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BMC Complementary Medicine and Therapies

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Open Access 01-12-2021 | Research article

Curcumin protects radiation-induced liver damage in rats through the NF-κB signaling pathway

Authors: Wei Li, Liangjun Jiang, Xianzhou Lu, Xianrong Liu, Mingjiong Ling

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

Abstract

Background

Curcumin has been demonstrated to exert anti-oxidant, anti-fibrotic, anti-inflammatory, and anti-cancer activities. This study was conducted to observe the effect and inner mechanism of curcumin in rats with radiation-induced liver damage (RILD).

Methods

Thirty SD rats were classified into Control, Radiation group and Curcumin (Cur) + Radiation group (n = 10 in each group). The changes in body weight of the rats were observed on the 3rd, 7th and 14th days after the treatment with curcumin. On the 14th day post treatment, the heart blood of the rats was drawn for measurement of liver function indices including total protein (TP), alanine aminotransfetase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) as well as aspartate aminotransfetase (AST). Subsequently, the rats were euthanized and liver tissues were taken to observe liver morphological changes using hematoxylin-eosin (HE), and to analyze apoptosis condition using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assays. Meanwhile, the oxidative stress level in liver tissue homogenate was determined by biochemical analysis. The expression of nuclear factor kappa B (NF-κB) pathway-associated and apoptosis-associated proteins was detected using Western blot analysis, and the expression levels of inflammatory factors were measured by Enzyme-linked immunosorbent assay (ELISA).

Results

The reduced body weight was observed in rats of the Radiation group compared to the Control and Cur + Radiation groups on day 14. In the Radiation group, hepatic cell edema and inflammatory cell infiltration could be visible under the light microscope, and the hepatocytes presented with vacuolar degeneration. In the Cur + Radiation group, the hepatocytes swelled under the microscope, but the pathological changes were alleviated in comparison with the Radiation group. RILD rats with curcumin treatment presented with decreased ALT, AST, ALP, LDH, and maleicdialdehyde (MDA) levels, and elevated TP, superoxide dismutase (SOD), caspase activated DNase (CAD) and glutathione (GSH) levels. Apoptosis and inflammation in rats with RILD were up-regulated, and the NF-κB pathway was activated, but they were reversed after continuously intragastric administration of curcumin for 14 days.

Conclusion

Our study highlights that curcumin treatment reduces the liver damage caused by radiation through the inhibition of the NF-κB pathway.

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Sossey-Alaoui K, Pluskota E, Szpak D, Schiemann WP, Plow EF. The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b. Sci Rep. 2018;8(1):7360.PubMedPubMedCentralCrossRef

Nakajima T, Ninomiya Y, Nenoi M: Radiation-Induced Reactions in The Liver - Modulation of Radiation Effects by Lifestyle-Related Factors. Int J Mol Sci. 2018;19(12):3855.

Cheng W, Xiao L, Ainiwaer A, Wang Y, Wu G, Mao R, Yang Y, Bao Y. Molecular responses of radiation-induced liver damage in rats. Mol Med Rep. 2015;11(4):2592–600.PubMedCrossRef

Han NK, Jung MG, Jeong YJ, Son Y, Han SC, Park S, Lim YB, Lee YJ, Kim SH, Park SC et al: Plasma Fibrinogen-Like 1 as a Potential Biomarker for Radiation-Induced Liver Injury. Cells. 2019;8(9):1042.

Patyar RR, Patyar S. Role of drugs in the prevention and amelioration of radiation induced toxic effects. Eur J Pharmacol. 2018;819:207–16.PubMedCrossRef

Panahi Y, Rahimnia AR, Sharafi M, Alishiri G, Saburi A, Sahebkar A. Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial. Phytother Res. 2014;28:1625–31.PubMedCrossRef

Afrin R, Arumugam S, Rahman A, Wahed MI, Karuppagounder V, Harima M, Suzuki H, Miyashita S, Suzuki K, Yoneyama H, et al. Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-kappaB translocation. Int Immunopharmacol. 2017;44:174–82.PubMedCrossRef

Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-Tortosa M. Curcumin and health. Molecules. 2016;21(3):264.PubMedPubMedCentralCrossRef

Kunnumakkara AB, Bordoloi D, Padmavathi G, Monisha J, Roy NK, Prasad S, Aggarwal BB. Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. Br J Pharmacol. 2017;174(11):1325–48.PubMedCrossRef

10.

