Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2022

Open Access 01-12-2022 | Acute Pancreatitis | Research

Genistein attenuated oxidative stress, inflammation, and apoptosis in L-arginine induced acute pancreatitis in mice

Authors: Prasong Siriviriyakul, Jumlongluk Sriko, Kanjana Somanawat, Maneerat Chayanupatkul, Naruemon Klaikeaw, Duangporn Werawatganon

Published in: BMC Complementary Medicine and Therapies | Issue 1/2022

Login to get access

Abstract

Aim

Acute pancreatitis is a common and potentially serious condition. However, a specific treatment for this condition is still lacking. Genistein, with its anti-oxidant and anti-inflammatory effects, could possibly be used to tackle the underlying pathophysiology of acute pancreatitis. Therefore, the aim of this study was to investigate the effects of genistein on oxidative stress, inflammation, and apoptosis in acute pancreatitis induced by L-arginine in mice.

Methods

Twenty-four male ICR mice were equally divided into 4 groups: Control (Con); Acute pancreatitis (AP) group: Two doses of i.p. 350 mg/100 g body weight (BW) of L-arginine were administered 1 h apart; AP and low-dose genistein (LG) group: mice were given i.p. injection of 10 mg/kg genistein 2 h prior to L-arginine injection followed by once-daily dosing for 3 days; and AP and high-dose genistein (HG) group: mice were given 100 mg/kg genistein with the similar protocol as the LG group. Pancreatic tissue was evaluated for histopathological changes and acinar cell apoptosis, malondialdehyde (MDA) levels, immunohistochemical staining for myeloperoxidase (MPO), nuclear factor-kappa beta (NF-kB), and 4-hydroxynonenal (4-HNE). Serum levels of amylase (AMY), c-reactive protein (CRP), and interleukin (IL)-6 were measured.

Results

Significant increases in the degree of acinar cell apoptosis, pancreatic MDA, serum IL-6 and amylase, MPO, NF-kB and 4-HNE positivity were observed in the AP group. All these parameters declined after low- and high-dose genistein treatment. Severe pancreatic inflammation, edema, and acinar cell necrosis were observed in the AP group. Significant improvement of histopathological changes was seen in both low- and high-dose genistein groups. There were no significant differences in any parameters between low and high doses of genistein.

