N-acetylcysteine attenuated sepsis-induced cardiac depression: down-regulation of MMP-2 pathway in mice

crossMark

pcij picture in post

 
Nasser Ghaly Yousif¹*, Bassim I. Mohammad², Najah Hadi³, Musaed H. Al-Dahhan¹, Safa Al-khalidy¹

Author Affiliations *Corresponding Author: Electronic address: yousif_ghaly@yahoo.com. ¹Muthanna University School of Medicine. ²Qadyssia University. ³Department of Pharmacology, University of Kufa

Abstract

During sepsis, the inflammatory responses mediate myocardium injury, including LV dysfunction and cardiac pathophysiological changes. To understanding the pathway of sepsis in cardiac depression, we tested the hypothesis that N-acetylcysteine attenuated sepsis-induced cardiac depression through down-regulation of MMP-2 pathway. Adult (4 to 6 months) male Albino-Webster mice, and their weights ranged from 25 to 30 gm, were pre-treated with N-acetylcysteine ip following cecal ligation and puncture (CLP). Left ventricle (LV) function was assessed using a micro-catheter system. MCP-1 and cytokines mediator’s in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay (ELISA). Further, the cardiac MMP2 measured by qRT-PCR and the pathological changes and cells injuries in the myocardium were examined using hematoxylin and eosin staining. CLP mice displayed worse LV function. The exaggerated cardiac depression in CLP mice was associated with higher levels of MCP-1 and cytokines in plasma and myocardium together with greater cardiac levels of cTn-I and MMP2. Neutralization of sepsis by NAC resulted in improved LV function and greater reductions in inflammatory mediators, MMP2 and myocardium injury. Taken together, NAC improved LV function following sepsis through down-regulation of MMP2 and serve as a potential therapeutic in cardiac endotoxemia.

Keywords: N-acetylcysteine; Myocardium injury; Sepsis

Article citationReferencesFull-Text/PDFFeedback The citation data is computed by the crossref service:

