Hormetic effects of curcumin on oxidative stress injury induced by trivalent arsenic in isolated rat hepatocytes

Document Type : Original Research Article

Authors

1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran

2 Traditional Medicine and Materia Medica Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Department of English Language, Faculty of Humanities, University of Zabol, Sistan and Balouchestan, Zabol, Iran

4 International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Central Tehran Branch, Islamic Azad University, Tehran, Iran

6 Clinical Research Development Unit, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective: Arsenic (As) poisoning is a worldwide public health problem. Arsenic can cause cancer, diabetes, hepatic problems, etc. Hence, we investigated possible hepatoprotective properties of curcumin against As3+-induced liver damages in freshly isolated rat hepatocytes.
Materials and Methods: Isolation of hepatocytes was done by the two-step liver perfusion method using collagenase. The EC50 concentration of As3+ was used in toxicity assessments and curcumin (2, 5, and 10 µM) was added 15 min before As3+ addition to isolated hepatocytes. Curcumin impact was assessed in terms of cytotoxicity, lipid peroxidation induction, reactive oxygen species (ROS) levels, and mitochondrial membrane potential.
Results: As3+ significantly increased cytotoxicity, malondialdehyde and ROS levels and induced mitochondrial membrane damage and hepatocyte membrane lysis after 3 hr incubation. Curcumin 2 µM significantly prevented lipid peroxidation induction, ROS formation, and mitochondrial membrane damage; while curcumin 5 µM had no apparent effect on these parameters, curcumin 10 µM potentiated them.
Conclusion: Curcumin only at low doses could ameliorate oxidative stress injury induced by As3+ in isolated rat hepatocytes.

