Curcumin Alleviates Potassium Bromate-Induced Hepatic Damage by Repressing CRP Induction through TNF-α and IL-1β and by Suppressing Oxidative Stress
This study evaluated the prospective molecular and biochemical mechanisms behind the hepatoprotective effects of curcumin in Wistar rats exposed to KBrO3. Techniques for assessment of hepatic oxidative injury and histological biomarkers were used. The concentrations of proteins connected with inflammation (e.g. tumor necrosis factor-alpha (TNF-α), interleukins 1β (IL-1β) and C-reactive protein (CRP)) were estimated by enzyme-linked immunosorbent assay (ELISA) techniques. Results showed that, curcumin administered orally at a dose of 20 mg/kg for 28 days significantly suppressed the activities of serum transaminases and alkaline induced by KBrO3 administration (20 mg/kg, twice weekly) and protected the integrity of the liver tissue. Also, curcumin at the tested dose abridged the KBrO3-induced increase in hepatic malondialdehyde (MDA) levels and reversed KBrO3 mediated reduction in activities of hepatic antioxidant molecules including reduced glutathione (GSH), total thiol (TSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD). In addition, curcumin significantly assuaged inflammatory response in KBrO3-lesioned liver as revealed by the decrease in inflammatory biomarkers. This study suggests that curcumin exhibits a protective effect via induction of hepatic detoxification proteins and inhibition of inflammatory proteins in addition to its antioxidative ability in KBrO3- induced hepatic injury in rats.
Ahmad MK, Khan AA, Ali SN, Mahmood R (2015). Chemoprotective effect of taurine on potassium bromate-induced DNA damage, DNA-protein cross-linking and oxidative stress in rat intestine. PloS One 10(3):e0119137.
Akinyemi AJ, Onyebueke N, Faboya OA, Onikanni SA, Fadaka A, Olayide I (2017). Curcumin inhibits adenosine deaminase and arginase activities in cadmium-induced renal toxicity in rat kidney. Journal of Food and Drug Analysis 25(2):438-446.
Ammon HP, Wahl MA (1991). Pharmacology of Curcuma longa. Planta Medica 57(1):1-7.
Araujo CAC, Leon LL (2001). Biological activities of Curcuma longa L. Memorias do Instituto Oswaldo Cruz 96(5):723-728.
Ayala A, Muñoz MF, Argüelles S (2014). Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity 2014:1-31.
Balkwill F, Mantovani A (2001). Inflammation and cancer: back to Virchow? Lancet 357:539-45.
Bayomy NA, Soliman GM, Abdelaziz EZ (2016). Effect of potassium bromate on the liver of adult male albino rat and a possible protective role of vitamin C: histological, immunohistochemical, and biochemical study. The Anatomical Record 299(9):1256-1269.
Cai Y, Lu D, Zou Y, Zhou C, Liu H, Tu C, ... Zhang S (2017). Curcumin protects against intestinal origin endotoxemia in rat liver cirrhosis by targeting PCSK9. Journal of Food Science 82(3):772-780.
Castell JV, Gomez-Lechon MJ, David M, Fabra R, Trullenque R, Heinrich PC (1990). Acute-phase response of human hepatocytes; regulation of acute-phase protein synthesis by interleukin-6. Hepatology 12:1179-1186.
Chipman J, Davies J, Parsons J, Nair G, O’Neill J, Fawell J (1998). DNA oxidation by potassium bromate; a direct mechanism or linked to lipid peroxidation? Toxicology 126:93-102.
Clevers H (2004). At the crossroads of inflammation and cancer. Cell 118:671-674.
Crumley ABC, McMillan DC, McKernan M, Going JJ, Shearer CJ, Stuart RC (2006). An elevated C-reactive protein concentration, prior to surgery, predicts poor cancer-specific survival in patients undergoing resection for gastrooesophageal cancer. British Journal of Cancer 94:1568-71
De Mello J, Struthers L, Turner R, Cooper EH, Giles GR (1983). Multivariate analyses as aids to diagnosis and assessment of prognosis in gastrointestinal cancer. British Journal of Cancer 48:341-348.
DeAngelo AB, George MH, Kilburn SR, Moore TM, Wolf DC (1998). Carcinogenicity of potassium bromate administered in the drinking water to male B6C3F1 mice and F344/N rats. Toxicologic Pathology 26(5):587-594.
