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Chemico-biological Interactions

Thomas J Flynn, Sanah N Vohra
Caco-2 cells are a commonly used model for estimating the intestinal bioavailability of single chemical entity pharmaceuticals. Caco-2 cells, when induced with calcitriol, also express other biological functions such as phase I (CYP) and phase II (glucuronosyltransferases) drug metabolizing enzymes which are relevant to drug-supplement interactions. Intestinal bioavailability is an important factor in the overall safety assessment of products consumed orally. Foods, including herbal dietary supplements, are complex substances with multiple chemical components...
May 18, 2018: Chemico-biological Interactions
Yifei Wang, Shengli Wang, Jianhua Liu, Yanxiao Lu, Donghui Li
Osteosarcoma (OS) is the most common bone malignancy in children and adolescents. Combined treatments of anti-cancer drugs can remarkably improve chemotherapeutic outcomes. Gemcitabine and licoricidin both have potential anti-tumor activity in several cancers. However, the combined therapeutic efficiency of gemcitabine and licoricidin for OS has not been explored. Here, we found that licoricidin or gemcitabine inhibited OS cell viability in a dose-dependent manner. Cotreatment with licoricidin and gemcitabine enhanced gemcitabine-induced cytotoxicity in OS cells...
May 18, 2018: Chemico-biological Interactions
Subhadip Hajra, Arup Ranjan Patra, Abhishek Basu, Prosenjit Saha, Sudin Bhattacharya
Various epidemiological and preclinical studies have already established the cancer chemopreventive potential of naturally occurring glucosinolate breakdown product Indole-3-Carbinol (I3C) as well as its abilities to induce selective cell death towards malignant cell. Therefore, the objective of the present study is to improve the therapeutic efficacy and prevention of doxorubicin (DOX)-induced toxicity, by the concurrent use of Indole-3-Carbinol (I3C). In this study, I3C was administered (20 mg/kg b.w., p...
May 15, 2018: Chemico-biological Interactions
Chun-Ping Lu, Chien-Yu Huang, Szu-Hsuan Wang, Chih-Hsien Chiu, Lan-Hui Li, Kuo-Feng Hua, Tzu-Hua Wu
Macrophages and inflammasome pathway are involved in high-glucose toxicity and development of insulin resistance. Silymarin (SMR) was known to modulate glucose homeostasis and reduce inflammation. However, it is still unknown whether SMR possess anti-hyperglycemic effects in diabetic-like knockout mice (Hnf-1αkin/- /Ins.cre mice) with insulin resistance and also unclear how SMR regulates LPS induced stress markers and pro-inflammatory cytokines under stresses of high glucose (HG) or NLRP3 inflammasome activation...
May 10, 2018: Chemico-biological Interactions
Andrey A Toropov, Alla P Toropova, Emilio Benfenati, Jean Lou Dorne
The CORAL software has been applied to the development of classification models for pesticides relative to two pharmacokinetic properties in humans: (i) gastro-intestinal absorption; and (ii) blood-brain barrier permeation. These models were built up using categorical data on pesticide absorption and brain permeation split into training, invisible training, calibration and external validation sets using Monte Carlo simulations. The models were assessed using several random splits into the training and validation sets...
May 10, 2018: Chemico-biological Interactions
Nita Vasaikar, Umesh Mahajan, Kalpesh R Patil, Kapil Suchal, Chandragouda R Patil, Shreesh Ojha, Sameer N Goyal
Cisplatin has been widely used as a first-line agent against various forms of solid cancers. However, nephrotoxicity is the major limiting factor for its clinical use. Several clinical and pre-clinical studies have suggested different strategies for the reduction of cisplatin-induced nephrotoxicity. The present study was conducted to investigate the efficacy of D-Pinitol, against cisplatin-induced nephrotoxicity in Swiss albino mice. A single intraperitoneal injection of cisplatin (20 mg/kg) was used to induce nephrotoxicity in mice...
May 9, 2018: Chemico-biological Interactions
Ramiya Kumar, Elizabeth J Litoff, W Tyler Boswell, William S Baldwin
Recent studies indicate a role for the constitutive androstane receptor (CAR), pregnane X-receptor (PXR), and hepatic xenobiotic detoxifying CYPs in fatty liver disease or obesity. Therefore, we examined whether Cyp3a-null mice show increased obesity and fatty liver disease following 8-weeks of exposure to a 60% high-fat diet (HFD). Surprisingly, HFD-fed Cyp3a-null females fed a HFD gained 50% less weight than wild-type (WT; B6) females fed a HFD. In contrast, Cyp3a-null males gained more weight than WT males, primarily during the first few weeks of HFD-treatment...
