Deneysel Akut Pankreatit Oluşturulan Ratlarda Lipit Profil Üzerine Timokinonun Etkileri

Year 2022, Volume: 11 Issue: 1, 58 - 65, 15.05.2022

Sevim Kanaç Deniz Uluışık , Ercan Keskin

https://doi.org/10.31196/huvfd.1066860

Abstract

Çalışmada serulein ile akut pankreatit oluşturulan ratlarda timokinonun lipit profil üzerine olası etkilerinin belirlenmesi amaçlanmıştır. Çalışma süresi olan 9 gün boyunca kontrol grubuna (K) herhangi bir uygulama yapılmadı. Timokinon grubundaki (TQ) hayvanlara 9 gün süre ile günde 20 mg/kg timokinon intraperitoneal olarak verilirken, akut pankreatit grubundaki (AP) hayvanlarda araştırmanın 7. gününde 50 μg/kg ve 2 saat sonra 25 μg/kg seruleinin intraperitoneal olarak uygulanmasıyla akut pankreatit oluşturuldu. Akut pankreatit+timokinon grubunda ise (AP+TQ) günde 20 mg/kg olmak üzere 9 gün süre ile intraperitoneal olarak timokinon verilen hayvanlarda araştırmanın 7. gününde timokinon uygulamasından 2 saat sonra 50 μg/kg ve bundan 2 saat sonra 25 μg/kg seruleinin intraperitoneal olarak uygulanmasıyla akut pankreatit oluşturuldu. Bütün hayvanlardan alınan kan örneklerinde Lipaz, Amilaz, Trigliserit, Total Kolesterol, Düşük dansiteli lipoprotein (LDL-kolesterol) ve Yüksek dansiteli lipoprotein (HDL-kolesterol) düzeyleri belirlendi. Deneysel akut pankreatit oluşturulan ratlarda amilaz ve lipaz düzeyleri kontrol grubuna göre anlamlı olarak yüksek olduğu belirlendi (p<0.05). Akut pankreatit oluşturulan grupta yüksek olan bu enzim düzeylerinin timokinon uygulanan akut pankreatitli ratlarda önemli oranda baskılandığı belirlendi (p<0.05). Çalışmada serulein ile oluşturulan deneysel akut pankreatite bağlı olarak plazma trigliserit ve total kolesterol düzeylerinin kontrol grubuna göre önemli oranda yüksek olduğu belirlendi (p<0.05). Akut pankreatitli ratlarda LDL-kolesterol düzeyi kontrol grubuna göre anlamlı oranda yüksek bulunurken (p<0.05), HDL-kolesterol düzeyi ise anlamlı oranda düşüktü (p<0.05). Timokinon uygulanan akut pankreatitli ratların total kolesterol ve LDL-kolesterol düzeylerinin akut pankreatitli gruba göre anlamlı oranda düşük olduğu belirlendi (p<0.05). Sonuç olarak, plazma lipit parametreleri ve bazı enzim düzeylerindeki farklılıklar dikkate alındığında timokinonun akut pankreatit üzerine olumlu etkileri olduğu kanaatine varıldı.

Keywords

Serulein, Timokinon, Lipit Profil, Rat

Supporting Institution

Selçuk Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü

Project Number

19202065

Thanks

Bu araştırma Selçuk Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü tarafından 19202065 proje numarası ile desteklenmiştir.

Effects of Thymoquinone on Lipid Profile in Rats with Experimentally Acute Pancreatitis

Abstract

This study aimed to determine the possible effects of thymoquinone on lipid profile in rats with cerulein-induced acute pancreatitis. No application was made to the control group (K) during the study period of nine days. The thymoquinone group (TQ) animals were administered 20 mg/kg of thymoquinone daily for nine days. In the acute pancreatitis group (AP), acute pancreatitis was induced by intraperitoneal cerulein administration of 50 μg/kg and 2 hours later, 25 μg/kg on the seventh day of the study. Animals in the acute pancreatitis+thymoquinone group (AP+TQ) were intraperitoneally administered 20 mg/kg of thymoquinone daily for nine days. On the seventh day of the study, acute pancreatitis was induced by intraperitoneal administration of 50 μg/kg and 2 hours later 25 μg/kg of cerulein after 2 hours from thymoquinone administration. In blood samples taken from all animals, Lipase, Amylase, Triglyceride, Total Cholesterol, low-density lipoprotein (LDL-cholesterol), and high-density lipoprotein (HDL-cholesterol) levels were determined. The amylase and lipase levels of rats with acute experimental pancreatitis were significantly higher than the control group (p<0.05). It was determined that these enzyme levels, which were high in the acute pancreatitis group, were significantly suppressed in rats with acute pancreatitis treated with thymoquinone (p<0.05). The increase in plasma triglyceride and total cholesterol levels due to acute experimental pancreatitis induced with cerulein was significant compared to the control group (p<0.05). LDL-cholesterol level of rats with acute pancreatitis was found to be significantly higher than the control group (p<0.05), while HDL-cholesterol level was significantly lower (p<0.05). The total cholesterol and LDL-cholesterol levels of rats with acute pancreatitis treated with thymoquinone were significantly lower than those of the acute pancreatitis group (p<0.05). In conclusion, in light of differences in plasma lipid parameters and some enzyme levels, it was considered that thymoquinone has positive effects on acute pancreatitis.