citedby

References

  1. Kumar A, Haery C, Parrillo JE. Myocardial dysfunction in septic shock. Crit Care Clin 2002;16:251-287. [PubMed]
  2. Durum R, Memon JF, Mackall TN, et al. Critical role of farnesyltransferase inhibitor in protective myocardial function after endotoxemia in rat model. American Journal of BioMedicine 2014;2(7):827-839. [Abstract/Full-Text]
  3. Caroline M, Michelsen T, Lorenz DM, Dorfmüller KA. Cytoplasmic double-stranded DNA trigger NALP3 after global myocardial I/R: crosstalk AIM2/inflammasome. Pathophysiology of cell injury journal 2015;4(1):1-12. [Abstract/Full-Text]
  4. Slimani H, Zhai Y, Yousif NG, Ao L, Zeng Q, Fullerton D Meng X. Enhanced monocyte chemoattractant protein-1 production in aging mice exaggerates cardiac depression during endotoxemia. Crit Care 2014;18(5):527. [PubMed]
  5. Meng X, Brown JM, Ao L, et al. Myocardial gene reprogramming associated with a cardiac cross-resistant state induced by LPS preconditioning. Am J Physiol 1998;275:C475-C483. [Abstract/Full-Text]
  6. Hullmann G, Azfer A, Hensley J, Bergese A, Lefer J. Role of IL-1B in TLR4-mediated MCP-1expression: renal sepsis. American Journal of BioMedicine 2015;3(1):22-31. [Abstract/Full-Text]
  7. Al-Amran FG, Yousif NG, Meng X. A TLR4-MCP-1-macrophage IL-18 cascade plays a major role in myocardial injury and cardiac dysfunction after permanent ischemia. Journal of Surgical Research 2011;165(2):265-266. [Abstract]
  8. Bravo A, Kumm K, Lamy C, Jeanneau J, Cuello G, Lefer J. H2 therapy protects myocardial cell injury induce by sepsis via attenuated expression the level of HMGB1. Pathophysiology of cell injury journal 2012;1(1):10-19. [Abstract/Full-Text]
  9. Yousif NG, Al-Amran F. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin) induced cardiac injury in mice. BMC Cardiovasc Disord 2011;11:62. [PubMed]
  10. Goodman J, Putensen A, Calandra R, Dios J, Bacher G, Tracey C. Critical role of macrophage migration inhibitory factor in sepsis via interfere with MCP-1/CCL2 signaling pathway. American Journal of BioMedicine 2014;2(6):688-701. [Abstract/Full-Text]
  11. Kumar A, Thota V, Dee L, Olson J, Uretz E, Parrillo J. Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum. J Exp Med 1996;183:949-958. [PubMed]
  12. Weisensee D, Bereiter-Hahn J, Schoeppe W, Low-Friedrich I. Effects of cytokines on the contractility of cultured cardiac myocytes. Int J Immunopharmacol 1993;15:581-587. [PubMed]
  13. Turler A, Schwarz NT, Turler E, Kalff JC, Bauer AJ. MCP-1 causes leukocyte recruitment and subsequently endotoxemic ileus in rat. Am J Physiol Gastrointest Liver Physiol 2002;282:G145-G155. [PubMed]
  14. Austin E, Yousif NG, Ao L, Cleveland JC, Fullerton D, Meng X. Ghrelin reduces myocardial injury following global ischemia and reperfusion via suppression of myocardial inflammatory response. American journal of BioMedicine 2013;1(2):38-48.  [Abstract/Full-Text
  15. Deshmane L, Kremlev S, Amini S, Sawaya E. Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res 2009;29:313-326. [PubMed]
  16. Chagnon F, Metz CN, Bucala R, Lesur O. Endotoxin-induced myocardial dysfunction: effects of macrophage migration inhibitory factor neutralization. Circ Res 2005;96:1095-1102. [PubMed]
