: In this article we provide an overview of the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion, and their possible role in alcoholic pancreatitis and pancreatic carcinoma. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. Some non-alcoholic compounds of beer, such as quercetin, resveratrol, ellagic acid or catechins, have been shown to be protective against experimentally induced pancreatitis by inhibiting pancreatic secretion, stellate cell activation or by reducing oxidative stress. Quercetin, ellagic acid and resveratrol also show anti-carcinogenic potential in vitro and in vivo. However, beer contains many more non-alcoholic ingredients. Their relevance in beer-induced functional alterations of pancreatic cells leading to pancreatitis and pancreatic cancer in humans needs to be further evaluated.
References
[1]
Niebergall-Roth, E; Harder, H; Singer, MV. A review: acute and chronic effects of ethanol and alcoholic beverages on the pancreatic exocrine secretion in vivo and in vitro. Alcohol Clin. Exp. Res?1998, 22, 1570–1583. 9802544
[2]
Schneider, A; Haas, SL; Singer, MV. Comprehensive Handbook of Alcohol Related Pathology; Preedy, VR, Watson, RR, Eds.; Elsevier Ltd: Amsterdam, The Netherland, 2005; Volume 2, pp. 577–597.
[3]
Chari, ST; Harder, H; Teyssen, S; Knodel, C; Riepl, RL; Singer, MV. Effect of beer, yeast-fermented glucose, and ethanol on pancreatic enzyme secretion in healthy human subjects. Dig. Dis. Sci?1996, 41, 1216–1224, doi:10.1007/BF02088240. 8654155
[4]
Hajnal, F; Flores, MC; Radley, S; Valenzuela, JE. Effect of alcohol and alcoholic beverages on meal-stimulated pancreatic secretion in humans. Gastroenterology?1990, 98, 191–196. 2293577
[5]
Hajnal, F; Flores, MC; Valenzuela, JE. Effect of alcohol and alcoholic beverages on nonstimulated pancreatic secretion in humans. Pancreas?1989, 4, 486–491, doi:10.1097/00006676-198908000-00014. 2762276
[6]
Singer, MV; Niebergall-Roth, E. Secretion from acinar cells of the exocrine pancreas: role of enteropancreatic reflexes and cholecystokinin. Cell Biol. Int?2009, 33, 1–9, doi:10.1016/j.cellbi.2008.09.008. 18948215
[7]
Leung, PS. The physiology of a local renin-angiotensin system in the pancreas. J. Physiol?2007, 580, 31–37, doi:10.1113/jphysiol.2006.126193. 17218353
[8]
Jaworek, J; Nawrot-Porabka, K; Leja-Szpak, A; Bonior, J; Szklarczyk, J; Kot, M; Konturek, SJ; Pawlik, WW. Melatonin as modulator of pancreatic enzyme secretion and pancreatoprotector. J. Physiol. Pharmacol?2007, 58, 65–80. 18212401
[9]
Singh, J; Pariente, JA; Salido, GM. The physiological role of histamine in the exocrine pancreas. Inflamm. Res?1997, 46, 159–165. 9197985
[10]
Chey, WY; Chang, T. Neural hormonal regulation of exocrine pancreatic secretion. Pancreatology?2001, 1, 320–335, doi:10.1159/000055831. 12120211
[11]
Gerloff, A; Singer, MV; Feick, P. Beer-induced pancreatic enzyme secretion: characterization of some signaling pathways and of the responsible nonalcoholic compounds. Alcohol Clin. Exp. Res?2009, 33, 1638–1645, doi:10.1111/j.1530-0277.2009.00995.x. 19519715
[12]
Gerloff, A; Singer, MV; Feick, P. Beer but not wine, hard liquors, or pure ethanol stimulates amylase secretion of rat pancreatic acinar cells in vitro. Alcohol Clin. Exp. Res?2009, 33, 1545–1554, doi:10.1111/j.1530-0277.2009.00983.x. 19485972
[13]
Dietrich, JB. AR4-2J cells: a model to study polypeptide hormone receptors. Biosci. Rep?1996, 16, 273–288, doi:10.1007/BF01855012. 8896787
[14]
Spanier, BW; Dijkgraaf, MG; Bruno, MJ. Epidemiology, aetiology and outcome of acute and chronic pancreatitis: An update. Best Pract. Res. Clin. Gastroenterol?2008, 22, 45–63, doi:10.1016/j.bpg.2007.10.007. 18206812
[15]
Chowdhury, P; Gupta, P. Pathophysiology of alcoholic pancreatitis: an overview. World J. Gastroenterol?2006, 12, 7421–7427. 17167828
[16]
Ammann, RW. The natural history of alcoholic chronic pancreatitis. Intern. Med?2001, 40, 368–375, doi:10.2169/internalmedicine.40.368. 11393404
[17]
Schneider, A; Whitcomb, DC; Singer, MV. Animal models in alcoholic pancreatitis—what can we learn? Pancreatology?2002, 2, 189–203, doi:10.1159/000058033. 12138724
[18]
Apte, MV; Pirola, RC; Wilson, JS. Individual susceptibility to alcoholic pancreatitis. J. Gastroenterol. Hepatol?2008, 23, S63–S68, doi:10.1111/j.1440-1746.2007.05287.x. 18336667
Haber, P; Wilson, J; Apte, M; Korsten, M; Pirola, R. Individual susceptibility to alcoholic pancreatitis: still an enigma. J. Lab. Clin. Med?1995, 125, 305–312. 7897296
[21]
Wilson, JS; Bernstein, L; McDonald, C; Tait, A; McNeil, D; Pirola, RC. Diet and drinking habits in relation to the development of alcoholic pancreatitis. Gut?1985, 26, 882–887, doi:10.1136/gut.26.9.882. 4029715
[22]
Nakamura, T; Ishikawa, A; Sekiguchi, S; Kuroda, M; Imazeki, H; Maruyama, K; Higuchi, S. Spirits Increase the Risk for Chronic Pancreatitis More Than Beer and Sake in 111 Japanese Alcoholics. Gastroenterology?2002, 122, A509.