DeCicco LA, Rikans LE, Tutor CG, Hornbrook KR (1998). Serum and liver concentrations of tumor necrosis factor α and interleukin-1β following administration of carbon tetrachloride to male rats. Toxicology Letters 98(1-2):115-121.
Elmansi AM, El-Karef AA, El-Shishtawy MM, Eissa LA (2017). Hepatoprotective effect of curcumin on hepatocellular carcinoma through autophagic and apoptic pathways. Annals of Hepatology 16(4):607-618.
Englehardt A (1970). Measurement of alkaline phosphatase. Aerztl Labor 16(42):1.
Falconer JS, Fearson KC, Ross JA, Elton R, Wigmore SJ, Garden OJ, Carter DC (1995). Acute-phase protein response and survival duration of patients with pancreatic cancer. Cancer 75:2077-82.
Farombi EO, Shrotriya S, Surh YJ (2009). Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-κB and AP-1. Life Sciences 84(5-6):149-155.
Fürst R, Zündorf I (2014). Plant-derived anti-inflammatory compounds: hopes and disappointments regarding the translation of preclinical knowledge into clinical progress. Mediators of Inflammation 2014(1):146832.
Gockel I, Dirksen K, Messow CM, Junginger T (2006). Significance of preoperative C-reactive protein as a parameter of the perioperative course and long-term prognosis in squamous cell carcinoma and adenocarcinoma of the oesophagus. World Journal of Gastroenterology 12:3746-50.
Gornall AG, Bardawill CJ, David MM (1949). Determination of serum proteins by means of the biuret reaction. Journal of Biological Chemistry 177(2):751-766.
Grant GH (1987). Amino acids and protein; fundamentals of clinical chemistry. In: Tietz NW (Ed). WB Saunders Company Philadelphia USA pp 328-329.
Griffiths K, Aggarwal B, Singh R, Buttar H, Wilson D, De Meester F (2016). Food antioxidants and their anti-inflammatory properties: a potential role in cardiovascular diseases and cancer prevention. Diseases 4(3):28.
Jollow DJ, Mitchell JR, Zampaglione NA, Gillette JR (1974). Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11(3):151-169.
Kennon S, Price CP, Mills PG, Ranjadayalan K, Cooper J, Clarke H, Timmis AD (2001). The effect of aspirin on C-reactive protein as a marker of risk in unstable angina. Journal of the American College of Cardiology 37:1266-1270.
Khan RA, Khan MR, Sahreen S (2012). Protective effects of rutin against potassium bromate induced nephrotoxicity in rats. BMC complementary and alternative Medicine 12(1):204.
Kyung EJ, Kim HB, Hwang, ES, Lee S, Choi BK, Kim JW, ... Woo EJ (2018). Evaluation of hepatoprotective effect of curcumin on liver cirrhosis using a combination of biochemical analysis and magnetic resonance-based electrical conductivity imaging. Mediators of Inflammation 5491797.
Lee JC, Kundu JK, Hwang DM, Na HK, Surh YJ (2007). Humulone inhibits phorbol ester-induced COX-2 expression in mouse skin by blocking activation of NF-κB and AP-1: IκB kinase and c-Jun-N-terminal kinase as respective potential upstream targets. Carcinogenesis 28(7):1491-1498.
Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, Feng Y (2015). The role of oxidative stress and antioxidants in liver diseases. International Journal of Molecular Sciences 16(11):26087-26124.
Maheshwari RK, Singh AK, Gaddipati J, Srimal RC (2006). Multiple biological activities of curcumin: A short review. Life Sciences 78(18):2081-2087.
Manubolu M, Goodla L, Ravilla S, Thanasekaran J, Dutta P, Malmlöf K, Obulum VR (2014). Protective effect of Actiniopteris radiata (Sw.) Link. against CCl4 induced oxidative stress in albino rats. Journal of Ethnopharmacology 153(3):744-752.
Misra HP, Fridovich I (1972). The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. Journal of Biological Chemistry 247(10):3170-3175.
Mohajeri M, Rezaee M, Sahebkar A (2017). Cadmium‐induced toxicity is rescued by curcumin: a review. Biofactors 43(5):645-661.
Murata M, Bansho Y, Inoue S, Ito K, Ohnishi S, Midorikawa K, Kawanashi S (2001). Requirement of glutathione and cysteine in guanine-specific oxidation of DNA by carcinogenic potassium bromated. Chemical Research in Toxicology 14:678-685.
