nach oben

Langenbeck's Archives of Surgery

Erschienen in:

01.07.2008 | Original Article

A cell-based approach to study changes in the pancreas following nicotine exposure in an animal model of injury

verfasst von: Parimal Chowdhury, Azida Walker

Erschienen in: Langenbeck's Archives of Surgery | Ausgabe 4/2008

Einloggen, um Zugang zu erhalten

Abstract

Background

Cigarette smoking is a recognized risk factor for the induction of pancreatic diseases and is suspected to play a major role in the development of pancreatic cancer in smokers.

Materials and methods

This study was designed to characterize the mechanisms of nicotine-induced injury to the pancreas. AR42Jcells, a stable mutant pancreatic tumor cell line, was chosen for the study because of its stability in culture media and also because of its known secretory capacity, which is like that of a normal pancreatic acinar cell. It is hypothesized that nicotine-induced effects on the pancreas are triggered by oxidative stress induced in pancreatic acinar cell via oxidative stress signaling pathways.

Results

The results from our study showed that, in vitro, nicotine induced generation of oxygen free radicals measured as malondialdehyde, an end product of lipid peroxidation. Treatment of AR42J cells with nicotine induced p-ERK 1/2 activation as confirmed by Western blot and immunofluorescence imaging of cytoplasmic localization of mitogen-activated protein kinase (MAPK) signals. Nicotine enhanced AR42J cell proliferation and cholecystokinin-stimulated amylase release in AR42J cells. These effects of nicotine were confirmed by simultaneous studies conducted on the same cells by hydrogen peroxide, a known oxidative biomarker. Allopurinol, a XOD inhibitor, suppressed these effects induced by nicotine and H₂O₂ with the exception that cholecystokinin-stimulated amylase release by H₂O₂ remained unaltered when AR42J cells were preincubated with allopurinol. These results suggest that nicotine-induced effects on pancreatic acinar cells were associated with generation of oxyradical mediated via the XOD pathway. The results have a direct impact on cell proliferation, MAPK signaling, and acinar cell function.

Conclusion

We conclude that nicotine induces oxidative stress in pancreatic acinar cells and that these events trigger pathophysiological changes in the pancreas, leading to increased cell proliferation and injury.

Talamini G, Bassi C, Falconi M, Sartori N, Salvia R, Rigo L, Castagnini A, Di Francesco V, Frulloni L, Bovo P, Vaona B, Angelini G, Vantini I, Cavallini G, Pederzoli P (1999) Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer. Dig Dis Sci 44:1303–1311PubMedCrossRef

Lin Y, Tamakoshi A, Hayakawa T, Ogawa M, Ohno Y (2000) Cigarette smoking as a risk factor for chronic pancreatitis: a case-control study in Japan. Research Committee on Intractable Pancreatic Diseases. Pancreas 21:109–114PubMedCrossRef

Maritz GS, Burger B (1992) The influence of maternal nicotine exposure on neonatal lung carbohydrate metabolism. Cell Biol Int Rep 16:1229–1236PubMedCrossRef

Bose C, Zhang H, Udupa KB, Chowdhury P (2005) Activation of p-ERK1/2 by nicotine in pancreatic tumor cell line AR42J: effects on proliferation and secretion. Am J Physiol Gastrointest Liver Physiol 289:G926–G934PubMedCrossRef

Chowdhury P, MacLeod S, Udupa KB, Rayford PL (2002) Pathophysiological effects of nicotine on the pancreas: an update. Exp Biol Med (Maywood) 227:445–454

Rayford PL, Chowdhury P (2001) Mecamylamine, a nicotinic receptor channel antagonist, affects amylase secretion by isolated pancreatic acinar cells. J Assoc Acad Minor Phys 12:105–108PubMed

Chowdhury P, Hosotani R, Chang L, Rayford PL (1990) Metabolic and pathologic effects of nicotine on gastrointestinal tract and pancreas of rats. Pancreas 5:222–229PubMedCrossRef

Chowdhury P (2003) An exploratory study on the development of an animal model of pancreatitis following nicotine exposure. Tob Induced Dis 1(3):213–217CrossRef

Wetscher GJ, Bagchi M, Bagchi D, Perdikis G, Hinder PR, Glaser K, Hinder RA (1995) Free radical production in nicotine treated pancreatic tissue. Free Radic Biol Med 18:877–882PubMedCrossRef

10.

Kalpana C, Menon VP (2004) Curcumin ameliorates oxidative stress during nicotine-induced lung toxicity in Wistar rats. Ital J Biochem 53:82–86PubMed

11.