Keywords

Cerulein, Thymoquinone, Lipid Profile, Rats

Project Number

19202065

References

• Abdel-Daim MM, Abo El-Ela FI, Alshahrani FK, Bin-Jumah M, Al-Zharani M, Almutairi B, Alyousif MS, Bungau S, Aleya L, Alkahtani S, 2020: Protective effects of thymoquinone against acrylamide-induced liver, kidney and brain oxidative damage in rats. Environ Sci Pollut Res Int, 27 (30), 37709-37717. doi: 10.1007/s11356-020-09516-3.
• Ahmad S, Beg ZH, 2013: Hypolipidemic and antioxidant activities of thymoquinone and limonene in atherogenic suspension fed rats. Food Chem, 138 (2-3), 1116-1124.
• Al-Naqeep G, Al-Zubairi AS, Ismail M, Amom ZH, Esa NM, 2011: Antiatherogenic potential of Nigella sativa seeds and oil in diet-induced hypercholesterolemia in rabbits. Evid Based Complement Alternat Med, 2011, 213628. doi: 10.1093/ecam/neq071.
• Al-Naqeep G, Ismail M, Allaudin Z, 2009: Regulation of low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase gene expression by thymoquinone-rich fraction and thymoquinone in HepG2 cells. Lifestyle Genomics, 2 (4-5), 163-172.
• Andican G, Gelisgen R, Unal E, Tortum OB, Dervisoglu S, Karahasanoglu T, Burçak G, 2005: Oxidative stress and nitric oxide in rats with alcohol-induced acute pancreatitis. World J Gastroenterol, 11 (15), 2340-2345. doi: 10.3748/wjg.v11.i15.2340.
• Asgary S, Ghannadi A, Dashti G, Helalat A, Sahebkar A, Najafi S, 2013: Nigella sativa L. improves lipid profile and prevents atherosclerosis: Evidence from an experimental study on hypercholesterolemic rabbits. J Funct Foods, 5 (1), 228-234.
• Ashraf SS, Rao MV, Kaneez FS, Qadri S, Al-Marzouqi AH, Chandranath IS, Adem A, 2011: Nigella sativa extract as a potent antioxidant for petrochemical-induced oxidative stress. J Chromatogr Sci, 49 (4), 321-326. doi: 10.1093/chrsci/49.4.321.
• Badary OA, Abdel-Naim AB, Abdel-Wahab MH, Hamada FM, 2000: The influence of thymoquinone on doxorubicin-induced hyperlipidemic nephropathy in rats. Toxicology, 143 (3), 219-226.
• Badary OA, Taha RA, Gamal el-Din AM, Abdel-Wahab MH, 2003: Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol, 26 (2), 87-98. doi: 10.1081/dct-120020404.
• Baggio G, Manzato E, Gabelli C, Fellin R, Martini S, Enzi GB, Verlato F, Baiocchi M, Sprecher D, Kashyap M, 1986: Apolipoprotein C-II deficiency syndrome. Clinical features, lipoprotein characterization, lipase activity, and correction of hypertriglyceridemia after apolipoprotein C-II administration in two affected patients. J Clin Invest, 77 (2), 520-527.
• Bamosa A, Ali BA, Al-Hawsawi ZA, 2002: The effect of thymoquinone on blood lipids in rats. Indian J Physiol Pharmacol, 46 (2), 195-201. Banks PA, Freeman ML, Gastroenterology PPCotACo, 2006: Practice guidelines in acute pancreatitis. Official Journal of the American College of Gastroenterology ACG, 101 (10), 2379-400.
• Bansod S, Chilvery S, Saifi MA, Das TJ, Tag H, Godugu C, 2021: Borneol protects against cerulein‐induced oxidative stress and inflammation in acute pancreatitis mice model. Environ Toxicol, 36 (4), 530-539.
• Bhatti IU, Rehman FU, Khan MA, Marwat SK, 2009: Effect of prophetic medicine Kalonji (Nigella sativa L.) on lipid profile of human beings: an in vivo approach. World Appl Sci J, 6(8), 1053-1057.
• Bugdaci MS, Sokmen M, Zuhur SS, Altuntas Y, 2011: Lipid profile changes and importance of low serum α-lipoprotein fraction (high-density lipoprotein) in cases with acute pancreatitis. Pancreas, 40 (8), 1241-1244.
