Nicorandil combats doxorubicin-induced nephrotoxicity via amendment of TLR4/P38 MAPK/NFκ-B signaling pathway.

Abstract:

:Nicorandil ameliorated doxorubicin-induced nephrotoxicity; this study aimed to show and explain the mechanism of this protection. A precise method was elucidated to study the effect of nicorandil on doxorubicin-induced nephrotoxicity in rats depending on the critical inflammation pathway TLR4/MAPK P38/NFκ-B. Adult male rats were subdivided into four groups. The 1st group was normal control, the 2nd group received nicorandil (3 mg/kg; p.o., for 4 weeks), the 3rd group received doxorubicin (2.6 mg/kg, i.p., twice per week for 4 weeks), and the fourth group was combination of doxorubicin and nicorandil for 4 weeks. Nephrotoxicity was assessed by biochemical tests through measuring Kidney function biomarkers such as [serum levels of urea, creatinine, albumin and total protein] besides renal kidney injury molecule-1 (KIM-1) and cystatin C], oxidative stress parameters such as [renal tissue malondialdehyde (MDA), reduced glutathione (GSH), SOD, catalase and nrf-2], mediators of inflammation such as [Toll like receptor 4 (TLR-4), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), p38 MAPK, Interleukin 1 beta (IL-1 β), and Tumor necrosis factor alpha (TNF-α)] and markers of apoptosis [BAX and Bcl-2 in renal tissue]. Finally, our data were supported by histopathology examination. Nicorandil pretreatment resulted in a significant decrease in nephrotoxicity biomarkers, oxidative stress markers, inflammatory mediators and prevented apoptosis through decreasing BAX and increasing Bcl-2 in renal tissues. Nicorandil prevented all the histological alterations caused by doxorubicin. Nicorandil is a promising antidote against doxorubicin-induced nephrotoxicity by neutralizing all toxicity mechanisms caused by doxorubicin through normalizing inflammatory cascade of TLR4/MAPK P38/NFκ-B.

journal_name

Chem Biol Interact

authors

Khames A,Khalaf MM,Gad AM,Abd El-Raouf OM,Kandeil MA

doi

10.1016/j.cbi.2019.108777

subject

Has Abstract

pub_date

2019-09-25 00:00:00

pages

108777

eissn

0009-2797

issn

1872-7786

pii

S0009-2797(19)30720-3

journal_volume

311

pub_type

杂志文章
  • The role of hydroxyl radicals in tetrachlorohydroquinone induced DNA strand break formation in PM2 DNA and human fibroblasts.

    abstract::Tetrachlorohydroquinone (TCHQ), which has previously been identified as a metabolite of pentachlorophenol, induces DNA strand breaks in isolated DNA and in human fibroblasts. Strand break formation in PM2 DNA is prevented by the addition of catalase and the hydroxyl radical scavengers DMSO, ethanol and mannitol, where...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/0009-2797(90)90047-q

    authors: Carstens CP,Blum JK,Witte I

    更新日期:1990-01-01 00:00:00

  • Subunit communication in tetrameric class 2 human liver aldehyde dehydrogenase as the basis for half-of-the-site reactivity and the dominance of the oriental subunit in a heterotetramer.

    abstract::Data has been published showing that in heterotetrameric liver mitochondrial aldehyde dehydrogenase composed of the active (E487) and the inactive Oriental-variant (K487) subunit, the Oriental variant was dominant and caused the inactivation of the E487 subunit. The published structures of the enzyme showed that the g...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/s0009-2797(00)00221-0

    authors: Weiner H,Wei B,Zhou J

    更新日期:2001-01-30 00:00:00

  • The profile of urinary metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats is determined by its pulmonary metabolism.

    abstract::Metabolism of the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in rats was compared to metabolism in primary lung and liver cells. Untreated rats and rats pretreated with phenobarbital, acetone or phenethyl isothiocyanate (PEITC) were used for all experiments. Also the influence of...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/s0009-2797(99)00083-6

    authors: Schneider T,Frei E,Wiessler M

    更新日期:1999-04-15 00:00:00

  • Potentiation of dimethylnitrosamine genotoxicity in rat hepatocytes isolated following ethanol treatment in vivo.