Conclusion

Genistein could attenuate the severity of histopathological changes in acute pancreatitis through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.
Appendix
Available only for authorised users
Literature
1.
go back to reference Wilson C, McArdle C, Carter D, Imrie C. Surgical treatment of acute necrotizing pancreatitis. Br J Surg. 1988;75:1119–23.PubMedCrossRef Wilson C, McArdle C, Carter D, Imrie C. Surgical treatment of acute necrotizing pancreatitis. Br J Surg. 1988;75:1119–23.PubMedCrossRef
2.
go back to reference Hofbauer B, Saluja AK, Lerch MM, Bhagat L, Bhatia M, Lee HS, et al. Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats. Am J Physiol. 1998;275(2):G352-362.PubMedCrossRef Hofbauer B, Saluja AK, Lerch MM, Bhagat L, Bhatia M, Lee HS, et al. Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats. Am J Physiol. 1998;275(2):G352-362.PubMedCrossRef
3.
go back to reference Frossard JL. Trypsin activation peptide (TAP) in acute pancreatitis: from pathophysiology to clinical usefulness. Jop. 2001;2(2):69–77.PubMed Frossard JL. Trypsin activation peptide (TAP) in acute pancreatitis: from pathophysiology to clinical usefulness. Jop. 2001;2(2):69–77.PubMed
4.
go back to reference Schneider L, Büchler MW, Werner J. Acute pancreatitis with an emphasis on infection. Infect Dis Clin North Am. 2010;24(4):921–41 (viii).PubMedCrossRef Schneider L, Büchler MW, Werner J. Acute pancreatitis with an emphasis on infection. Infect Dis Clin North Am. 2010;24(4):921–41 (viii).PubMedCrossRef
5.
go back to reference Gross V, Leser HG, Heinisch A, Schölmerich J. Inflammatory mediators and cytokines–new aspects of the pathophysiology and assessment of severity of acute pancreatitis? Hepatogastroenterology. 1993;40(6):522–30.PubMed Gross V, Leser HG, Heinisch A, Schölmerich J. Inflammatory mediators and cytokines–new aspects of the pathophysiology and assessment of severity of acute pancreatitis? Hepatogastroenterology. 1993;40(6):522–30.PubMed
7.
go back to reference Ruiz-Larrea B, Leal A, Martín C, Martínez R, Lacort M. Effects of estrogens on the redox chemistry of iron: a possible mechanism of the antioxidant action of estrogens. Steroids. 1995;60(11):780–3.PubMedCrossRef Ruiz-Larrea B, Leal A, Martín C, Martínez R, Lacort M. Effects of estrogens on the redox chemistry of iron: a possible mechanism of the antioxidant action of estrogens. Steroids. 1995;60(11):780–3.PubMedCrossRef
8.
go back to reference Arora A, Nair MG, Strasburg GM. Antioxidant activities of isoflavones and their biological metabolites in a liposomal system. Arch Biochem Biophys. 1998;356(2):133–41.PubMedCrossRef Arora A, Nair MG, Strasburg GM. Antioxidant activities of isoflavones and their biological metabolites in a liposomal system. Arch Biochem Biophys. 1998;356(2):133–41.PubMedCrossRef
9.
go back to reference Wei H, Bowen R, Cai Q, Barnes S, Wang Y. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med. 1995;208(1):124–30.PubMedCrossRef Wei H, Bowen R, Cai Q, Barnes S, Wang Y. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med. 1995;208(1):124–30.PubMedCrossRef
10.
go back to reference Gupta SK, Dongare S, Mathur R, Mohanty IR, Srivastava S, Mathur S, et al. Genistein ameliorates cardiac inflammation and oxidative stress in streptozotocin-induced diabetic cardiomyopathy in rats. Mol Cell Biochem. 2015;408(1–2):63–72.PubMedCrossRef Gupta SK, Dongare S, Mathur R, Mohanty IR, Srivastava S, Mathur S, et al. Genistein ameliorates cardiac inflammation and oxidative stress in streptozotocin-induced diabetic cardiomyopathy in rats. Mol Cell Biochem. 2015;408(1–2):63–72.PubMedCrossRef