• Chen X, Wu Y, Liu L, Su Y, Peng Y, Jiang L, Liu X, Huang D, 2010: Relationship between high density lipoprotein antioxidant activity and carotid arterial intima-media thickness in patients with essential hypertension. Clin Exp Hypertens, 32 (1), 13-20.
• Clemens DL, Mahan KJ, 2010: Alcoholic pancreatitis: Lessons from the liver. World J Gastroenterol: WJG, 16 (11), 1314-1320.
• Crockett SD, Wani S, Gardner TB, Falck-Ytter Y, Barkun AN, 2018: American Gastroenterological Association Institute Clinical Guidelines Committee. American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis. Gastroenterology, 154 (4), 1096-1101. doi: 10.1053/j.gastro.2018.01.032.
• Czakó L, Takács T, Varga IS, Tiszlavicz L, Hegyi P, Matkovics B, Lonovics J, 2000: Oxidative stress in distant organs and the effects of allopurinol during experimental acute pancreatitis. Int J Pancreatol, 27 (3), 209-216.
• Darakhshan S, Pour AB, Colagar AH, Sisakhtnezhad S, 2015: Thymoquinone and its therapeutic potentials. Pharmacol Res, 95, 138-158.
• Dominguez-Munoz J, Malfertheiner P, Ditschuneit H, Blanco-Chavez J, UhL W, Bückler M, Ditschuneit H, 1991: Hyperlipidemia in acute pancreatitis. Int J Pancreatol, 10 (3), 261-267.
• Dziurkowska-Marek A, Marek TA, Nowak A, Kacperek-Hartleb T, Sierka E, Nowakowska-Dulawa E, 2004: The dynamics of the oxidant-antioxidant balance in the early phase of human acute biliary pancreatitis. Pancreatology, 4 (3-4), 215-222.
• El-Dakhakhny M, Mady NI, Halim MA, 2000: Nigella sativa L. oil protects against induced hepatotoxicity and improves serum lipid profile in rats. Arzneimittelforschung, 50 (9), 832-836.
• Emancipator K, Csako G, Elin R, 1992: In vitro inactivation of bacterial endotoxin by human lipoproteins and apolipoproteins. Infect Immun, 60 (2), 596-601.
• Ettinger WH, Varma VK, Sorci-Thomas M, Parks JS, Sigmon RC, Smith TK, Verdery RB, 1994: Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells. Arterioscler Thromb Vasc Biol, 14 (1), 8-13.
• Farzaneh E, Nia FR, Mehrtash M, Mirmoeini FS, Jalilvand M, 2014: The effects of 8-week Nigella sativa supplementation and aerobic training on lipid profile and VO2 max in sedentary overweight females. Int J Prev Med, 5 (2), 210.
• Flegel W, Baumstark M, Weinstock C, Berg A, Northoff H, 1993: Prevention of endotoxin-induced monokine release by human low-and high-density lipoproteins and by apolipoprotein AI. Infect Immun, 61 (12), 5140-5146.
• Fouad A, Jresat I, 2015: Thymoquinone therapy abrogates toxic effect of cadmium on rat testes. Andrologia, 47 (4), 417-426.
• Gholamnezhad Z, Havakhah S, Boskabady MH, 2016: Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. J Ethnopharmacol, 190, 372-386.
• Güllü EB, Gülcan A, 2013: Timokinon: Nigella Sativa’nın biyoaktif komponenti. Kocatepe Vet Derg, 6 (1), 51-61.
• Ibrahim RM, Hamdan NS, Mahmud R, Imam MU, Saini SM, Abd Rashid SN, Abd Ghafar SA, Ab Latiff L, Ismail M, 2014: A randomised controlled trial on hypolipidemic effects of Nigella Sativa seeds powder in menopausal women. J Transl Med, 12 (1), 1-7.
• Ikeı S, Ogawa M, Yamaguchı Y, 1998: Blood concentrations of polymorphonuclear leucocyte elastase and interleukin‐6 are indicators for the occurrence of multiple organ failures at the early stage of acute pancreatitis. J Gastroenterol Hepatol, 13 (12), 1274-1283.