    abstract::Unscheduled DNA synthesis (UDS), following exposure to dimethylnitrosamine (DMN), was potentiated in cultured hepatocytes isolated following treatment of rats for 14 or 28 days with 20% ethanol/5% sucrose solution. Ethanol treatment was associated with increased UDS, a concomitant increase in hepatic microsomal protei...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/0009-2797(84)90039-5

    authors: Olson MJ,Pounds JG,Casciano DA

    更新日期:1984-08-01 00:00:00

  • The bioactivation of 1,2-dibromoethane in rat hepatocytes: deuterium isotope effect.

    abstract::The metabolism and genotoxicity of 1,2-dibromoethane (EDB) and its deuterium substituted analog ( d4EDB ) were studied in isolated rat hepatocytes. There was a marked isotope effect on the metabolism of EDB by hepatocytes. This was due to decreased microsomal oxidation of d4EDB . Cytosolic metabolism of EDB, as measur...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/0009-2797(84)90063-2

    authors: White RD,Petry TW,Sipes IG

    更新日期:1984-04-01 00:00:00

  • RNA interference against stromal interacting molecule-1 (STIM1) ameliorates ethanol-induced hepatotoxicity.

    abstract::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 i...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2018.04.025

    authors: Cui R,Li R,Guo X,Jia X,Yan M

    更新日期:2018-06-01 00:00:00

  • Effect of tetrahydrocurcumin on the profiles of drug-metabolizing enzymes induced by a high fat and high fructose diet in mice.

    abstract::Cytochrome P450 (CYP), a superfamily of hepatic monooxygenase enzymes, catalyzes biotransformation of endogenous compounds and xenobiotics. Modification of CYPs associated with metabolic diseases and continuous consumption of diet with excessive energy levels. Tetrahydrocurcumin (THC) exhibited beneficial effects in m...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2015.06.022

    authors: Jearapong N,Chatuphonprasert W,Jarukamjorn K

    更新日期:2015-09-05 00:00:00

  • Overexpression of microRNA-519d-3p suppressed the growth of pancreatic cancer cells by inhibiting ribosomal protein S15A-mediated Wnt/β-catenin signaling.

    abstract::Ribosomal protein S15A (RPS15A) has emerged as a novel oncogene of various human cancers. However, whether RPS15A is involved in pancreatic cancer remains unclear. In this study, we aimed to investigate the potential relevance of RPS15A in pancreatic cancer and elucidate the underlying regulatory mechanism. We found t...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2019.02.026

    authors: Liang J,Liu Y,Zhang L,Tan J,Li E,Li F

    更新日期:2019-05-01 00:00:00

  • Effect of sydnone SYD-1, a mesoionic compound, on energy-linked functions of rat liver mitochondria.

    abstract::An important antitumour effect of SYD-1 (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate) has been shown. We now report the effects of this mesoionic compound on mitochondrial metabolism. SYD-1 (1.5 micromol mg(-1) protein) dose-dependently inhibited the respiratory rate by 65% and 40% in state 3 using sodium gl...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2007.06.003

    authors: Halila GC,de Oliveira MB,Echevarria A,Belém AC,Rocha ME,Carnieri EG,Martinez GR,Noleto GR,Cadena SM

    更新日期:2007-09-20 00:00:00

  • An evolutionary perspective on the first disulfide bond in members of the cholinesterase-carboxylesterase (COesterase) family: Possible outcomes for cholinesterase expression in prokaryotes.

    abstract::Within the alpha/beta hydrolase fold superfamily of proteins, the COesterase group (carboxylesterase type B, block C, cholinesterases …) diverged from the other groups through simultaneous integration of an N-terminal, first disulfide bond and a significant increase in the protein mean size. This first disulfide bond ...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2019.05.016

    authors: Chatonnet A,Brazzolotto X,Hotelier T,Lenfant N,Marchot P,Bourne Y

    更新日期:2019-08-01 00:00:00

  • A review of the epidemiology of 1,3-butadiene and chloroprene.