11.
go back to reference Chang T, Neelakandan C, DeFine L, Alexander T, Kyu T. Effects of glucose on cell viability and antioxidant and anti-inflammatory properties of phytochemicals and phytochemically modified membranes. J Phys Chem B. 2014;118(41):11993–2001.PubMedCrossRef Chang T, Neelakandan C, DeFine L, Alexander T, Kyu T. Effects of glucose on cell viability and antioxidant and anti-inflammatory properties of phytochemicals and phytochemically modified membranes. J Phys Chem B. 2014;118(41):11993–2001.PubMedCrossRef
12.
go back to reference Ji G, Zhang Y, Yang Q, Cheng S, Hao J, Zhao X, et al. Genistein suppresses LPS-induced inflammatory response through inhibiting NF-κB following AMP kinase activation in RAW 264.7 macrophages. PLoS One. 2012;7(12):e53101.PubMedPubMedCentralCrossRef Ji G, Zhang Y, Yang Q, Cheng S, Hao J, Zhao X, et al. Genistein suppresses LPS-induced inflammatory response through inhibiting NF-κB following AMP kinase activation in RAW 264.7 macrophages. PLoS One. 2012;7(12):e53101.PubMedPubMedCentralCrossRef
13.
go back to reference Siriviriyakul P, Chingchit T, Klaikeaw N, Chayanupatkul M, Werawatganon D. Effects of curcumin on oxidative stress, inflammation and apoptosis in L-arginine induced acute pancreatitis in mice. Heliyon. 2019;5(8):e02222–e02222.PubMedPubMedCentralCrossRef Siriviriyakul P, Chingchit T, Klaikeaw N, Chayanupatkul M, Werawatganon D. Effects of curcumin on oxidative stress, inflammation and apoptosis in L-arginine induced acute pancreatitis in mice. Heliyon. 2019;5(8):e02222–e02222.PubMedPubMedCentralCrossRef
14.
go back to reference Susutlertpanya W, Werawatganon D, Siriviriyakul P, Klaikeaw N. Genistein Attenuates Nonalcoholic Steatohepatitis and Increases Hepatic PPARγ in a Rat Model. Evid Based Complement Alternat Med. 2015;2015:509057–509057.PubMedPubMedCentralCrossRef Susutlertpanya W, Werawatganon D, Siriviriyakul P, Klaikeaw N. Genistein Attenuates Nonalcoholic Steatohepatitis and Increases Hepatic PPARγ in a Rat Model. Evid Based Complement Alternat Med. 2015;2015:509057–509057.PubMedPubMedCentralCrossRef
15.
go back to reference De Cock HE, Forman MA, Farver TB, Marks SL. Prevalence and histopathologic characteristics of pancreatitis in cats. Vet Pathol. 2007;44(1):39–49.PubMedCrossRef De Cock HE, Forman MA, Farver TB, Marks SL. Prevalence and histopathologic characteristics of pancreatitis in cats. Vet Pathol. 2007;44(1):39–49.PubMedCrossRef
16.
go back to reference Kapiotis S, Hermann M, Held I, Seelos C, Ehringer H, Gmeiner BM. Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL. Arterioscler Thromb Vasc Biol. 1997;17(11):2868–74.PubMedCrossRef Kapiotis S, Hermann M, Held I, Seelos C, Ehringer H, Gmeiner BM. Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL. Arterioscler Thromb Vasc Biol. 1997;17(11):2868–74.PubMedCrossRef
17.
go back to reference Jeong JW, Lee HH, Han MH, Kim GY, Kim WJ, Choi YH. Anti-inflammatory effects of genistein via suppression of the toll-like receptor 4-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglia. Chem Biol Interact. 2014;212:30–9.PubMedCrossRef Jeong JW, Lee HH, Han MH, Kim GY, Kim WJ, Choi YH. Anti-inflammatory effects of genistein via suppression of the toll-like receptor 4-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglia. Chem Biol Interact. 2014;212:30–9.PubMedCrossRef
18.