Granados-Castro LF, Rodríguez-Rangel DS, Fernández-Rojas B, León-Contreras JC, Hernández-Pando R, Medina-Campos ON, Eugenio-Pérez D, Pinzón E, Pedraza-Chaverri J. Curcumin prevents paracetamol-induced liver mitochondrial alterations. J Pharm Pharmacol. 2016;68(2):245–56.PubMedCrossRef

11.

Gu Q, Guan H, Shi Q, Zhang Y, Yang H. Curcumin attenuated acute Propionibacterium acnes-induced liver injury through inhibition of HMGB1 expression in mice. Int Immunopharmacol. 2015;24(2):159–65.PubMedCrossRef

12.

Bruck R, Ashkenazi M, Weiss S, Goldiner I, Shapiro H, Aeed H, et al. Prevention of liver cirrhosis in rats by curcumin. Liver Int. 2007;27:373–83.PubMedCrossRef

13.

Park EJ, Jeon CH, Ko G, Kim J, Sohn DH. Protective effect of curcumin in rat liver injury induced by carbon tetrachloride. J Pharm Pharmacol. 2000;52(4):437–40.PubMedCrossRef

14.

Cai Y, Lu D, Zou Y, Zhou C, Liu H, Tu C, Li F, Liu L, Zhang S. Curcumin protects against intestinal origin Endotoxemia in rat liver cirrhosis by targeting PCSK9. J Food Sci. 2017;82(3):772–80.PubMedCrossRef

15.

Uzunhisarcikli M, Aslanturk A. Hepatoprotective effects of curcumin and taurine against bisphenol A-induced liver injury in rats. Environ Sci Pollut Res Int. 2019;26(36):37242–53.PubMedCrossRef

16.

Xie YL, Chu JG, Jian XM, Dong JZ, Wang LP, Li GX, Yang NB. Curcumin attenuates lipopolysaccharide/d-galactosamine-induced acute liver injury by activating Nrf2 nuclear translocation and inhibiting NF-kB activation. Biomed Pharmacother. 2017;91:70–7.PubMedCrossRef

17.

Ding GR, Honda N, Nakahara T, Tian F, Yoshida M, Hirose H, Miyakoshi J. Radiosensitization by inhibition of IkappaB-alpha phosphorylation in human glioma cells. Radiat Res. 2003;160(2):232–7.PubMedCrossRef

18.

Rivera-Espinoza Y, Muriel P. Pharmacological actions of curcumin in liver diseases or damage. Liver Int. 2009;29:1457–66.PubMedCrossRef

19.

Nabavi SF, Daglia M, Moghaddam AH, Habtemariam S, Nabavi SM. Curcumin and liver disease: from chemistry to medicine. Compr Rev Food Sci Food Saf. 2014;13:62–77.CrossRefPubMed

20.

Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Thomas P, Dannenberg AJ. Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-kappa B-dependent genes. Am J Physiol Gastrointest Liver Physiol. 2003;284(2):G321–7.PubMedCrossRef

21.

Verma V. Relationship and interactions of curcumin with radiation therapy. World J Clin Oncol. 2016;7(3):275–83.PubMedPubMedCentralCrossRef

22.

Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG, Group NCRRGW. Animal research: reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol. 2010;160(7):1577–9.PubMedPubMedCentralCrossRef

23.

McGrath JC, Drummond GB, McLachlan EM, Kilkenny C, Wainwright CL. Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br J Pharmacol. 2010;160(7):1573–6.PubMedPubMedCentralCrossRef

24.

Ding XQ, Gu TT, Wang W, Song L, Chen TY, Xue QC, Zhou F, Li JM, Kong LD. Curcumin protects against fructose-induced podocyte insulin signaling impairment through upregulation of miR-206. Mol Nutr Food Res. 2015;59(12):2355–70.PubMedCrossRef

25.