    abstract::Butadiene epidemiologic research has focused primarily on one cohort of workers in the North American styrene-butadiene rubber (SBR) industry and on the largest cohort of workers in the United States butadiene monomer industry. The most recent studies of these populations are characterized by carefully enumerated stud...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章,评审

    doi:10.1016/s0009-2797(01)00169-7

    authors: Acquavella JF,Leonard RC

    更新日期:2001-06-01 00:00:00

  • Immunological properties of low molecular-weight proteins binding heavy metals in rat kidney and liver.

    abstract::Two homogenous fractions of hepatic metallothioneins ((Cd,Zn) MT-1 and (Cd,Zn) MT-2) and renal metal binding proteins ((Bi,Cu) BP-1 and (Bi,Cu) BP-2) were isolated from rats exposed to heavy metals and specific antisera to them were produced in rabbits. These antisera were tested by immunodiffusion and immunoelectroph...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/0009-2797(80)90048-4

    authors: Zelazowski AJ,Szymańska JA,Cierniewski CS

    更新日期:1980-12-01 00:00:00

  • Glucocorticoids differentially control synthesis of acetylcholinesterase and butyrylcholinesterase in rat liver and brain.

    abstract::Mammalian organisms possess two cholinesterases: acetylcholinesterase (AChE, EC 3.1.1.7.) and butyrylcholinesterase (BuChE, EC 3.1.1.8.). A clear explanation for this dual expression of acetylcholine-hydrolyzing enzymes is still missing. Better knowledge on how these two enzymes respond to various physiological or pha...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/s0009-2797(99)00045-9

    authors: Weber U,Brank M,Grubic Z

    更新日期:1999-05-14 00:00:00

  • The impact of skin decontamination on the time window for effective treatment of percutaneous VX exposure.

    abstract::The main goal of the present study was to obtain insight into depot formation and penetration following percutaneous VX poisoning, in order to identify an appropriate decontamination window that can enhance or support medical countermeasures. The study was executed in two phases, using the hairless guinea pig as an an...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2016.02.001

    authors: Joosen MJ,van den Berg RM,de Jong AL,van der Schans MJ,Noort D,Langenberg JP

    更新日期:2017-04-01 00:00:00

  • The mutagenicity of chloroethylene oxide, chloroacetaldehyde, 2-chloroethanol and chloroacetic acid, conceivable metabolites of vinyl chloride.

    abstract::Previous investigations have shown that the carcinogen vinyl chloride causes base-pair substitution in the bacterium Salmonella typhimurium. The ability of four conceivable metabolites-chloroethylene oxide, chloroacetaldehyde, 2-chloroethanol and chloroacetic acid-to cause base-pair substitution directly in Salmonella...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/0009-2797(76)90041-7

    authors: Rannug U,Göthe R,Wachtmeister CA

    更新日期:1976-03-01 00:00:00

  • Sodium acetate protects against nicotine-induced excess hepatic lipid in male rats by suppressing xanthine oxidase activity.

    abstract::Fatty liver is the hepatic consequence of chronic insulin resistance (IR) and related syndromes. It is mostly accompanied by inflammatory and oxidative molecules. Increased activity of xanthine oxidase (XO) exerts both inflammatory and oxidative effects and has been implicated in metabolic derangements including non-a...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2019.108929

    authors: Dangana EO,Omolekulo TE,Areola ED,Olaniyi KS,Soladoye AO,Olatunji LA

    更新日期:2020-01-25 00:00:00

  • Functional analysis of a novel repressor LuxR in Comamonas testosteroni.