go back to reference Liang YC, Huang YT, Tsai SH, Lin-Shiau SY, Chen CF, Lin JK. Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis. 1999;20(10):1945–52.PubMedCrossRef Liang YC, Huang YT, Tsai SH, Lin-Shiau SY, Chen CF, Lin JK. Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis. 1999;20(10):1945–52.PubMedCrossRef
19.
go back to reference Ji G, Yang Q, Hao J, Guo L, Chen X, Hu J, et al. Anti-inflammatory effect of genistein on non-alcoholic steatohepatitis rats induced by high fat diet and its potential mechanisms. Int Immunopharmacol. 2011;11(6):762–8.PubMedCrossRef Ji G, Yang Q, Hao J, Guo L, Chen X, Hu J, et al. Anti-inflammatory effect of genistein on non-alcoholic steatohepatitis rats induced by high fat diet and its potential mechanisms. Int Immunopharmacol. 2011;11(6):762–8.PubMedCrossRef
20.
go back to reference Dan HL, Zhang YL, Zhang Y, Wang YD, Lai ZS, Yang YJ, et al. A novel method for preparation of tissue microarray. World J Gastroenterol. 2004;10(4):579–82.PubMedPubMedCentralCrossRef Dan HL, Zhang YL, Zhang Y, Wang YD, Lai ZS, Yang YJ, et al. A novel method for preparation of tissue microarray. World J Gastroenterol. 2004;10(4):579–82.PubMedPubMedCentralCrossRef
21.
go back to reference Zhang XP, Zhang L, Xu HM, Xu YP, Cheng QH, Wang JM, et al. Application of tissue microarrays to study the influence of dexamethasone on NF-kappaB expression of pancreas in rat with severe acute pancreatitis. Dig Dis Sci. 2008;53(2):571–80.PubMedCrossRef Zhang XP, Zhang L, Xu HM, Xu YP, Cheng QH, Wang JM, et al. Application of tissue microarrays to study the influence of dexamethasone on NF-kappaB expression of pancreas in rat with severe acute pancreatitis. Dig Dis Sci. 2008;53(2):571–80.PubMedCrossRef
22.
go back to reference Cregger M, Berger AJ, Rimm DL. Immunohistochemistry and quantitative analysis of protein expression. Arch Pathol Lab Med. 2006;130(7):1026–30.PubMedCrossRef Cregger M, Berger AJ, Rimm DL. Immunohistochemistry and quantitative analysis of protein expression. Arch Pathol Lab Med. 2006;130(7):1026–30.PubMedCrossRef
23.
go back to reference Sung MJ, Kim DH, Jung YJ, Kang KP, Lee AS, Lee S, et al. Genistein protects the kidney from cisplatin-induced injury. Kidney Int. 2008;74(12):1538–47.PubMedCrossRef Sung MJ, Kim DH, Jung YJ, Kang KP, Lee AS, Lee S, et al. Genistein protects the kidney from cisplatin-induced injury. Kidney Int. 2008;74(12):1538–47.PubMedCrossRef
24.
go back to reference Dawra R, Sharif R, Phillips P, Dudeja V, Dhaulakhandi D, Saluja AK. Development of a new mouse model of acute pancreatitis induced by administration of L-arginine. Am J Physiol Gastrointest Liver Physiol. 2007;292(4):G1009-1018.PubMedCrossRef Dawra R, Sharif R, Phillips P, Dudeja V, Dhaulakhandi D, Saluja AK. Development of a new mouse model of acute pancreatitis induced by administration of L-arginine. Am J Physiol Gastrointest Liver Physiol. 2007;292(4):G1009-1018.PubMedCrossRef
25.
go back to reference Malleo G, Mazzon E, Siriwardena AK, Cuzzocrea S. Role of tumor necrosis factor-alpha in acute pancreatitis: from biological basis to clinical evidence. Shock. 2007;28(2):130–40.PubMedCrossRef Malleo G, Mazzon E, Siriwardena AK, Cuzzocrea S. Role of tumor necrosis factor-alpha in acute pancreatitis: from biological basis to clinical evidence. Shock. 2007;28(2):130–40.PubMedCrossRef
26.
go back to reference Szabolcs A, Reiter RJ, Letoha T, Hegyi P, Papai G, Varga I, et al. Effect of melatonin on the severity of L-arginine-induced experimental acute pancreatitis in rats. World J Gastroenterol. 2006;12(2):251–8.PubMedPubMedCentralCrossRef Szabolcs A, Reiter RJ, Letoha T, Hegyi P, Papai G, Varga I, et al. Effect of melatonin on the severity of L-arginine-induced experimental acute pancreatitis in rats. World J Gastroenterol. 2006;12(2):251–8.PubMedPubMedCentralCrossRef