[23]
Nakamura, Y; Kobayashi, Y; Ishikawa, A; Maruyama, K; Higuchi, S. Severe chronic pancreatitis and severe liver cirrhosis have different frequencies and are independent risk factors in male Japanese alcoholics. J. Gastroenterol?2004, 39, 879–887, doi:10.1007/s00535-004-1405-y. 15565408
[24]
Kristiansen, L; Gronbaek, M; Becker, U; Tolstrup, JS. Risk of pancreatitis according to alcohol drinking habits: a population-based cohort study. Am. J. Epidemiol?2008, 168, 932–937, doi:10.1093/aje/kwn222. 18779386
[25]
Piendl, A. Inhaltsstoffe des Bieres, dargestellt am Beispiel des Pilsener Lagerbieres. In Alkohol und Alkoholfolgekrankheiten, 2nd ed; Singer, MV, Teyssen, S, Eds.; Springer Verlag: Berlin, Germany, 2005; pp. 65–69.
[26]
Szabolcs, A; Varga, IS; Varga, C; Berko, A; Kaszaki, J; Letoha, T; Tiszlavicz, L; Sari, R; Lonovics, J; Takacs, T. Beneficial effect of resveratrol on cholecystokinin-induced experimental pancreatitis. Eur. J. Pharmacol?2006, 532, 187–193, doi:10.1016/j.ejphar.2006.01.055. 16499907
[27]
Ma, ZH; Ma, QY; Wang, LC; Sha, HC; Wu, SL; Zhang, M. Effect of resveratrol on peritoneal macrophages in rats with severe acute pancreatitis. Inflamm. Res?2005, 54, 522–527, doi:10.1007/s00011-005-1388-z. 16389574
[28]
Meng, Y; Ma, QY; Kou, XP; Xu, J. Effect of resveratrol on activation of nuclear factor kappa-B and inflammatory factors in rat model of acute pancreatitis. World J. Gastroenterol?2005, 11, 525–528. 15641139
[29]
Wang, L; Ma, Q; Chen, X; Sha, H; Ma, Z. Effects of resveratrol on calcium regulation in rats with severe acute pancreatitis. Eur. J. Pharmacol?2008, 580, 271–276, doi:10.1016/j.ejphar.2007.10.068. 18031730
[30]
Warzecha, Z; Dembinski, A; Ceranowicz, P; Konturek, S; Tomaszewska, R; Stachura, J; Nakamura, T; Konturek, PC. Inhibition of cyclooxygenase-2 reduces the protective effect of hepatocyte growth factor in experimental pancreatitis. Eur. J. Pharmacol?2004, 486, 107–119, doi:10.1016/j.ejphar.2003.12.015. 14751415
[31]
Li, ZD; Ma, QY; Wang, CA. Effect of resveratrol on pancreatic oxygen free radicals in rats with severe acute pancreatitis. World J. Gastroenterol?2006, 12, 137–140. 16440434
[32]
Lawinski, M; Sledzinski, Z; Kubasik-Juraniec, J; Spodnik, JH; Wozniak, M; Boguslawski, W. Does resveratrol prevent free radical-induced acute pancreatitis? Pancreas?2005, 31, 43–47, doi:10.1097/01.mpa.0000163021.40607.20. 15968246
[33]
Takabayashi, F; Harada, N; Hara, Y. The effects of green tea catechins (Polyphenon) on DL-ethionine-induced acute pancreatitis. Pancreas?1995, 11, 127–131, doi:10.1097/00006676-199508000-00003. 7479668
[34]
Takabayashi, F; Harada, N. Effects of green tea catechins (Polyphenon 100) on cerulein-induced acute pancreatitis in rats. Pancreas?1997, 14, 276–279, doi:10.1097/00006676-199704000-00009. 9094158
[35]
Takabayashi, F; Harada, N; Tahara, S; Kaneko, T; Hara, Y. Effect of green tea catechins on the amount of 8-hydroxydeoxyguanosine (8-OHdG) in pancreatic and hepatic DNA after a single administration of N-nitrosobis(2-oxopropyl)amine (BOP). Pancreas?1997, 15, 109–112, doi:10.1097/00006676-199708000-00001. 9260194
[36]
Takabayashi, F; Tahara, S; Kaneko, T; Harada, N. Effect of green tea catechins on oxidative DNA damage of hamster pancreas and liver induced by N-Nitrosobis(2-oxopropyl)amine and/or oxidized soybean oil. Biofactors?2004, 21, 335–337, doi:10.1002/biof.552210165. 15630222