    abstract::Comamonas testosteroni (C. testosteroni) ATCC11996 is a gram negative bacterium which can use steroid as a carbon and energy source. 3,17β-hydroxysteroid dehydrogenase (3,17β-HSD) is a key enzyme for the degradation of steroid hormones in C. testosteroni. The LuxR regulation family is a group of regulatory proteins wh...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2017.03.002

    authors: Ji Y,Pan T,Zhang Y,Xiong G,Yu Y

    更新日期:2017-10-01 00:00:00

  • Prevention of prostate cancer through custom tailoring of chemopreventive regimen.

    abstract::One practical way to control cancer is through chemoprevention, which refers to the administration of synthetic or naturally occurring agents to block, reverse or delay the process of carcinogenesis. For a variety of reasons, the most important of which is human acceptance, for chemopreventive intervention naturally o...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章,评审

    doi:10.1016/j.cbi.2007.03.001

    authors: Siddiqui IA,Afaq F,Adhami VM,Mukhtar H

    更新日期:2008-01-30 00:00:00

  • Expression of AKR1B1, AKR1C3 and other genes of prostaglandin F2α biosynthesis and action in ovarian endometriosis tissue and in model cell lines.

    abstract::Endometriosis is a frequent benign gynecological disease characterized by endometrial tissue outside the uterine cavity. The estimated prevalence in the general population is 6-10%, but this reaches 30-50% in women with infertility and/or pain. As ectopic tissue within the pelvic cavity provokes inflammation, endometr...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2014.11.009

    authors: Sinreih M,Anko M,Kene NH,Kocbek V,Rižner TL

    更新日期:2015-06-05 00:00:00

  • Influence of pH on the reactivity of diphenyl ditelluride with thiols and anti-oxidant potential in rat brain.

    abstract::Thiol oxidation by diphenyl ditelluride is a favorable reaction and may be responsible for alteration in regulatory or signaling pathways. We have measured rate constants for reactions of diphenyl ditelluride with cysteine, dimercaptosuccinic acid, glutathione and dithiothreitol in phosphate buffer. The relative react...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2008.12.013

    authors: Hassan W,Ibrahim M,Nogueira CW,Braga AL,Deobald AM,Mohammadzai IU,Rocha JB

    更新日期:2009-06-15 00:00:00

  • Trialkyl phosphorothioates and glutathione S-transferases.

    abstract::Using a rat liver cytosol source of enzyme trialkyl phosphorothioates have been shown to be substrates of glutathione S-transferases. Using OSS-trimethyl phosphorodithioate (OSS-Me(O] and OOS-trimethyl phosphorothioate (OOS-Me(O] the methyl transferred to the sulphydryl of glutathione is that attached to phosphorus vi...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/s0009-2797(85)80166-6

    authors: Aldridge WN,Grasdalen H,Aarstad K,Street BW,Norkov T

    更新日期:1985-07-01 00:00:00

  • Urban air and tobacco smoke in benzene exposure in a cohort of traffic policemen.

    abstract::Benzene (B) is a typical micro-pollutant present in air, especially urban air. In this study a possible correlation between personal benzene exposure and S-phenylmercapturic acid (S-PMA) as a biomarker of internal dose was evaluated in a cohort of traffic policemen. The results confirm that S-PMA is significantly corr...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2005.03.028

    authors: Bono R,Traversi D,Maestri L,Schilirò T,Ghittori S,Baiocchi C,Gilli G

    更新日期:2005-05-30 00:00:00

  • Bioinorganic and bioorganic studies of liver alcohol dehydrogenase.

    abstract::Liver alcohol dehydrogenase (E.C.1.1.1.1) is an NAD(+)/NADH dependent enzyme with a broad substrate specificity being active on an assortment of primary and secondary alcohols. It catalyzes the reversible oxidation of a wide variety of alcohols to the corresponding aldehydes and ketones as well as the oxidation of cer...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/s0009-2797(00)00263-5

    authors: Pocker Y

    更新日期:2001-01-30 00:00:00

  • In vitro skin decontamination of the organophosphorus pesticide Paraoxon with nanometric cerium oxide CeO2.