Nakae D, Kobayashi Y, Akai H, Andoh N, Satoh H, Ohashi K, … Konishi Y (1997). Involvement of 8-hydroxyguanine formation in the initiation of rat liver carcinogenesis by low dose levels of N-nitrosodiethylamine. Cancer Research 57:1281-1287.
NCI D (1996). Clinical development plan: curcumin. Journal of Cellular Biochemistry Supplement 26:72-85.
Nissen SE, Tuzcu EM, Schoenhagen P, Crowe T, Sasiela WJ, Tsai J, … Ganz P (2005). Reversal of atherosclerosis with aggressive lipid lowering (REVERSAL) investigators. statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. New England Journal of Medicine 352:29-38.
Obaidi, I, Higgins M, Bahar B, Davis JL, McMorrow T (2018). Identification of the multifaceted chemopreventive activity of curcumin against the carcinogenic potential of the food additive, KBrO3. Current Pharmaceutical Design 24(5):595-614.
Ohkawa H, Ohishi N, Yagi K (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 95(2):351-358.
Otuechere CA, Abarikwu SO, Olateju VI, Animashaun AL, Kale OE (2014). Protective effect of curcumin against the liver toxicity caused by propanil in rats. International Scholarly Research Notices 2014:853697.
Paglia DE, Valentine WN (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. The Journal of Laboratory and Clinical Medicine 70(1):158-169.
Perwez Hussain S, Harris CC (2007). Inflammation and cancer: an ancient link with novel potentials. International Journal of Cancer 121(11):2373-2380.
Pradeep K, Mohan CV, Gobianand K, Karthikeyan S (2007). Effect of Cassia fistula Linn. leaf extract on diethylnitrosamine induced hepatic injury in rats. Chemico Biological Interaction 167:12-18.
Prasad K (2006). C-reactive protein (CRP)-lowering agents. Cardiovascular Drug Review 24:33-50.
Reitman S, Frankel S (1957). A colorimetric method for determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. American Journal of Clinical Pathology 28:56-62.
Sahreen S, Khan MR, Khan RA, Shah NA (2013). Effect of Carissa opaca leaves extract on lipid peroxidation, antioxidant activity and reproductive hormones in male rats. Lipids in Health and Disease 12(1):90.
Starek A, Beata S (2016). Toxicological properties of potassium bromate. Journal of Pharmaceutical Reports 1:1-9.
Surh YJ (2003). Cancer chemoprevention with dietary phytochemicals. Nature Reviews Cancer 3(10):768-780.
Surh YJ, Kundu JK, Na HK, Lee JS (2005). Redox-sensitive transcription factors as prime targets for chemoprevention with anti-inflammatory and antioxidative phytochemicals. Journal of Nutrition 135:2993S-3001S.
Tsuchiya T, Kijima A, Ishii Y, Takasu S, Yokoo Y, Nishikawa A, ... Umemura T (2018). Mechanisms of oxidative stress-induced in vivo mutagenicity by potassium bromate and nitrofurantoin. Journal of Toxicologic Ppathology 31(3):179-188.
Uchida T, Sakashita Y, Kitahata K, Yamashita Y, Tomida C, Kimori Y, … Higashitani A (2018). Reactive oxygen species upregulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells. American Journal of Physiology-Cell Physiology 314(6):C721-731.
Umemura T, Takagi A, Sai K, Hasegawa R, Kurokawa Y (1998). Oxidative DNA damage and cell proliferation in kidneys of male and female rats during 13-weeks exposure to potassium bromate (KBrO3). Archives of Toxicology 72:264-269.
Wang CS, Sun CF (2009). C-reactive protein and malignancy: clinico-pathological association and therapeutic implication. Chang Gung Medical Journal 32(5):471-482.
Wills PJ, Suresh V, Arun M, Asha VV (2006). Antiangiogenic effect of Lygodium flexuosum against N-nitrosodiethylamine-induced hepatotoxicity in rats. Chemico-Biological Interaction 164:25-38.
Zhang X, De Silva D, Sun B, Fisher J, Bull RJ, Cotruvo JA, Cummings BS (2010). Cellular and molecular mechanisms of bromate-induced cytotoxicity in human and rat kidney cells. Toxicology 269(1):13-23.
Zhou Z, Xu MJ, Gao B (2016). Hepatocytes: a key cell type for innate immunity. Cellular and Molecular Immunology 13(3):301-315.
Zimmerman MA, Selzman CH, Cothren C, Sorensen AC, Raeburn CD, Harken AH (2003). Diagnostic implications of C-reactive protein. Archives of Surgery 138:220-224.
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