May 5, 2018: Chemico-biological Interactions
A Ramadan, Nehal Afifi, Nemat Z Yassin, Rehab F Abdel-Rahman, Sahar S Abd El-Rahman, Hany M Fayed
Liver fibrosis is a major health issue leading to high morbidity and mortality. The potential anti-fibrotic activity and the effect of mesalazine on osteopontin (OPN), an extra cellular matrix (ECM) component were evaluated in TAA-induced liver fibrosis in rats. For this purpose, forty-two adult male Wistar rats were divided into six groups. All animals, except the normal control, were intraperitoneally injected with TAA (200 mg/kg) twice per week for 6 weeks. In the hepato-protective study, animals were administered mesalazine (50 and 100 mg/kg, orally) for 4 weeks before induction of liver fibrosis then concomitantly with TAA injection...
May 5, 2018: Chemico-biological Interactions
Yejin Lee, Hyoung-Goo Park, Vitchan Kim, Myung-A Cho, Harim Kim, Thien-Hoang Ho, Kyoung Sang Cho, Im-Soon Lee, Donghak Kim
Human cytochrome P450 2B6 is an important hepatic enzyme for the metabolism of xenobiotics and clinical drugs. Recently, more attention has been paid to P450 2B6 because of the increasing number of drugs it metabolizes. It has been known to interact with terpenes, the major constituents of the essential oils used for various medicinal purposes. In this study, the effect of monoterpenes on P450 2B6 catalytic activity was investigated. Recombinant P450 2B6 was expressed in Escherichia coli and purified using Ni-affinity chromatography...
April 30, 2018: Chemico-biological Interactions
Emílio V Lage, Joana Magalhães, Marina Pinheiro, Salette Reis
In this work, we studied the effects of the N-alkyl group (methyl, cyclopentyl) in the piperazine ring of, respectively, rifampicin (RIF) and rifapentine (RPT) to correlate this substitution with their differential pharmacokinetic properties and overall clinical performance. Since this group is their only structural change, and given that they share the same pharmacological target, differences in their therapeutic behavior may respond to this asset, particularly in their interaction with lipid membranes across the organism...
April 27, 2018: Chemico-biological Interactions
Na Liu, Yan-Hua Qi, Chuan-Tao Cheng, Wen Bin Yang, Anshoo Malhotra, Qi Zhou
RNA interference is a highly specific as well as efficient technology for gene therapy application in molecular oncology. The present study was planned to develop an efficient and stable tumor selective delivery mechanism for siRNA gene therapy for the purpose of both diagnosis as well as therapy. We have used 20 Male wistar rats for the formation of colon cancer model and utilized albumin as carrier molecule for the delivery of siRNA against vascular endothelial growth factor receptor 2 (VEGF R2). The study results confirmed efficient delivery of siRNA at tumor site as confirmed by tagging of siRNA-albumin complex with 99m TC...
April 27, 2018: Chemico-biological Interactions
Cheng Teng Ng, Wai Cheong George Yip, Ee Sin Chen, Wan Yan Rebecca Poh, Boon Huat Bay, Lin Yue Lanry Yung
Gold nanoparticles (AuNPs) have emerging applications in biomedicine and the industry. Exposure to AuNPs has previously been shown to alter the transcriptional activity of nuclear factor kappa B (NF-kB), which is known to mediate physiological and pathological processes. This study seeks to provide mechanistic insights into AuNP-induced NF-kB activation in Small Airway Epithelial Cells (SAECs) in vitro. Increased NF-kB transcriptional activity (quantified by the luciferase reporter assay) was observed in AuNP-treated SAECs...
April 26, 2018: Chemico-biological Interactions
Ya-Li Zhang, Shu-Kai Qiao, Rong-Ying Wang, Xiao-Nan Guo
Ischemia/reperfusion (I/R) injury is a main cause of acute kidney injury (AKI), and currently lacks effective therapies. This study is to investigate the level of Neutrophil gelatinase-associated lipocalin (NGAL) and autophagy status during renal I/R injury, so as to determine whether the exogenous NGAL protein could exert a protective effect for I/R injury and explore the potential mechanisms. Forty male Wistar rats were randomly divided into the following four groups: Sham, I/R, pre-treated with NGAL before I/R (I/R + pre-N), treated with NGAL after I/R (I/R + post-N)...
April 25, 2018: Chemico-biological Interactions
Ruibing Cui, Rong Li, Xiaolan Guo, Xiaoqing Jia, Ming Yan
Previously we have demonstrated that stromal interacting molecule-1 (STIM1) was involved in ethanol induced liver injury. However, the exact pathogenic mechanism of STIM1 in alcoholic liver disease (ALD) is still unknown. We constructed plasmid vectors encoding short-hairpin RNA against STIM1 to investigate its role in ALD in the rat liver cell line BRL and in Sprague-Dawley rats. The results showed that STIM1 targeted sh-RNA (Sh-STIM1) significantly ameliorated ethanol-induced BRL cells injury and liver injury in rats with 20 weeks-induced alcoholic liver disease...