    abstract::Organophosphorus compounds (OP), which mainly penetrate via the percutaneous pathway, represent a threat for both military and civilians. Body surface decontamination is vital to prevent victims poisoning. The development of a cost-effective formulation, which could be efficient and easy to handle in case of mass cont...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2016.04.035

    authors: Salerno A,Devers T,Bolzinger MA,Pelletier J,Josse D,Briançon S

    更新日期:2017-04-01 00:00:00

  • The in vitro interaction with DNA of several hypoxic radiosensitizers.

    abstract::The five 5-nitroimidazole derivatives and the four glyoxylic compounds tested in this paper for their interaction with DNA with and without irradiation had previously been reported to act as radiosensitizers at a cellular level. Our aim was to find if the radiosensitizing activity of these products could be due to the...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/0009-2797(89)90038-0

    authors: Santos Peinado L,Cornago Ramirez P,Lopez Zumel C

    更新日期:1989-01-01 00:00:00

  • In vitro and in vivo anticancer activity of posterior salivary gland toxin from the cuttlefish Sepia pharaonis, Ehrenberg (1831).

    abstract::Posterior salivary gland (PSG) toxins are high molecular weight toxins secreted by cephalopods and gastropods which possess immense potentials in biomedical applications. In the present study, the biomedical potentials of the PSG toxin from the cuttlefish, S. pharaonis was determined in vitro and in vivo. The cytostat...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/j.cbi.2017.04.002

    authors: Karthik R,Manigandan V,Ebenezar KK,Vijayashree R,Saravanan R

    更新日期:2017-06-25 00:00:00

  • Effects of arenastatin A and its synthetic analogs on microtubule assembly.

    abstract::Inhibition of microtubule assembly by arenastatin A (1) and five synthetic analogs (3-7) was examined. Arenastatin A and the triamide 6 showed potent and moderately strong inhibitory activities, respectively (IC50; 2.3 microM for 1, 7.8 microM for 6) and also depolymerized preformed microtubules. The other analogs tes...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/s0009-2797(96)03743-x

    authors: Koiso Y,Morita K,Kobayashi M,Wang W,Ohyabu N,Iwasaki S

    更新日期:1996-12-20 00:00:00

  • DNA-protein cross-linking by chromium salts.

    abstract::DNA-protein cross-links were detected in several types of mammalian cells in culture when they were exposed to chromate salts. The cell types included human bronchial epithelial cells--the apparent cell type of origin of the malignancies reported in chromate workers. The level of cross-linking was proportional to the ...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/0009-2797(81)90077-6

    authors: Fornace AJ Jr,Seres DS,Lechner JF,Harris CC

    更新日期:1981-09-01 00:00:00

  • Polymorphisms in the human AH receptor.

    abstract::The AH receptor (AHR) mediates toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as well as induction of three cytochrome P450 enzymes and certain Phase II enzymes. In laboratory animals, genetic variations in the AHR lead to substantial differences in sensitivity to biochemical and toxic effects of TCDD and rela...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章,评审

    doi:10.1016/s0009-2797(02)00071-6

    authors: Harper PA,Wong Jm,Lam MS,Okey AB

    更新日期:2002-09-20 00:00:00

  • Biologically active aromatic retinoids bearing azido photoaffinity-labeling groups and their binding to cellular retinoic acid-binding protein.

    abstract::Retinoids bearing azido photoaffinity-labeling groups (azidoretinoids) have potential as probes for investigating the molecular mechanisms of action of all-trans-retinoic acid (RA) as mediated by its cellular retinoic acid-binding protein (CRABP) and nuclear receptor proteins. Two new azidoretinoids, 3-azido-4-[2-(5,6...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章

    doi:10.1016/0009-2797(90)90072-u

    authors: Sani BP,Wille JJ Jr,Dawson MI,Hobbs PD,Bupp J,Rhee S,Chao WR,Dorsky A,Morimoto H

    更新日期:1990-01-01 00:00:00