Ding XQ, Wu WY, Jiao RQ, Gu TT, Xu Q, Pan Y, Kong LD. Curcumin and allopurinol ameliorate fructose-induced hepatic inflammation in rats via miR-200a-mediated TXNIP/NLRP3 inflammasome inhibition. Pharmacol Res. 2018;137:64–75.PubMedCrossRef

26.

Pan CC, Kavanagh BD, Dawson LA, Li XA, Das SK, Miften M, Ten Haken RK. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S94–100.PubMedPubMedCentralCrossRef

27.

Peixoto A, Pereira P, Bessa de Melo R, Macedo G. radiation-induced liver disease secondary to adjuvant therapy for extra-hepatic cholangiocarcinoma. Dig Liver Dis. 2017;49(2):227.PubMedCrossRef

28.

Doi H, Shiomi H, Masai N, Tatsumi D, Igura T, Imai Y, Oh RJ. Threshold doses and prediction of visually apparent liver dysfunction after stereotactic body radiation therapy in cirrhotic and normal livers using magnetic resonance imaging. J Radiat Res. 2016;57(3):294–300.PubMedPubMedCentralCrossRef

29.

Sanuki N, Takeda A, Oku Y, Eriguchi T, Nishimura S, Aoki Y, Kunieda E. Influence of liver toxicities on prognosis after stereotactic body radiation therapy for hepatocellular carcinoma. Hepatol Res. 2015;45(5):540–7.PubMedCrossRef

30.

Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. Adv Exp Med Biol. 2007;595:1–75.PubMedCrossRef

31.

Ghorbani Z, Hekmatdoost A, Mirmiran P. Anti-hyperglycemic and insulin sensitizer effects of turmeric and its principle constituent curcumin. Int J Endocrinol Metab. 2014;12(4):e18081.PubMedPubMedCentralCrossRef

32.

Somparn P, Phisalaphong C, Nakornchai S, Unchern S, Morales NP. Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. Biol Pharm Bull. 2007;30(1):74–8.PubMedCrossRef

33.

Tawfik SS, Abouelella AM, Shahein YE. Curcumin protection activities against γ-rays-induced molecular and biochemical lesions. BMC Res Notes. 2013;6:375.PubMedPubMedCentralCrossRef

34.

Wang ME, Chen YC, Chen IS, Hsieh SC, Chen SS, Chiu CH. Curcumin protects against thioacetamide-induced hepatic fibrosis by attenuating the inflammatory response and inducing apoptosis of damaged hepatocytes. J Nutr Biochem. 2012;23(10):1352–66.PubMedCrossRef

35.

Fuchs-Tarlovsky V. Role of antioxidants in cancer therapy. Nutrition. 2013;29(1):15–21.PubMedCrossRef

36.

Shirazi A, Mihandoost E, Ghobadi G, Mohseni M, Ghazi-Khansari M. Evaluation of radio-protective effect of melatonin on whole body irradiation induced liver tissue damage. Cell J. 2013;14(4):292–7.PubMedPubMedCentral

37.

Farzaei MH, Zobeiri M, Parvizi F, El-Senduny FF, Marmouzi I, Coy-Barrera E, Naseri R, Nabavi SM, Rahimi R, Abdollahi M. Curcumin in liver diseases: a systematic review of the cellular mechanisms of oxidative stress and clinical perspective. Nutrients. 2018;10(7):855.PubMedCentralCrossRef

38.

Jagetia GC. Radioprotection and radiosensitization by curcumin. Adv Exp Med Biol. 2007;595:301–20.PubMedCrossRef

39.

Gisone P, Dubner D, Del Pérez RM, Michelin S, Puntarulo S. The role of nitric oxide in the radiation-induced effects in the developing brain. In Vivo. 2004;18(3):281–92.PubMed

40.

Srinivasan M, Sudheer AR, Rajasekaran KN, Menon VP. Effect of curcumin analog on gamma-radiation-induced cellular changes in primary culture of isolated rat hepatocytes in vitro. Chem Biol Interact. 2008;176(1):1–8.PubMedCrossRef

41.

Srinivasan M, Sudheer AR, Pillai KR, Kumar PR, Sudhakaran PR, Menon VP. Modulatory effects of curcumin on gamma-radiation-induced cellular damage in primary culture of isolated rat hepatocytes. Environ Toxicol Pharmacol. 2007;24(2):98–105.PubMedCrossRef

42.