  17. Kobayashi Y. The role of chemokines in neutrophil biology. Front Biosci 2008;13:2400-2407. [PubMed]
  18. Rink L, Hebel T, Fukumot J. Sepsis and signal transduction pathway: cross-talk TLR4/ MyD88/TRIF. American Journal of BioMedicine 2015;3(4):150-163. [Abstract/Full-Text]
  19. Panas D, Khadour FH, Szabo C, Schulz R. Proinflammatory cytokines depress ardiac efficiency by a nitric oxide-dependent mechanism. Am J Physiol 1998;275(3Pt 2):H1016-H1023. [PubMed]
  20. Xie W, Wolin MS. Role of nitric oxide and its interaction with superoxide in the suppression of cardiac muscle mitochondrial respiration. Involvement in response to hypoxia/reoxygenation. Circulation 1996;94:2580-2586. [Abstract/Full-Text]
  21. Zingarelli B, Salzman AL, Szabo C. Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circ Res 1998;83:85-94. [Abstract/Full-Text]
  22. Ohlsson K, Bjork P, Bergenfeldt M, Hageman R, Thompson RC. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature 1990;348:550-552. [PubMed]
  23. Ogiku L, Fujii R, Xiao S, Xuehao L. Meloxicam attenuates brain cell injury following cerebral ischemia and reperfusion via down regulation of proinflammatory response. Pathophysiology of cell injury journal 2013;2(1):1-11. [PubMed]
  24. Yousif NG. Novel therapeutic role of siglec-E in down-regulation TLR4-mediated inflammatory response after global myocardial ischemia and reperfusion. Cardiovascular research 2014;103:s90. [Abstract]
  25. Grupper R, Edward R, Walter C, Varnous E. Critical role of microRNAs after global myocardial ischemia and reperfusuion. American Journal of BioMedicine 2015;3(7):451-467. [Abstract/Full-Text]
  26. Yousif NG, Ao L, Cleveland JC, Fullerton DA, Meng X. Aging augments myocardial inflammatory response to ischemia and reperfusion: an obligatory role of TLR4. Shock 2012;37:31-119. [Abstract]
  27. Rispens E, Bron A, Lee J, Fukumoto J. The pathophysiology of inflammation in cell injury. Pathophysiology of cell injury journal 2014;3(1):1-9. [Abstract/Full-Text]
  28. Sherian FM, Cole PG, Ramage D. Leukocyte adhesion to the coronary microvasculature during ischemia and reperfusion in an in vivo canine model. Circulation 1996;93:1784-1787. [PubMed]
  29. Natanson C, Eichenholz PW, Danner RL, et al. Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J Exp Med 1989;169:823-832. [PubMed]
  30. Cha J, Wang Z, Ao L, Zou N, Dinarello CA, Banerjee A, Fullerton DA, Meng X. Cytokines link Toll-like receptor 4 signaling to cardiac dysfunction after global myocardial ischemia. Ann Thorac Surg 2008;85:1678-1685. [PubMed]
  31. Dombrovskiy VY, Martin AA, Sunderram J, Paz HL. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med 2007;35:1244-1250. [PubMed]
  32. Fernandes CJ Jr, de Assuncao MS. Myocardial dysfunction in sepsis: a large, unsolved puzzle. Crit Care Res Pract 2012;2012:896430. [PubMed]
  33. Liquori ME, Christenson RH, Collinson PO, Defilippi CR. Cardiac biomarkers in heart failure. Clin Biochem 2014;47:327-337. [PubMed]
  34. Thron R, Andersson T, Lee K, Adrienne M. Over-expression of miR-486/miR-150 in sepsis: marker in myocardial depression function. American Journal of BioMedicine 2015;3(6):313-324. [Abstract/Full-Text]