• Ismail OZ, Bhayana V, 2017: Lipase or amylase for the diagnosis of acute pancreatitis? Clin Biochem, 50 (18), 1275-1280.
• Kocyigit Y, Atamer Y, Uysal E, 2009: The effect of dietary supplementation of Nigella sativa L. on serum lipid profile in rats. Saudi Med J, 30 (7), 893-896.
• Kumar MM, Tamizhselvi R, 2020: Protective effect of diallyl disulfide against cerulein-induced acute pancreatitis and associated lung injury in mice. Int Immunopharmacol, 80, 106136. doi: 10.1016/j.intimp.2019.106136.
• Lam PP, Cosen Binker LI, Lugea A, Pandol SJ, Gaisano HY, 2007: Alcohol redirects CCK‐mediated apical exocytosis to the acinar basolateral membrane in alcoholic pancreatitis. Traffic, 8 (5), 605-617.
• Lee JH, Park JH, Lee SH, Kim JR, Cho KH, 2010: Elevated HDL2-paraoxonase and reduced CETP activity are associated with a dramatically lower ratio of LDL-cholesterol/total cholesterol in a hypercholesterolemic and hypertriglyceridemic patient. Int J Mol Med, 25 (6), 945-951.
• Leema G, Tamizhselvi R, 2018: Protective Effect of Scopoletin Against Cerulein-Induced Acute Pancreatitis and Associated Lung Injury in Mice. Pancreas, 47 (5), 577-585. doi: 10.1097/MPA.0000000000001034.
• Leung PS, Chan YC, 2009: Role of oxidative stress in pancreatic inflammation. Antioxid Redox Sign, 11 (1), 135-166.
• Liao W, Rudling M, Angelin B, 1999: Endotoxin suppresses mouse hepatic low‐density lipoprotein–receptor expression via a pathway independent of the toll‐like receptor 4. Hepatology, 30 (5), 1252-1256.
• Nader MA, El-Agamy DS, Suddek GM, 2010: Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits. Arch Pharm Res, 33 (4), 637-643.
• Nagi MN, Almakki HA, Sayed-Ahmed MM, Al-Bekairi AM, 2010: Thymoquinone supplementation reverses acetaminophen-induced oxidative stress, nitric oxide production and energy decline in mice liver. Food Chem Toxicol, 48 (8-9), 2361-2365. doi: 10.1016/j.fct.2010.05.072.
• Najmi A, Nasiruddin M, Khan R, Haque SF, 2012: Therapeutic effect of Nigella sativa in patients of poor glycemic control. Asian J Pharm Clin Res, 5 (3), 224-228.
• Najmi A, Nasiruddin M, Khan RA, Haque SF, 2008: Effect of Nigella sativa oil on various clinical and biochemical parameters of insulin resistance syndrome. Int J Diabetes Dev Ctries, 28 (1), 11-14.
• Negi N, Mokta J, Sharma B, Sharma R, Jhobta A, Bodh V, Ranjan A, 2018: Clinical Profile and Outcome of Acute Pancreatitis: A Hospital-Based Prospective Observational Study in Subhimalayan State. J Assoc Phys India, 66, 22-24.
• Nonaka A, Manabe T, Kyogoku T, Tamura K, Tobe T, 1990: Changes in lipid peroxide and oxygen radical scavengers in cerulein-induced acute pancreatitis. Digestion, 47 (3), 130-137.
• Nonaka A, Manabe T, Tamura K, Asano N, Imanishi K, Tobe T, 1989: Changes of xanthine oxidase, lipid peroxide and superoxide dismutase in mouse acute pancreatitis. Digestion, 43 (1-2), 41-46.
• Okura Y, Hayashi K, Shingu T, Kajiyama G, Nakashima Y, Saku K, 2004: Diagnostic evaluation of acute pancreatitis in two patients with hypertriglyceridemia. World J Gastroenterol: WJG, 10 (24), 3691.
• Pădureanu V, Florescu DN, Padureanu R, Ghenea AE, Gheonea DI, Oancea CN, 2022: Role of antioxidants and oxidative stress in the evolution of acute pancreatitis (Review). Exp Ther Med, 23. doi: 10.3892/etm.2022.11120.