Allison DJ, Ditor DS. Immune dysfunction and chronic inflammation following spinal cord injury. Spinal Cord. 2014;53:14–8.PubMedCrossRef

43.

He Y, Yue Y, Zheng X, Zhang K, Chen S, Du Z. Curcumin, inflammation, and chronic diseases: how are they linked? Molecules. 2015;20(5):9183–213.PubMedPubMedCentralCrossRef

44.

Sikora E, Scapagnini G, Barbagallo M. Curcumin, inflammation, ageing and age-related diseases. Immun Ageing. 2010;7:1–4.PubMedPubMedCentralCrossRef

45.

Saadati S, Sadeghi A, Mansour A, Yari Z, Poustchi H, Hedayati M, Hatami B, Hekmatdoost A. Curcumin and inflammation in non-alcoholic fatty liver disease: a randomized, placebo controlled clinical trial. BMC Gastroenterol. 2019;19(1):133.PubMedPubMedCentralCrossRef

46.

Wang Q, Ye C, Sun S, Li R, Shi X, Wang S, Zeng X, Kuang N, Liu Y, Shi Q, et al. Curcumin attenuates collagen-induced rat arthritis via anti-inflammatory and apoptotic effects. Int Immunopharmacol. 2019;72:292–300.PubMedCrossRef

47.

Liczbinski P, Michalowicz J, Bukowska B. Molecular mechanism of curcumin action in signaling pathways: review of the latest research. Phytother Res. 2020;34(8):1992–2005.PubMedCrossRef

48.

Liu Y, Zhang W, Cheng Y, Miao C, Gong J, Wang M. Activation of PPARgamma by Curcumin protects mice from ischemia/reperfusion injury induced by orthotopic liver transplantation via modulating polarization of Kupffer cells. Int Immunopharmacol. 2018;62:270–6.PubMedCrossRef

49.

Marquardt JU, Gomez-Quiroz L, Arreguin Camacho LO, Pinna F, Lee YH, Kitade M, et al. Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer. J Hepatol. 2015;63(3):661–9.PubMedPubMedCentralCrossRef

50.

Hesari A, Ghasemi F, Salarinia R, Biglari H, Tabar Molla Hassan A, Abdoli V, Mirzaei H. Effects of curcumin on NF-κB, AP-1, and Wnt/β-catenin signaling pathway in hepatitis B virus infection. J Cell Biochem. 2018;119(10):7898–904.PubMedCrossRef

51.

Rafiee P, Binion DG, Wellner M, Behmaram B, Floer M, Mitton E, Nie L, Zhang Z, Otterson MF. Modulatory effect of curcumin on survival of irradiated human intestinal microvascular endothelial cells: role of Akt/mTOR and NF-{kappa}B. Am J Physiol Gastrointest Liver Physiol. 2010;298(6):G865–77.PubMedPubMedCentralCrossRef

52.

He J, Niu Y, Wang F, Wang C, Cui T, Bai K, Zhang J, Zhong X, Zhang L, Wang T. Dietary curcumin supplementation attenuates inflammation, hepatic injury and oxidative damage in a rat model of intra-uterine growth retardation. Br J Nutr. 2018;120(5):537–48.PubMedCrossRef

53.

Aggarwal S, Ichikawa H, Takada Y, Sandur SK, Shishodia S, Aggarwal BB. Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IkappaBalpha kinase and Akt activation. Mol Pharmacol. 2006;69(1):195–206.PubMedCrossRef

54.

Cao L, Ding W, Du J, Jia R, Liu Y, Zhao C, Shen Y, Yin G. Effects of curcumin on antioxidative activities and cytokine production in Jian carp (Cyprinus carpio var. Jian) with CCl4-induced liver damage. Fish Shellfish Immunol. 2015;43(1):150–7.PubMedCrossRef

Title: Curcumin protects radiation-induced liver damage in rats through the NF-κB signaling pathway
Authors: Wei Li
Liangjun Jiang
Xianzhou Lu
Xianrong Liu
Mingjiong Ling
Publication date: 01-12-2021
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-020-03182-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Curcumin protects radiation-induced liver damage in rats through the NF-κB signaling pathway

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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