Hesperidin Inhibits High Mobility Group Protein B1 Releasing and Attenuates Acetaminophen-induced Hepatitis in Mice_West China Medical Journal

Authors：

 SHUKe-gang ¹ , CHENXiu-juan ¹ , LEIJiao ¹ , CHENMao-jian ¹ , NIEHao ² , ZHANGYan-xiang ² ,  WANGChao ² , GONGQuan ²

1. Clinical Medicine Major, School of Medicine, Yangtze University, Jingzhou, Hubei 434023, P. R. China;
2. Department of Pathogen Biology, School of Medicine, Yangtze University, Jingzhou, Hubei 434023, P. R. China;

Corresponding author：

WANGChao, Email: celful60@163.com

Keywords：

Hesperdin; Acetaminophen; Acute liver injury; High mobility group protein B1; Mice

DOI：

10.7507/1002-0179.20140262

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the protective effect of hesperdin (HDN) on acetaminophen (APAP)-induced acute liver injury in mice. Methods Forty-eight male BALB/c mice were randomly divided into six groups:normal group, model group, HDN (the doses respectively were 500, 250 and 125 mg/kg) group and bifendate group. The HDN group was separately intragastrically given different doses of hesperidin for ten days. The bifendate group was given bifendate. Acute liver injury was induced by injecting APAP (150 mg/kg) in all mice except those in the normal group. After 16 hours, all mice were sacrificed. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. The contents of glutathione (GSH) and malondialdehyde (MDA) in liver homogenates were determined. Pathological changes in hepatic tissue were observed under an optical microscope. The expression of high mobility group protein B1 (HMGB1) in hepatic tissue was measured by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Results HDN could significantly reduce serum ALT, AST, liver homogenate MDA levels, improve liver tissue GSH activity and the liver injury was lightened. By RT-PCR and immunohistochemistry, it showed that HDN could inhibit the releasing and expression of HMGB1. Conclusion HDN protects mice from acetaminophen-induced liver injury possibly via mechanisms related to inhibition of the expression and releasing of HMGB1.

Citation： SHUKe-gang, CHENXiu-juan, LEIJiao, CHENMao-jian, NIEHao, ZHANGYan-xiang, WANGChao, GONGQuan. Hesperidin Inhibits High Mobility Group Protein B1 Releasing and Attenuates Acetaminophen-induced Hepatitis in Mice. West China Medical Journal, 2014, 29(5): 858-862. doi: 10.7507/1002-0179.20140262 Copy

1.	Wilmsen PK, Spada DS, Salvador M. Antioxidant activity of the flavonoid hesperidin in chemical and biological systems[J]. J Agric Food Chem, 2005, 53(12):4757-4761.
2.	Kim JK, Sung NY, Srinivasan P, et al. Effect of gamma irradiated hyaluronic acid on acetaminophen induced acute hepatotoxicity[J]. Chem Biol Interact, 2008, 172(2):141-153.
3.	Choi EM, Kim YH. Hesperetin attenuates the highly reducing sugar-triggered inhibition of osteoblast differentiation[J]. Cell Biol Toxicol, 2008, 24(3):225-231.
4.	Morand C, Dubray C, Milenkovic D, et al. Hesperidin contributes to the vascular protective effects of orange juice:a randomized crossover study in healthy volunteers[J]. Am J Clin Nutr, 2011, 93(1):73-80.
5.	Aranganathan S, Selvam JP, Sangeetha N, et al. Modulatory efficacy of hesperetin (citrus flavanone) on xenobiotic-metabolizing enzymes during 1,2-dimethylhydrazine-induced colon carcinogenesis[J]. Chem Biol Interact, 2009, 180(2):254-261.
6.	Pradeep K, Ko KC, Choi MH, et al. Protective effect of hesperidin, a citrus flavanoglycone, against γ-radiation-induced tissue damage in Sprague-Dawley rats[J]. J Med Food, 2012, 15(5):419-427.
7.	Kumar P, Kumar A. Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington's like symptoms in rats:possible role of nitric oxide[J]. Behav Brain Res, 2010, 206(1):38-46.
8.	Goodwin GH, Sanders C, Johns EW. A new group of chromatin-associated proteins with a high content of acidic and basic amino acids[J]. Eur J Biochem, 1973, 38(1):14-19.
9.	Bell CW, Jiang W, Reich CF, et al. The extracellular release of HMGB1 during apoptotic cell death[J]. Am J Physiol Cell Physiol, 2006, 291(6):C1318-C1325.
10.	Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice[J]. Science, 1999, 285(5425):248-251.
11.	Ahmad ST, Arjumand W, Nafees S, et al. Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation[J]. Toxicol Lett, 2012, 208(2):149-161.
12.	Wang C, Nie H, Li K, et al. Curcumin inhibits HMGB1 releasing and attenuates concanavalin A-induced hepatitis in mice[J]. Eur J Pharmacol, 2012, 697(1/3):152-157.
13.	Shi Y, Sun J, He H, et al. Hepatoprotective effects of Ganoderma lucidum peptides against D-galactosamine-induced liver injury in mice[J]. J Ethnopharmacol, 2008, 117(3):415-419.
14.	Müller S, Ronfani L, Bianchi ME. Regulated expression and subcellular localization of HMGB1, a chromatin protein with a cytokine function[J]. J Intern Med, 2004, 255(3):332-343.
15.	Dumitriu IE, Baruah P, Manfredi AA, et al. HMGB1:guiding immunity from within[J]. Trends Immunol, 2005, 26(7):381-387.
16.	Watanabe T, Kubota S, Nagaya M, et al. The role of HMGB-1 on the development of necrosis during hepatic ischemia and hepatic ischemia/reperfusion injury in mice[J]. J Surg Res, 2005, 124(1):59-66.
17.	Wang H, Liao H, Ochani M, et al. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis[J]. Nat Med, 2004, 10(11):1216-1221.
18.	Tsung A, Sahai R, Tanaka H, et al. The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion[J]. J Exp Med, 2005, 201(7):1135-1143.
19.	Gong Q, Zhang H, Li JH, et al. High-mobility group box 1 exacerbates concanavalin A-induced hepatic injury in mice[J]. J Mol Med (Berl), 2010, 88(12):1289-1298.