READ THE FULL ARTICLE

Full-Text PDF

Thank you for visiting Pathophysiology of Cell Injury Journal. * = Required fields





Your Name (required)

Your Email (required)

Subject

Your Message

Print Friendly

Article download:
0

Doi: 10.18081/2378-5225-016-12/111-125
Cited by in Scopus
Research Article
Pathophysiology of Cell Injury Journal Volume 5, Issue 2, pages 111-125
Received June 03, 2016; accepted September 01, 2016; published October 09, 2016
How to cite this article
Yousif NG, Mohammad BI, Hadi N, Al-Dahhan MH, Al-khalidy S. N-acetylcysteine attenuated sepsis-induced cardiac depression: down-regulation of MMP-2 pathway in mice. Pathophysiology of Cell Injury Journal 2016;5:111-125.
Service

Email this link to a friend
Add article to my folders
Subscribe/Renew
Alert me when this article is cited
Add to portfolio
Contact with editor
Advertising

9066886592955137020Related: dollar tree syringe, swedish culture in early america, joe penna deutsche bank, what does stockings mean in lord of the flies, eastbourne district general hospital address, twin flame body sensations, floral fashion theme names, vietnam c ration cigarettes, boy names that mean toxic, matthew munoz missing, brown mackie college athletics staff directory, south carolina yacht club membership fees, eric eisner wife, macgregor funeral parlour, hollister size for 15 year old,Related: moral arguments of health and safety, kosovari live football, earlswood lakes haunted, sweet grapefruit strain, kim plath naturopathic doctor education, semi truck interior upholstery, timeless treasures fabrics tonga batiks, pancit canton calories 1 cup, craigslist rooms for rent woodland ca, jason cummings florida, what is the fastest way to heal leaky gut, modest swimwear uk next day delivery, , crypto com address verification failed, submit my music to smooth jazz radio station,Related: summoners war lushen damage calculator, trabajo de limpieza en escuelas ny, clapham rail disaster corporate manslaughter, recently solved cold cases 2021, psychological effects of never having a girlfriend, where can you marry your sister, toronto argonauts salary, physical ascension symptoms march 2021, mary shieler oak hill, west virginia, cher and nicolas cage relationship, how to fix unsupported image type google slides, where are bt call centres, houses for rent la grande, oregon, rocky marciano death cause, castillo funeral home obituaries,Related: conrad dc room service menu, funeral home funny quotes, bad credit apartments denver, i will wait for your further instructions email, winchester 1895 reproduction, susan blommaert virgin river, mobile homes for rent in thomson, ga, columbus ga police scanner, clc unit 2 dictionary, 20 million italian lire in us dollars, arjun malhotra net worth, paediatric endocrinologist westmead, ethiopian embassy washington dc yellow card application form, astro command center not detecting a40, fanfiction regina raised by rumple,Related: used stand up gas scooters for sale, which sentence is in the imperative mood, shield hero height chart, pros and cons of eating oysters, universal sewing machine serial number lookup, femoral artery bypass complications, he 177 model kit, usps mail recovery center address, van halen richfield coliseum, tarkov peak hours, fim approved helmets list, haskell sqrt integer, astro a40 discord setup, dating old school desks, sinden light gun,Related: used mobile homes for sale under $20,000, derek percy faeces, ryan mortuary obituaries, jim paxson wife, clearlake police department recent arrests, was there ever a whataburger in utah, crimson clover seed tractor supply, tate funeral home jasper, tn obituaries, minooka football coaching staff, elden ring secret medallion left, ancient rhodes government, is brent grimes still married, pre theatre restaurants near aldwych theatre, septuplets mccaughey father died, organ pipe cactus adaptations,Related: does lovelyskin sell fake products, wilder funeral home rich square, nc obituaries, cleveland elite volleyball club, 10 reasons not to move to asheville, quictent 10’x30 instructions, tydings bridge wind restrictions today, mutual of omaha dental fee schedule, clerk of the course horse racing jobs, house for sale in molynes road jamaica, marion county fl most wanted, nathan hale family tree, ratp dev self service, ted baker competitors analysis, how to set ulimit value in solaris 11 permanently, eric drummond geologist blind frog ranch,Related: california boat registration back fees, diplomat hotel happy hour, where do marine aviation mechanics get stationed, mortgage approved with conditions then denied, invega ruined my life vpxl, the counselor laura death, goviers platinum jubilee, college of computer science and engineering, how to change blackberry playbook os to android, 21 days after ovulation negative pregnancy test, eukanuba puppy feeding guide, bondi sands sunscreen physical or chemical, fairmount race track 2022 schedule, united road delivery receipt, coming late to office due to doctor appointment,Related: is gavin newsom related to nancy pelosi, mcdonald’s owner net worth, who owns prayer mountain in moravian falls nc, skullcap herb in spanish, mabel bassett correctional center jobs, quantumscape factory location, vittoria tire pressure chart, the force that pulls all objects toward each other, caudalie beauty elixir vs grape water, eir goddess offerings, visa software engineer interview process, racetrac relief manager duties, naperville obituaries 2022, 10,000 meters how many laps, brad gerstner wife,Related: motu ultralite mk5 sweetwater, what happens if you take gaviscon with antihistamine, labradorite lucid dreaming, man from reno ending explained, convert nominal to real dollars calculator, hellmann’s parmesan chicken in air fryer, couples spa downtown atlanta, 2799 broadway san francisco, setara hussainzada biography, what happened to west coast choppers, inteletravel back office login, 1891 km nnw from london, what pets are haram in islam, william lamar johnson cause of death, glenn kirschner family photo,Related: , albany county police blotter 2021, cheapest golf memberships in san diego, wendy harris obituary, les 30 pays les plus riches d’afrique 2021, 3 types of licence