Piperakis SM, Visvardis EE, Sagnou M, Tassiou AM (1998) Effects of smoking and aging on oxidative DNA damage of human lymphocytes. Carcinogenesis 19:695–698PubMedCrossRef

12.

Park BK, Chung JB, Lee JH, Suh JH, Park SW, Song SY, Kim H, Kim KH, Kang JK (2003) Role of oxygen free radicals in patients with acute pancreatitis. World J Gastroenterol 9:2266–2269PubMed

13.

Ganesh PC, Sreejayan, Rao MN (1999) Evidence for oxidant stress in chronic pancreatitis. Indian J Gastroenterol 18:156–157

14.

Sanfey H, Bulkley GB, Cameron JL (1985) The pathogenesis of acute pancreatitis. The source and role of oxygen-derived free radicals in three different experimental models. Ann Surg 201:633–639PubMedCrossRef

15.

Schoenberg MH, Buchler M, Beger HG (1994) Oxygen radicals in experimental acute pancreatitis. Hepatogastroenterology 41:313–319PubMed

16.

Sweiry JH, Mann GE (1996) Role of oxidative stress in the pathogenesis of acute pancreatitis. Scand J Gastroenterol Suppl 219:10–15PubMedCrossRef

17.

Czako L, Takacs T, Varga IS, Tiszlavicz L, Hai DQ, Hegyi P, Matkovics B, Lonovics J (1998) Involvement of oxygen-derived free radicals in L-arginine-induced acute pancreatitis. Dig Dis Sci 43:1770–1777PubMedCrossRef

18.

Klein AS, Joh JW, Rangan U, Wang D, Bulkley GB (1996) Allopurinol: discrimination of antioxidant from enzyme inhibitory activities. Free Radic Biol Med 21:713–717PubMedCrossRef

19.

Wisner J, Green D, Ferrell L, Renner I (1988) Evidence for a role of oxygen derived free radicals in the pathogenesis of caerulein induced acute pancreatitis in rats. Gut 29:1516–1523PubMedCrossRef

20.

Das DK, Engelman RM, Clement R, Otani H, Prasad MR, Rao PS (1987) Role of xanthine oxidase inhibitor as free radical scavenger: a novel mechanism of action of allopurinol and oxypurinol in myocardial salvage. Biochem Biophys Res Commun 148:314–319PubMedCrossRef

21.

Grisham MB, Hernandez LA, Granger DN (1986) Xanthine oxidase and neutrophil infiltration in intestinal ischemia. Am J Physiol 251:G567–G574PubMed

22.

Moorhouse PC, Grootveld M, Halliwell B, Quinlan JG, Gutteridge JM (1987) Allopurinol and oxypurinol are hydroxyl radical scavengers. FEBS Lett 213:23–28PubMedCrossRef

23.

Fox IH (1976) Inborn errors of purine and pyrimidine metabolism. Clin Perinatol 3:133–140PubMed

24.

Peterson DA, Kelly B, Gerrard JM (1986) Allopurinol can act as an electron transfer agent. Is this relevant during reperfusion injury? Biochem Biophys Res Commun 137:76–79PubMedCrossRef

25.

Mikulikova D, Bosmansky K, Bosak V, Ondrasik M (1989) The effect of allopurinol on lysosomal enzyme release. Z Rheumatol 48:26–29PubMed

26.

Parks DA, Granger DN (1986) Contributions of ischemia and reperfusion to mucosal lesion formation. Am J Physiol 250:G749–G753PubMed

27.

Sawamura M, Sun SH, Ozaki K, Ishikawa J, Ukeda H (1999) Inhibitory effects of citrus essential oils and their components on the formation of N-nitrosodimethylamine. J Agric Food Chem 47:4868–4872PubMedCrossRef

28.

Shahraki A, Fukunari A, Stone TW (2004) The mechanism of inhibition by xanthine of adenosine A1-receptor responses in rat hippocampus. Neurosci Lett 365:162–166PubMedCrossRef

29.

Valencia A, Moran J (2004) Reactive oxygen species induce different cell death mechanisms in cultured neurons. Free Radic Biol Med 36:1112–1125PubMedCrossRef

30.

Fatokun AA, Stone TW, Smith RA (2007) Hydrogen peroxide mediates damage by xanthine and xanthine oxidase in cerebellar granule neuronal cultures. Neurosci Lett 416:34–38PubMedCrossRef

31.

Chiarugi P (2003) Reactive oxygen species as mediators of cell adhesion. Ital J Biochem 52:28–32PubMed

32.

Zienolddiny S, Ryberg D, Haugen A (2000) Induction of microsatellite mutations by oxidative agents in human lung cancer cell lines. Carcinogenesis 21:1521–1526PubMedCrossRef

33.