1. Wilmsen PK, Spada DS, Salvador M. Antioxidant activity of the flavonoid hesperidin in chemical and biological systems[J]. J Agric Food Chem, 2005, 53(12):4757-4761.
2. Kim JK, Sung NY, Srinivasan P, et al. Effect of gamma irradiated hyaluronic acid on acetaminophen induced acute hepatotoxicity[J]. Chem Biol Interact, 2008, 172(2):141-153.
3. Choi EM, Kim YH. Hesperetin attenuates the highly reducing sugar-triggered inhibition of osteoblast differentiation[J]. Cell Biol Toxicol, 2008, 24(3):225-231.
4. Morand C, Dubray C, Milenkovic D, et al. Hesperidin contributes to the vascular protective effects of orange juice:a randomized crossover study in healthy volunteers[J]. Am J Clin Nutr, 2011, 93(1):73-80.
5. Aranganathan S, Selvam JP, Sangeetha N, et al. Modulatory efficacy of hesperetin (citrus flavanone) on xenobiotic-metabolizing enzymes during 1,2-dimethylhydrazine-induced colon carcinogenesis[J]. Chem Biol Interact, 2009, 180(2):254-261.
6. Pradeep K, Ko KC, Choi MH, et al. Protective effect of hesperidin, a citrus flavanoglycone, against γ-radiation-induced tissue damage in Sprague-Dawley rats[J]. J Med Food, 2012, 15(5):419-427.
7. Kumar P, Kumar A. Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington's like symptoms in rats:possible role of nitric oxide[J]. Behav Brain Res, 2010, 206(1):38-46.
8. Goodwin GH, Sanders C, Johns EW. A new group of chromatin-associated proteins with a high content of acidic and basic amino acids[J]. Eur J Biochem, 1973, 38(1):14-19.
9. Bell CW, Jiang W, Reich CF, et al. The extracellular release of HMGB1 during apoptotic cell death[J]. Am J Physiol Cell Physiol, 2006, 291(6):C1318-C1325.
10. Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice[J]. Science, 1999, 285(5425):248-251.
11. Ahmad ST, Arjumand W, Nafees S, et al. Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation[J]. Toxicol Lett, 2012, 208(2):149-161.
12. Wang C, Nie H, Li K, et al. Curcumin inhibits HMGB1 releasing and attenuates concanavalin A-induced hepatitis in mice[J]. Eur J Pharmacol, 2012, 697(1/3):152-157.
13. Shi Y, Sun J, He H, et al. Hepatoprotective effects of Ganoderma lucidum peptides against D-galactosamine-induced liver injury in mice[J]. J Ethnopharmacol, 2008, 117(3):415-419.
14. Müller S, Ronfani L, Bianchi ME. Regulated expression and subcellular localization of HMGB1, a chromatin protein with a cytokine function[J]. J Intern Med, 2004, 255(3):332-343.
15. Dumitriu IE, Baruah P, Manfredi AA, et al. HMGB1:guiding immunity from within[J]. Trends Immunol, 2005, 26(7):381-387.
16. Watanabe T, Kubota S, Nagaya M, et al. The role of HMGB-1 on the development of necrosis during hepatic ischemia and hepatic ischemia/reperfusion injury in mice[J]. J Surg Res, 2005, 124(1):59-66.
17. Wang H, Liao H, Ochani M, et al. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis[J]. Nat Med, 2004, 10(11):1216-1221.
18. Tsung A, Sahai R, Tanaka H, et al. The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion[J]. J Exp Med, 2005, 201(7):1135-1143.
19. Gong Q, Zhang H, Li JH, et al. High-mobility group box 1 exacerbates concanavalin A-induced hepatic injury in mice[J]. J Mol Med (Berl), 2010, 88(12):1289-1298.

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Hesperidin Inhibits High Mobility Group Protein B1 Releasing and Attenuates Acetaminophen-induced Hepatitis in Mice

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