April 25, 2018: Chemico-biological Interactions
Chinedum Eleazu, Ayogu Charles, Kate Eleazu, Ngozi Achi
The incidence of type 2 diabetes mellitus (T2DM) has been on the increase in recent times. Although several oral treatments for T2DM are available, some of them have been found to elicit undesirable side effects. This therefore underscores the need for new treatment options with lesser side effects than the existing ones for people with T2DM. Free fatty acid receptor 1 (FFAR1), also known as GPR40, belongs to a class of G-protein coupled receptors that are encoded by FFAR1 genes in humans. It is expressed in the pancreatic β-cells and it is activated by medium- and long-chain saturated and unsaturated fatty acids...
April 25, 2018: Chemico-biological Interactions
Ju-Hee Lee, Su Youn Baek, Eun Jeong Jang, Sae Kwang Ku, Kyu Min Kim, Sung Hwan Ki, Chang-Eop Kim, Kwang Il Park, Sang Chan Kim, Young Woo Kim
Oxyresveratrol (OXY) is a naturally occurring polyhydroxylated stilbene that is abundant in mulberry wood (Morus alba L.), which has frequently been supplied as a herbal medicine. It has been shown that OXY has regulatory effects on inflammation and oxidative stress, and may have potential in preventing or curing nonalcoholic fatty liver disease (NAFLD). This study examined the effects of OXY on in vitro model of NAFLD in hepatocyte by the liver X receptor α (LXRα)-mediated induction of lipogenic genes and in vivo model in mice along with its molecular mechanism...
April 24, 2018: Chemico-biological Interactions
Yunjiang Yu, Ruixue Ma, Lin Yu, Ze Cai, Hongyan Li, You Zuo, Zhengdong Wang, Hui Li
Tetrabromobisphenol A (TBBPA) is one of the world's most widely used brominated flame retardants (BFRs) and considered as persistent halogenated contaminant. E-wastes contain a range of toxic chemicals, including BFRs and heavy metals, exerting adverse impacts to human health and environment. Nevertheless, comprehensive evaluation on combined toxicity of these co-existing pollutants is limited. This study conducted a subchronic effects of cadmium and TBBPA on the development and antioxidative defense system as well as thyroid functions in female rats through single and combined exposure at environmentally relevant doses for a 20-day consecutive administration...
April 24, 2018: Chemico-biological Interactions
Guo-Dong Yao, Qian Sun, Xiao-Yu Song, Xiao-Xiao Huang, Shao-Jiang Song
Hepatocellular carcinoma (HCC) is a primary malignant tumor with very poor prognosis. To search for more effective compounds for HCC treatment, two new pairs of flavan enantiomers, daphnegiranol C1 /C2 (1a/1b) and daphnegiranol D1 /D2 (2a/2b), were isolated from the stem bark and roots of Daphne giraldii by using chiral chromatography. MTT assay was applied to evaluate their cytotoxicity against three hepatocarcinoma cell lines (Hep3B, MHCC97H, HepG2) as well as a normal liver cell line L02. The results showed that these compounds preferred to inhibit the growth of Hep3B cells (p53 null)...
April 24, 2018: Chemico-biological Interactions
Ying Sun, Xin Xin, Kehan Zhang, Tiantian Cui, Ying Peng, Jiang Zheng
Chrysophanol, a major anthraquinone component occurring in many traditional Chinese herbs, is accepted as important active component with various pharmacological actions such as antibacterial and anticancer activity. Previous studies demonstrated that exposure to chrysophanol induced cytotoxicity, but the mechanisms of the toxic effects remain unknown. In the present metabolism study, three oxidative metabolites (M1-M3, aloe-emodine, 7-hydroxychrysophanol, and 2-hydroxychrysophanol) and five GSH conjugates (M4-M8) were detected in rat and human liver microsomal incubations of chrysophanol supplemented with GSH, and the formation of the metabolites was NADPH dependent except M4 and M5...
April 23, 2018: Chemico-biological Interactions
Mei-Juan Xu, Li-Feng Jiang, Ting Wu, Ji-Hong Chu, Yi-Dan Wei, Ji-Ye Aa, Guang-Ji Wang, Hai-Ping Hao, Wen-Zheng Ju, Ping Li
The use of Chinese herbal medicines and natural products has become increasingly popular in both China and Western societies as an alternative medicine for the treatment of diseases or as a health supplement. Danshen, the dried root of Salvia miltiorrhiza (Fam.Labiatae), which is rich in phenolic acids and tanshinones, is a widely used herbal medicine for the treatment of cardio-cerebrovascular diseases. The goal of this study was to examine the inhibitory effects of fifteen components derived from Danshen on CYP2C8 and CYP2J2, which are expressed both in human liver and cardiovascular systems...
April 21, 2018: Chemico-biological Interactions
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