Christophe J (1994) Pancreatic tumoral cell line AR42J: an amphicrine model. Am J Physiol 266:G963–G971PubMed

34.

Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72:248–254PubMedCrossRef

35.

Jung DH (1980) Preparation and application of Procion Yellow starch for amylase assay. Clin Chim Acta 100:7–11PubMedCrossRef

36.

Ogawa Y, Kobayashi T, Nishioka A, Kariya S, Ohnishi T, Hamasato S, Seguchi H, Yoshida S (2004) Reactive oxygen species-producing site in radiation-induced apoptosis of human peripheral T cells: involvement of lysosomal membrane destabilization. Int J Mol Med 13:69–73PubMed

37.

Riley PA (1994) Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radiat Biol 65:27–33PubMedCrossRef

38.

Iijima R, Takahashi H, Namme R, Ikegami S, Yamazaki M (2004) Novel biological function of sialic acid (N-acetylneuraminic acid) as a hydrogen peroxide scavenger. FEBS Lett 561:163–166PubMedCrossRef

39.

Guan W, Osanai T, Kamada T, Hanada H, Ishizaka H, Onodera H, Iwasa A, Fujita N, Kudo S, Ohkubo T, Okumura K (2003) Effect of allopurinol pretreatment on free radical generation after primary coronary angioplasty for acute myocardial infarction. J Cardiovasc Pharmacol 41:699–705PubMedCrossRef

40.

Fridovich I (1986) Biological effects of the superoxide radical. Arch Biochem Biophys 247:1–11PubMedCrossRef

41.

Fujita T (2002) Formation and removal of reactive oxygen species, lipid peroxides and free radicals, and their biological effects. Yakugaku Zasshi 122:203–218PubMedCrossRef

42.

Yamamoto Y, Ogino K, Igawa G, Matsuura T, Kaetsu Y, Sugihara S, Matsubara K, Miake J, Hamada T, Yoshida A, Igawa O, Yamamoto T, Shigemasa C, Hisatome I (2006) Allopurinol reduces neointimal hyperplasia in the carotid artery ligation model in spontaneously hypertensive rats. Hypertens Res 29:915–921PubMedCrossRef

43.

Inkster ME, Cotter MA, Cameron NE (2007) Treatment with the xanthine oxidase inhibitor, allopurinol, improves nerve and vascular function in diabetic rats. Eur J Pharmacol 561:63–71PubMedCrossRef

44.

Spahr L, Bresson-Hadni S, Amann P, Kern I, Golaz O, Frossard JL, Hadengue A (2007) Allopurinol, oxidative stress and intestinal permeability in patients with cirrhosis: an open-label pilot study. Liver Int 27:54–60PubMedCrossRef

45.

Lee WY, Lee SM (2006) Synergistic protective effect of ischemic preconditioning and allopurinol on ischemia/reperfusion injury in rat liver. Biochem Biophys Res Commun 349:1087–1093PubMedCrossRef

46.

Vincent AM, Stevens MJ, Backus C, McLean LL, Feldman EL (2005) Cell culture modeling to test therapies against hyperglycemia-mediated oxidative stress and injury. Antioxid Redox Signal 7:1494–1506PubMedCrossRef

47.

Heunks LM, Vina J, van Herwaarden CL, Folgering HT, Gimeno A, Dekhuijzen PN (1999) Xanthine oxidase is involved in exercise-induced oxidative stress in chronic obstructive pulmonary disease. Am J Physiol 277:R1697–R1704PubMed

48.

Baud O, Greene AE, Li J, Wang H, Volpe JJ, Rosenberg PA (2004) Glutathione peroxidase-catalase cooperativity is required for resistance to hydrogen peroxide by mature rat oligodendrocytes. J Neurosci 24:1531–1540PubMedCrossRef

49.

Meiners S, Ludwig A, Lorenz M, Dreger H, Baumann G, Stangl V, Stangl K (2006) Nontoxic proteasome inhibition activates a protective antioxidant defense response in endothelial cells. Free Radic Biol Med 40:2232–2241PubMedCrossRef

50.

Martindale JL, Holbrook NJ (2002) Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol 192:1–15PubMedCrossRef

51.

Yang B, Oo TN, Rizzo V (2006) Lipid rafts mediate H₂O₂ prosurvival effects in cultured endothelial cells. FASEB J 20:1501–1503PubMedCrossRef

52.

Zhou Y, Wang Q, Evers BM, Chung DH (2005) Signal transduction pathways involved in oxidative stress-induced intestinal epithelial cell apoptosis. Pediatr Res 58:1192–1197PubMedCrossRef

53.

