Quercetin, a naturally occurring dietary flavone, has been studied extensively for its antioxidant properties. The objective of present study is to find out the cardioprotective activity and to explore the underlying mechanisms of quercetin pretreatment (50 mg/kg body weight, orally) for 14 days against isoproterenol (ISO; 100 mg/kg body weight, subcutaneously) induced myocardial infarction in Wistar rats...
August 15, 2016: Journal of Biochemical and Molecular Toxicology
Natalia Nuño-Lámbarri, Varenka J Barbero-Becerra, Misael Uribe, Norberto C Chávez-Tapia
Cholestasis results from defective bile flow through the biliary ducts leading to the accumulation of bile acids (BAs) in hepatocytes and serum. It has been seen that cholestasis is associated with hypercholesterolemia, which is a prerequisite for gallstone formation and primary biliary cirrhosis, being some of the most common gastrointestinal disorders in Western societies. Cytotoxic BAs induce proinflammatory mediators, oxidative stress, and apoptosis in hepatocytes, whereas cytoprotective BAs prevent them; they can also modify the plasmatic membrane structure of cells or mitochondrial outer membrane properties as well as the distribution of cholesterol, altering various proteins involved in BAs homeostasis...
August 12, 2016: Journal of Biochemical and Molecular Toxicology
Hong-Ling Yan, Li Li, Shu-Juan Li, Hai-Sheng Zhang, Wei Xu
The aim of this study is to determine the expression and roles of miR-346 in nasopharyngeal carcinoma (NPC). We showed that miR-346 was upregulated in NPC tissues compared with adjacent non-tumorous nasopharyngeal tissues. Inhibition of miR-346 significantly attenuated the migration and invasion of NPC cells. Luciferase reporter assay showed that miR-346 targeted the 3'-untranslated region (3'-UTR) of breast cancer metastasis suppressor 1 (BRMS1). Overexpression of miR-346 suppressed the endogenous expression of BRMS1 in NPC cells...
August 8, 2016: Journal of Biochemical and Molecular Toxicology
Randa M Breikaa, Hisham A Mosli, Ashraf B Abdel-Naim
Onabotulinumtoxin A (onabotA) is gaining wide medical use in children. The present study was planned to investigate the influence of its injection on the maturing testicular structures in rats. Immature rats were injected in the bilateral cremaster muscles by onabotA with three doses of (10, 20, and 40 U/kg) three times in a 2-week interval. The effect of these injections on fertility indices was examined. Levels of antisperm antibodies and several apoptosis parameters were also investigated. DNA content in form of ploidy and histopathological alterations were assessed...
August 5, 2016: Journal of Biochemical and Molecular Toxicology
Daniela Delwing-de Lima, Débora Delwing-Dal Magro, Cindy Laís Pett Vieira, Gislaine Maria Marestoni Grola, Débora Adriana Fischer, Angela Terezinha de Souza Wyse
We investigated the in vitro and in vivo effects of arginine (Arg) on thiobarbituric acid-reactive substances (TBA-RS) and on the activities of catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in renal tissues of rats. We also studied the influence of antioxidants (α-tocopherol plus ascorbic acid) and nitric oxide synthase inhibitor N(G) -nitro-l-arginine methyl ester (l-NAME) on the effects elicited by Arg. Results showed that Arg in vitro (1.5 mM) decreased SOD activity and increased the levels of TBA-RS in the renal medulla...
August 4, 2016: Journal of Biochemical and Molecular Toxicology
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