issued under the licensing act 2003, sullivan and cromwell salary partner, , nmls consumer access search, mosquito coast why are they on the run spoiler, john hopkins level of evidence, how to use chime temporary card, michael randall hood cause of death, golf driving range design standards, kevin wilson country singer,Related: mobile homes for rent in maine, st louis cardinals minority owners, silobration 2022 dates, chonda pierce grandchildren, dierya dk63 keyboard not typing, female image of god trafficking, theme park donation request, boca pointe country club membership fees, football clubs in finland looking for players, lewd words that start with s 5 letters, schneider national address in green bay, wi, territorial waters unclos, spencer carbery salary, alex reno son of mike reno, how to find qr code for microsoft outlook,Related: leader bank pavilion view from my seat, christendom college staff, white river amphitheater covid rules, agatha and the curse of ishtar parents guide, cpac conference 2023 location, asiana airlines economy basic vs flexi, how to read minutes of the previous meeting, calories in a lamb gyro with tzatziki sauce, boston residential exemption 2022, lateral meristem location, enbrel commercial erin actress, sony xav ax5500 equalizer settings, northwell spine center, trump approval rating rcp, kellan grady parents,Related: johnny was melbourne stockists, how to reset ao smith tankless water heater, cosmelan peel sacramento, why did melanie and derwin leave the game, james e casey ups biography, sccm client failed to signin bgb client with error 80090304, erana james ethnicity, pick up lines for the name meredith, ford 400m crankshaft for sale, scamps nightclub sutton, is christian leblanc related to matt leblanc, real colorado ecnl roster, mike bianco son louisville, elephants deli carrot cake recipe, sam houston softball: schedule 2022,Related: meadows funeral home, inc, weber county jail booking, what does toe ring mean sexually, gregory clark obituary california, ca dmv personalized plates check availability, silver springs, florida obituaries, general dynamics executive team, similarities between traditional and contemporary families, suzette rose daughter of jim rose, jump and bump kidney stone removal, mikki’s soul food owner dies, deborah barnes gospel singer biography, diamond lake school district 76 salary schedule, cool names for armor in minecraft, most romantic zodiac sign yourtango,Related: how to get rid of piggy taste in pork, raaf williamtown induction, christian ponder net worth 2020, auditor po box 637 peoria, il 61652, replace entune with android auto, jasmine roundtree julio jones, lymphedema papillomas, nancy haberman kushner, interior and exterior angles of triangles activity, troy mcclure statue location, why was walter baldwin replaced on the andy griffith show, grow crossword clue 8 letters, sierra canyon high school basketball stats, indigenous funeral notices qld, how tall is lieutenant governor mark robinson,Related: ct magazine best hair salons, cindy jacobs prophecy 2021, lawsuit against lgi homes, how many times has dwight yoakam been married, nicholas matthew bernthal, brett’s barn franklin tn address, how to cook 2 packages of knorr rice sides, islamic congratulations messages for graduation, county jail sentence calculator, my beer rebate offer number, why was the break from delta kappa epsilon especially difficult for founder bell, practicum goals and objectives examples for nurse educator, , naperville city swim meet 2021 results, canterbury academy staff list,Related: finlay christie comedian, goodbye my ni back to the lobby original, barrier for pachysandra, do criminal trespass warnings expire in texas, tattle life chateau diaries #102, dvla electronic counterpart check code uber, when will cricket get the galaxy s22, botw durability spreadsheet, david phelps wife, why is mozambique life expectancy so low, hawaii baptist academy uniform, was elvis presley italian, the statistics of inheritance packet, sonoma county supervisor districts, groodle puppies for sale qld,Related: aerosmith vegas residency 2022, joliet west superintendent, robert kwan singapore, congratulations message to a new police officer, mara seaweed net worth 2021, caireen celtic goddess, my boyfriend points out everything i do wrong, when a member is no longer qualified for advancement, pastor tim hill, does creatine make your face fat, ghost recon breakpoint how to change laser color, angela bofill daughter, best a cappella groups at yale, cordi fletcher, how to respond to grad school interview invitation,Related: niles harris biography, the beau ideal jessie pope, police incident in south elmsall, what did maggie cole say about her neighbours, aspan standards for phase 2 staffing, 12×24 is how many square feet, dymo rhino 4200 vs 5200, jefferson state community college student services, what happened on the courtney campbell causeway today, resin wicker repair supplies, what is a good ifit effort score, territory sales lead hershey salary, joshua educating the east end, what is legal environment in international business, ministry of health mauritius,Related: height predictor based on puberty stage, springfield model 951 410 parts, live music port aransas, komo news retired anchors, a flashing “don’t walk” pedestrian signal indicates that, fuddruckers milkshakes, do shiba inus get along with cats, how long was rick macci venus williams coach, obituaries talihina, oklahoma, gilbert high school football roster, how to open a cerave pump bottle, hematoma on buttocks after a fall, virginia regiments in the revolutionary war, accutite before and after, is golden corral ever going to reopen,Related: rose quartz to bring back ex, wv inspection sticker 2022, open enrollment school districts in texas, youth softball dayton ohio, imr 3031 load data, the north star poem metrical pattern, general conference talk on repentance, elden ring lazuli glintstone sword how to use, legacy sports complex phoenix, beaver dam maryland deaths, cardiff international pool cafe, the lory of augusta pet screening, brown soccer id camp 2022, inwood fire department, american lifan motorcycles,

Print Friendly, PDF & Email
Article download: 7,874