Watanabe N, Zmijewski JW, Takabe W, Umezu-Goto M, Le Goffe C, Sekine A, Landar A, Watanabe A, Aoki J, Arai H, Kodama T, Murphy MP, Kalyanaraman R, Darley-Usmar VM, Noguchi N (2006) Activation of mitogen-activated protein kinases by lysophosphatidylcholine-induced mitochondrial reactive oxygen species generation in endothelial cells. Am J Pathol 168:1737–1748PubMedCrossRef

54.

Abdulnour RE, Peng X, Finigan JH, Han EJ, Hasan EJ, Birukov KG, Reddy SP, Watkins JE, III, Kayyali US, Garcia JG, Tuder RM, Hassoun PM (2006) Mechanical stress activates xanthine oxidoreductase through MAP kinase-dependent pathways. Am J Physiol Lung Cell Mol Physiol 291:L345–L353PubMedCrossRef

55.

Vorbach C, Harrison R, Capecchi MR (2003) Xanthine oxidoreductase is central to the evolution and function of the innate immune system. Trends Immunol 24:512–517PubMedCrossRef

56.

Zhang J, Jin N, Liu Y, Rhoades RA (1998) Hydrogen peroxide stimulates extracellular signal-regulated protein kinases in pulmonary arterial smooth muscle cells. Am J Respir Cell Mol Biol 19:324–332PubMed

57.

Song HJ, Lee TS, Jeong JH, Min YS, Shin CY, Sohn UD (2005) Hydrogen peroxide-induced extracellular signal-regulated kinase activation in cultured feline ileal smooth muscle cells. J Pharmacol Exp Ther 312:391–398PubMedCrossRef

58.

Granados MP, Salido GM, Pariente JA, Gonzalez A (2005) Effect of H₂O₂ on CCK-8 evoked changes in mitochondrial activity in isolated mouse pancreatic acinar cells. Biol Cell 97:847–856PubMedCrossRef

59.

Weitberg AB, Corvese D (1993) Oxygen radicals potentiate the genetic toxicity of tobacco-specific nitrosamines. Clin Genet 43:88–91PubMed

Titel: A cell-based approach to study changes in the pancreas following nicotine exposure in an animal model of injury
verfasst von: Parimal Chowdhury
Azida Walker
Publikationsdatum: 01.07.2008
Verlag: Springer-Verlag
Erschienen in: Langenbeck's Archives of Surgery / Ausgabe 4/2008
Print ISSN: 1435-2443
Elektronische ISSN: 1435-2451
DOI: https://doi.org/10.1007/s00423-007-0267-1

Neu im Fachgebiet Chirurgie

Vorsicht, erhöhte Blutungsgefahr nach PCI!

10.05.2024 Koronare Herzerkrankung Nachrichten

Nach PCI besteht ein erhöhtes Blutungsrisiko, wenn die Behandelten eine verminderte linksventrikuläre Ejektionsfraktion aufweisen. Das Risiko ist umso höher, je stärker die Pumpfunktion eingeschränkt ist.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Deutlich weniger Infektionen: Wundprotektoren schützen!

08.05.2024 Postoperative Wundinfektion Nachrichten

Der Einsatz von Wundprotektoren bei offenen Eingriffen am unteren Gastrointestinaltrakt schützt vor Infektionen im Op.-Gebiet – und dient darüber hinaus der besseren Sicht. Das bestätigt mit großer Robustheit eine randomisierte Studie im Fachblatt JAMA Surgery.

Chirurginnen und Chirurgen sind stark suizidgefährdet

07.05.2024 Suizid Nachrichten

Der belastende Arbeitsalltag wirkt sich negativ auf die psychische Gesundheit der Angehörigen ärztlicher Berufsgruppen aus. Chirurginnen und Chirurgen bilden da keine Ausnahme, im Gegenteil.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Aktuelle BDC Leitlinien-Webinare

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare

CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare

CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske

Dr. med. Benjamin Meyknecht

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare

CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric

Springer Medizin

Abstract

Background

Materials and methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2008

Simple segmental resection of the second portion of the duodenum for the treatment of gastrointestinal stromal tumors

Clinical Pathways in surgery—should we introduce them into clinical routine? A review article

Duodenum-preserving total pancreatic head resection for cystic neoplasm—a limited but cancer-preventive procedure

Solitary fibrous tumour of the liver with IGF-II-related hypoglycaemia. A case report

Hepatobiliary resection with inferior vena cava resection and reconstruction using an autologous patch graft for intrahepatic cholangiocarcinoma

Impact of stapled haemorrhoidopexy on stool continence and anorectal function—long-term follow-up of 242 patients

Update Chirurgie