28.
go back to reference Sidhapuriwala JN, Hegde A, Ang AD, Zhu YZ, Bhatia M. Effects of S-propargyl-cysteine (SPRC) in caerulein-induced acute pancreatitis in mice. PLoS ONE. 2012;7(3): e32574.PubMedPubMedCentralCrossRef Sidhapuriwala JN, Hegde A, Ang AD, Zhu YZ, Bhatia M. Effects of S-propargyl-cysteine (SPRC) in caerulein-induced acute pancreatitis in mice. PLoS ONE. 2012;7(3): e32574.PubMedPubMedCentralCrossRef
29.
go back to reference Yenicerioglu A, Cetinkaya Z, Girgin M, Ustundag B, Ozercan IH, Ayten R, et al. Effects of trimetazidine in acute pancreatitis induced by L-arginine. Can J Surg. 2013;56(3):175–9.PubMedPubMedCentralCrossRef Yenicerioglu A, Cetinkaya Z, Girgin M, Ustundag B, Ozercan IH, Ayten R, et al. Effects of trimetazidine in acute pancreatitis induced by L-arginine. Can J Surg. 2013;56(3):175–9.PubMedPubMedCentralCrossRef
31.
go back to reference Kim DH, Jung WS, Kim ME, Lee HW, Youn HY, Seon JK, et al. Genistein inhibits pro-inflammatory cytokines in human mast cell activation through the inhibition of the ERK pathway. Int J Mol Med. 2014;34(6):1669–74.PubMedCrossRef Kim DH, Jung WS, Kim ME, Lee HW, Youn HY, Seon JK, et al. Genistein inhibits pro-inflammatory cytokines in human mast cell activation through the inhibition of the ERK pathway. Int J Mol Med. 2014;34(6):1669–74.PubMedCrossRef
32.
go back to reference Leung PS, Chan YC. Role of oxidative stress in pancreatic inflammation. Antioxid Redox Signal. 2009;11(1):135–65.PubMedCrossRef Leung PS, Chan YC. Role of oxidative stress in pancreatic inflammation. Antioxid Redox Signal. 2009;11(1):135–65.PubMedCrossRef
33.
go back to reference Li X, Xu T, Lian Q, Zeng B, Zhang B, Xie Y. Protective effect of genistein on lipopolysaccharide-induced acute lung injury in rats. J Huazhong Univ Sci Technolog Med Sci. 2005;25(4):454–7.PubMedCrossRef Li X, Xu T, Lian Q, Zeng B, Zhang B, Xie Y. Protective effect of genistein on lipopolysaccharide-induced acute lung injury in rats. J Huazhong Univ Sci Technolog Med Sci. 2005;25(4):454–7.PubMedCrossRef
34.
go back to reference Kang JL, Lee HW, Lee HS, Pack IS, Chong Y, Castranova V, et al. Genistein prevents nuclear factor-kappa B activation and acute lung injury induced by lipopolysaccharide. Am J Respir Crit Care Med. 2001;164(12):2206–12.PubMedCrossRef Kang JL, Lee HW, Lee HS, Pack IS, Chong Y, Castranova V, et al. Genistein prevents nuclear factor-kappa B activation and acute lung injury induced by lipopolysaccharide. Am J Respir Crit Care Med. 2001;164(12):2206–12.PubMedCrossRef
35.
go back to reference Czakó L, Takács T, Varga IS, Tiszlavicz L, Hai DQ, Hegyi P, et al. Involvement of oxygen-derived free radicals in L-arginine-induced acute pancreatitis. Dig Dis Sci. 1998;43(8):1770–7.PubMedCrossRef Czakó L, Takács T, Varga IS, Tiszlavicz L, Hai DQ, Hegyi P, et al. Involvement of oxygen-derived free radicals in L-arginine-induced acute pancreatitis. Dig Dis Sci. 1998;43(8):1770–7.PubMedCrossRef
36.
go back to reference Tiruveedi VL, Bale S, Khurana A, Godugu C. Withaferin A, a novel compound of Indian ginseng (Withania somnifera), ameliorates Cerulein-induced acute pancreatitis: Possible role of oxidative stress and inflammation. Phytother Res. 2018;32(12):2586–96.PubMedCrossRef Tiruveedi VL, Bale S, Khurana A, Godugu C. Withaferin A, a novel compound of Indian ginseng (Withania somnifera), ameliorates Cerulein-induced acute pancreatitis: Possible role of oxidative stress and inflammation. Phytother Res. 2018;32(12):2586–96.PubMedCrossRef