• Pakala R, Stabile E, Jang GJ, Clavijo L, Waksman R, 2005: Rapamycin attenuates atherosclerotic plaque progression in apolipoprotein E knockout mice: inhibitory effect on monocyte chemotaxis. J Cardiovasc Pharmacol, 46 (4), 481-486.
• Patel K, Trivedi RN, Durgampudi C, Noel P, Cline RA, DeLany JP, Navina S, Singh VP, 2015: Lipolysis of visceral adipocyte triglyceride by pancreatic lipases converts mild acute pancreatitis to severe pancreatitis independent of necrosis and inflammation. Am J Pathol, 185 (3), 808-819.
• Peng YS, Chen YC, Tian YC, Yang CW, Lien JM, Fang JT, Wu CS, Hung CF, Hwang TL, Tsai YH, 2015: Serum levels of apolipoprotein AI and high-density lipoprotein can predict organ failure in acute pancreatitis. Crit Care, 19 (1), 1-9.
• Podrez EA, 2010: Anti‐oxidant properties of high‐density lipoprotein and atherosclerosis. Clin Exp Pharmacol Physiol, 37 (7), 719-725.
• Qidwai W, Ashfaq T, 2014: Effect of dietary supplementation of black seed (N. Sativa L.) on lipid profile of patients suffering from diabetes. Antiinflamm Antiallergy Agents Med Chem, 13 (1), 3-8. doi: 10.2174/18715230113129990020.
• Que RS, Cao LP, Ding GP, Hu JA, Mao KJ, Wang GF, 2010: Correlation of nitric oxide and other free radicals with the severity of acute pancreatitis and complicated systemic inflammatory response syndrome. Pancreas, 39 (4), 536-540. doi: 10.1097/MPA.0b013e3181c0e199.
• Radad K, Moldzio R, Taha M, Rausch WD, 2009: Thymoquinone protects dopaminergic neurons against MPP+ and rotenone. Phytother Res, 23 (5), 696-700. doi: 10.1002/ptr.2708.
• Ragheb A, Elbarbry F, Prasad K, Mohamed A, Ahmed MS, Shoker A, 2008: Attenuation of the development of hypercholesterolemic atherosclerosis by thymoquinone. Int J Angiol, 17 (4), 186-192. doi: 10.1055/s-0031-1278307.
• Roberts SE, Morrison-Rees S, John A, Williams JG, Brown TH, Samuel DG, 2017: The incidence and aetiology of acute pancreatitis across Europe. Pancreatology, 17(2), 155-165.
• Sabzghabaee AM, Dianatkhah M, Sarrafzadegan N, Asgary S, Ghannadi A, 2012: Clinical evaluation of Nigella sativa seeds for the treatment of hyperlipidemia: a randomized, placebo controlled clinical trial. Med Arch, 66 (3), 198-200.
• Schmidt J, Lewandrowski K, Fernandez-del Castillo C, Mandavilli U, Compton C, Warshaw A, Rattner D, 1992: Histopathologic correlates of serum amylase activity in acute experimental pancreatitis. Dig Dis Sci, 37 (9), 1426-1433.
• Schoenberg MH, Birk D, Beger HG, 1995: Oxidative stress in acute and chronic pancreatitis. Am J Clin Nutr, 62 (6 Suppl), 1306S-1314S. doi: 10.1093/ajcn/62.6.1306S.
• Shabana A, El-Menyar A, Asim M, Al-Azzeh H, Al Thani H, 2013: Cardiovascular benefits of black cumin (Nigella sativa). Cardiovasc Toxicol, 13 (1), 9-21.
• Song R, Yu D, Park J, 2016: Changes in gene expression of tumor necrosis factor alpha and interleukin 6 in a canine model of caerulein-induced pancreatitis. Can J Vet Res, 80 (3), 236-241.
• Sweiry JH, Mann GE, 1996: Role of oxidative stress in the pathogenesis of acute pancreatitis. Scand J Gastroenterol, 219, 10‑15. doi: 10.3109/00365529609104992.
• Tribble DL, Chu BM, Gong EL, van Venrooij F, Nichols A, 1995: HDL antioxidant effects as assessed using a nonexchangeable probe to monitor particle-specific peroxidative stress in LDL-HDL mixtures. J Lipid Res, 36 (12), 2580-2589.