[37]
Bhagat, L; Singh, VP; Hietaranta, AJ; Agrawal, S; Steer, ML; Saluja, AK. Heat shock protein 70 prevents secretagogue-induced cell injury in the pancreas by preventing intracellular trypsinogen activation. J. Clin. Invest?2000, 106, 81–89, doi:10.1172/JCI8706. 10880051
[38]
Maxwell, S; Cruickshank, A; Thorpe, G. Red wine and antioxidant activity in serum. Lancet?1994, 344, 193–194. 7912786
[39]
Apte, MV; Pirola, RC; Wilson, JS. Battle-scarred pancreas: Role of alcohol and pancreatic stellate cells in pancreatic fibrosis. J. Gastroenterol. Hepatol?2006, 21, S97–S101, doi:10.1111/j.1440-1746.2006.04587.x. 16958684
[40]
Masamune, A; Satoh, M; Kikuta, K; Suzuki, N; Satoh, K; Shimosegawa, T. Ellagic acid blocks activation of pancreatic stellate cells. Biochem. Pharmacol?2005, 70, 869–878, doi:10.1016/j.bcp.2005.06.008. 16023081
Genkinger, JM; Spiegelman, D; Anderson, KE; Bergkvist, L; Bernstein, L; van den Brandt, PA; English, DR; Freudenheim, JL; Fuchs, CS; Giles, GG; Giovannucci, E; Hankinson, SE; Horn-Ross, PL; Leitzmann, M; Mannisto, S; Marshall, JR; McCullough, ML; Miller, AB; Reding, DJ; Robien, K; Rohan, TE; Schatzkin, A; Stevens, VL; Stolzenberg-Solomon, RZ; Verhage, BA; Wolk, A; Ziegler, RG; Smith-Warner, SA. Alcohol intake and pancreatic cancer risk: a pooled analysis of fourteen cohort studies. Cancer Epidemiol. Biomarkers Prev?2009, 18, 765–776, doi:10.1158/1055-9965.EPI-08-0880. 19258474
[43]
Lowenfels, AB; Maisonneuve, P; Cavallini, G; Ammann, RW; Lankisch, PG; Andersen, JR; Dimagno, EP; Andren-Sandberg, A; Domellof, L. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N. Engl. J. Med?1993, 328, 1433–1437, doi:10.1056/NEJM199305203282001. 8479461
[44]
Nothlings, U; Murphy, SP; Wilkens, LR; Henderson, BE; Kolonel, LN. Flavonols and pancreatic cancer risk: the multiethnic cohort study. Am. J. Epidemiol?2007, 166, 924–931, doi:10.1093/aje/kwm172. 17690219
[45]
Mouria, M; Gukovskaya, AS; Jung, Y; Buechler, P; Hines, OJ; Reber, HA; Pandol, SJ. Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis. Int. J. Cancer?2002, 98, 761–769, doi:10.1002/ijc.10202. 11920648
[46]
Edderkaoui, M; Odinokova, I; Ohno, I; Gukovsky, I; Go, VL; Pandol, SJ; Gukovskaya, AS. Ellagic acid induces apoptosis through inhibition of nuclear factor kappa B in pancreatic cancer cells. World J. Gastroenterol?2008, 14, 3672–3680, doi:10.3748/wjg.14.3672. 18595134
[47]
Ding, XZ; Adrian, TE. Resveratrol inhibits proliferation and induces apoptosis in human pancreatic cancer cells. Pancreas?2002, 25, e71–e76, doi:10.1097/00006676-200211000-00024. 12409844
[48]
Yamagishi, M; Natsume, M; Osakabe, N; Nakamura, H; Furukawa, F; Imazawa, T; Nishikawa, A; Hirose, M. Effects of cacao liquor proanthocyanidins on PhIP-induced mutagenesis in vitro, and in vivo mammary and pancreatic tumorigenesis in female Sprague-Dawley rats. Cancer Lett?2002, 185, 123–130, doi:10.1016/S0304-3835(02)00276-8. 12169385
[49]
Sun, W; Wang, W; Kim, J; Keng, P; Yang, S; Zhang, H; Liu, C; Okunieff, P; Zhang, L. Anti-cancer effect of resveratrol is associated with induction of apoptosis via a mitochondrial pathway alignment. Adv. Exp. Med. Biol?2008, 614, 179–186. 18290328