37.
go back to reference Robles L, Vaziri ND, Ichii H. Role of oxidative stress in the pathogenesis of pancreatitis: effect of antioxidant therapy. Pancreat Disord Ther. 2013;3(1):112.PubMedPubMedCentralCrossRef Robles L, Vaziri ND, Ichii H. Role of oxidative stress in the pathogenesis of pancreatitis: effect of antioxidant therapy. Pancreat Disord Ther. 2013;3(1):112.PubMedPubMedCentralCrossRef
38.
go back to reference Shi C, Andersson R, Zhao X, Wang X. Potential role of reactive oxygen species in pancreatitis-associated multiple organ dysfunction. Pancreatology. 2005;5(4–5):492–500.PubMedCrossRef Shi C, Andersson R, Zhao X, Wang X. Potential role of reactive oxygen species in pancreatitis-associated multiple organ dysfunction. Pancreatology. 2005;5(4–5):492–500.PubMedCrossRef
39.
go back to reference Jakkampudi A, Jangala R, Reddy BR, Mitnala S, Nageshwar Reddy D, Talukdar R. NF-κB in acute pancreatitis: Mechanisms and therapeutic potential. Pancreatology. 2016;16(4):477–88.PubMedCrossRef Jakkampudi A, Jangala R, Reddy BR, Mitnala S, Nageshwar Reddy D, Talukdar R. NF-κB in acute pancreatitis: Mechanisms and therapeutic potential. Pancreatology. 2016;16(4):477–88.PubMedCrossRef
40.
go back to reference Huang H, Liu Y, Daniluk J, Gaiser S, Chu J, Wang H, et al. Activation of nuclear factor-κB in acinar cells increases the severity of pancreatitis in mice. Gastroenterology. 2013;144(1):202–10.PubMedCrossRef Huang H, Liu Y, Daniluk J, Gaiser S, Chu J, Wang H, et al. Activation of nuclear factor-κB in acinar cells increases the severity of pancreatitis in mice. Gastroenterology. 2013;144(1):202–10.PubMedCrossRef
41.
go back to reference Motoo Y, Taga K, Su SB, Xie MJ, Sawabu N. Arginine induces apoptosis and gene expression of pancreatitis-associated protein (PAP) in rat pancreatic acinar AR4-2J cells. Pancreas. 2000;20(1):61–6.PubMedCrossRef Motoo Y, Taga K, Su SB, Xie MJ, Sawabu N. Arginine induces apoptosis and gene expression of pancreatitis-associated protein (PAP) in rat pancreatic acinar AR4-2J cells. Pancreas. 2000;20(1):61–6.PubMedCrossRef
42.
go back to reference Awasthi YC, Sharma R, Sharma A, Yadav S, Singhal SS, Chaudhary P, et al. Self-regulatory role of 4-hydroxynonenal in signaling for stress-induced programmed cell death. Free Radic Biol Med. 2008;45(2):111–8.PubMedPubMedCentralCrossRef Awasthi YC, Sharma R, Sharma A, Yadav S, Singhal SS, Chaudhary P, et al. Self-regulatory role of 4-hydroxynonenal in signaling for stress-induced programmed cell death. Free Radic Biol Med. 2008;45(2):111–8.PubMedPubMedCentralCrossRef
43.
go back to reference Sayed N, Khurana A, Godugu C. Pharmaceutical perspective on the translational hurdles of phytoconstituents and strategies to overcome. J Drug Deliv Sci Technol. 2019;53:101201.CrossRef Sayed N, Khurana A, Godugu C. Pharmaceutical perspective on the translational hurdles of phytoconstituents and strategies to overcome. J Drug Deliv Sci Technol. 2019;53:101201.CrossRef
Metadata
Title
Genistein attenuated oxidative stress, inflammation, and apoptosis in L-arginine induced acute pancreatitis in mice
Authors
Prasong Siriviriyakul
Jumlongluk Sriko
Kanjana Somanawat
Maneerat Chayanupatkul
Naruemon Klaikeaw
Duangporn Werawatganon
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2022
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-022-03689-9

Other articles of this Issue 1/2022

BMC Complementary Medicine and Therapies 1/2022 Go to the issue