• Tsai K, Wang S, Chen T, Kong CW, Chang FY, Lee SD, Lu FJ, 1998: Oxidative stress: an important phenomenon with pathogenetic significance in the progression of acute pancreatitis. Gut, 42 (6), 850-855.
• Tvarijonaviciute A, García-Martínez JD, Caldin M, Martínez-Subiela S, Tecles F, Pastor J, Ceron JJ, 2015: Serum paraoxonase 1 (PON1) activity in acute pancreatitis of dogs. J Small Anim Pract, 56 (1), 67-71. doi: 10.1111/jsap.12297.
• Unal E, Uzun H, Kusaslan R, Dogan M, Genc H, Gunes P, Titiz I, 2005: Serum paraoxonase (a high-density lipoprotein-associated lipophilic antioxidant) activity and lipid profile in experimental acute pancreatitis. Pancreas, 31 (1), 84-87.
• Van DIjk SM, Hallensleben NDL, van Santvoort HC, Fockens P, van Goor H, Bruno MJ, Besselink MG, ; Dutch Pancreatitis Study Group, 2017: Acute pancreatitis: recent advances through randomised trials. Gut, 66 (11), 2024-2032. doi: 10.1136/gutjnl-2016-313595.
• Vardar D, Mollahaliloğlu S, Öztaş D, 2018: Examining the effects of phytochemicals used in phytotherapy on public health. J Health Sci Med, 1 (4), 99-105.
• Velusamy RK, Tamizhselvi R, 2018: Protective effect of methylsulfonylmethane in caerulein-induced acute pancreatitis and associated lung injury in mice. J Pharm Pharmacol, 70 (9), 1188-1199. doi: 10.1111/jphp.12946.
• Wan J, He W, Zhu Y, Zhu Y, Zeng H, Liu P, Xia L, Lu N, 2017: Stratified analysis and clinical significance of elevated serum triglyceride levels in early acute pancreatitis: a retrospective study. Lipids Health Dis, 16 (1), 1-7.
• Wang GJ, Gao CF, Wei D, Wang C, Ding SQ, 2009a: Acute pancreatitis: etiology and common pathogenesis. World J Gastroenterol: WJG, 15 (12), 1427-1430.
• Wang YJ, Sun JB, Li F, Zhang SW, 2006: Hyperlipidemia intensifies cerulein-induced acute pancreatitis associated with activation of protein kinase C in rats. World J Gastroenterol: WJG, 12 (18), 2908-2913.
• Wang Y, Sternfeld L, Yang F, Rodriguez JA, Ross C, Hayden MR, Carriere F, Liu G, Hofer W, Schulz I, 2009b: Enhanced susceptibility to pancreatitis in severe hypertriglyceridaemic lipoprotein lipase-deficient mice and agonist-like function of pancreatic lipase in pancreatic cells. Gut, 58 (3), 422-430.
• Weidner G, Connor SL, Chesney MA, Burns JW, Connor WE, Matarazzo JD, Mendell NR, 1991: Sex differences in high density lipoprotein cholesterol among low-level alcohol consumers. Circulation, 83 (1), 176-180.
• Werlang ME, Lewis MD, Bartel MJ, 2017: Tumor Necrosis Factor Alpha Inhibitor-Induced Acute Pancreatitis. ACG Case Rep J, 4 (1), e103. doi: 10.14309/crj.2017.103.
• Woo CC, Kumar AP, Sethi G, Tan KHB, 2012: Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol, 83 (4), 443-451.
• Yvan-Charvet L, Kling J, Pagler T, Li H, Hubbard B, Fisher T, Sparrow CP, Taggart AK, Tall AR, 2010: Cholesterol efflux potential and antiinflammatory properties of high-density lipoprotein after treatment with niacin or anacetrapib. Arterioscler Thromb Vasc Biol, 30 (7), 1430-1438.
• Zaoui A, Cherrah Y, Alaoui K, Mahassine N, Amarouch H, Hassar M, 2002: Effects of Nigella sativa fixed oil on blood homeostasis in rat. J Ethnopharmacol, 79 (1), 23-26.
• Zechner R, Kienesberger PC, Haemmerle G, Zimmermann R, Lass A, 2009: Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J Lipid Res, 50 (1), 3-21.
• Zhang X, Zhu C, Wu D, Jiang X, 2010: Possible role of toll-like receptor 4 in acute pancreatitis. Pancreas, 39 (6), 819-824.