Keywords

Main Subjects


Balarastaghi S, Rezaee R, Hayes AW,
Yarmohammadi F, Karimi G. 2022.
Mechanisms of arsenic exposure-induced
hypertension and atherosclerosis: An
updated overview. Biological Trace
Element Research, 201: 98-113.
Baum L, Cheung SK, Mok VC, Lam LC,
Leung VP, Hui E, Ng CC, Chow M, Ho
PC, Lam S. 2007. Curcumin effects on
blood lipid profile in a 6-month human
study. Pharmacol Res, 56: 509-514.
Bengmark S. 2006. Curcumin, an atoxic
antioxidant and natural NFκB,
cyclooxygenase-2, lipooxygenase, and
inducible nitric oxide synthase inhibitor: a
shield against acute and chronic diseases.
J Parenter Enteral Nutr, 30: 45-51.
Burgos‐Morón E, Calderón‐Montaño JM,
Salvador J, Robles A, López‐Lázaro M.
2010. The dark side of curcumin. Int J
Cancer, 126: 1771-1775.
Cao J, Jia L, Zhou H-M, Liu Y, Zhong L-F.
2006. Mitochondrial and nuclear DNA
damage induced by curcumin in human
hepatoma G2 cells. Toxicol Sci, 91: 476-
483.
Cilla A, Laparra JM, Alegria A, Barbera R,
Farre R. 2008. Antioxidant effect derived
from bioaccessible fractions of fruit
beverages against H 2 O 2-induced
oxidative stress in Caco-2 cells. Food
Chem, 106: 1180-1187.
De Vizcaya-Ruiz A, Barbier O, Ruiz-Ramos
R, Cebrian ME. 2009. Biomarkers of
oxidative stress and damage in human
populations exposed to arsenic. Mutat
Res, 674: 85-92.
Famurewa AC, Maduagwuna EK, Aloke C,
Azubuike-Osu SO, Narayanankutty A.
2022. Virgin coconut oil ameliorates
arsenic hepatorenal toxicity and NOmediated inflammation through
suppression of oxidative stress in rats.
TJPS, 46: 167-172.
Farzaei MH, Zobeiri M, Parvizi F, El-Senduny
FF, Marmouzi I, Coy-Barrera E, Naseri
R, Nabavi SM, Rahimi R, Abdollahi M.
2018. Curcumin in liver diseases: a
systematic review of the cellular
mechanisms of oxidative stress and
clinical perspective. Nutrients, 10: 855.
Flora SJ. 2011. Arsenic-induced oxidative
stress and its reversibility. Free Radic
Biol Med, 51: 257-281.
García-Niño WR, Pedraza-Chaverrí J. 2014.
Protective effect of curcumin against
heavy metals-induced liver damage. Food
Chem Toxicol, 69: 182-201.
Gülçin İ. 2012. Antioxidant activity of food
constituents: an overview. Arch Toxicol,
86: 345-391.
Hashemzaei M, Pourahmad J, Safaeinejad F,
Tabrizian K, Akbari F, Bagheri G,
Hosseini M-J, Shahraki J. 2015.
Antimony induces oxidative stress and
cell death in normal hepatocytes. Toxicol
Environ Chem, 97: 256-265.
Hashemzaei M, Tabrizian K, Alizadeh Z,
Pasandideh S, Rezaee R, Mamoulakis C,
Tsatsakis A, Skaperda Z, Kouretas D,
Shahraki J. 2020. Resveratrol, curcumin
and gallic acid attenuate glyoxal-induced
damage to rat renal cells. Toxicol Rep, 7:
1571-1577.
Hassani S, Sepand M, Jafari A, Jaafari J,
Rezaee R, Zeinali M, Tavakoli F, RazaviAzarkhiavi K. 2015. Protective effects of
curcumin and vitamin E against
chlorpyrifos-induced lung oxidative
damage. Hum Exp Toxicol, 34: 668-676.
Hatcher H, Planalp R, Cho J, Torti F, Torti S.
2008. Curcumin: from ancient medicine
to current clinical trials. Cell Mol Life
Sci, 65: 1631-1652.
Herbert KJ, Snow ET. 2012. Modulation of
arsenic-induced epidermal growth factor
receptor pathway signalling by
resveratrol. Chem Biol Interact, 198: 38-
48.
Hou Y, Wang Y, Wang H, Xu Y. 2014.
Induction of glutathione synthesis in
human hepatocytes by acute and chronic
arsenic exposure: Differential roles of
mitogen-activated protein kinases.
Toxicology, 325: 96-106.
Janasik B, Reszka E, Stanislawska M,
Jablonska E, Kuras R, Wieczorek E,
Malachowska B, Fendler W, Wasowicz
W. 2018. Effect of arsenic exposure on
NRF2-KEAP1 pathway and epigenetic
modification. Biol Trace Elem Res, 185:
11-19.
Järup L. 2003. Hazards of heavy metal
Curcumin exerts hormetic effects on arsenic toxicity
Epub ahead of print 9
contamination. Br Med Bull, 68: 167-182.
Job JT, Rajagopal R, Alfarhan A, Kim YO,
Kim H-J, Narayanankutty A. 2022a.
Protective effect of borassus flabellifer
haustorium extract against alkoxyl
radical-induced cytotoxicity by improving
glutathione metabolism by modulating
nrf2/haeme oxygenase-1 expression. J
Am Coll Nutr, 41: 587-593.
Job JT, Rajagopal R, Alfarhan A,
Narayanankutty A. 2022b. Borassus
flabellifer Linn haustorium methanol
extract mitigates fluoride-induced
apoptosis by enhancing Nrf2/Haeme
oxygenase 1–dependent glutathione
metabolism in intestinal epithelial cells.
Drug Chem Toxicol, 45: 2269-2275.
Jomova K, Jenisova Z, Feszterova M, Baros S,
Liska J, Hudecova D, Rhodes C, Valko
M. 2011. Arsenic: toxicity, oxidative
stress and human disease. J Appl Toxicol,
31: 95-107.
Kang J, Chen J, Shi Y, Jia J, Zhang Y. 2005.
Curcumin-induced histone
hypoacetylation: the role of reactive
oxygen species. Biochem Pharmacol, 69:
1205-1213.
Laparra JM, Vélez D, Barberá R, Granero L,
Polache A, Montoro R, Farré R. 2006.
Cytotoxic effect of As (III) in Caco-2
cells and evaluation of its human
intestinal permeability. Toxicol in Vitro,
20: 658-663.
Lee H-I, McGregor RA, Choi M-S, Seo K-I,
Jung UJ, Yeo J, Kim M-J, Lee M-K.
2013. Low doses of curcumin protect
alcohol-induced liver damage by
modulation of the alcohol metabolic
pathway, CYP2E1 and AMPK. Life Sci,
93: 693-699.
Liu J, Waalkes MP. 2008. Liver is a target of
arsenic carcinogenesis. Toxicol Sci, 105:
24-32.
Malayil D, House NC, Puthenparambil D, Job
JT, Narayanankutty A. 2022. Borassus
flabellifer haustorium extract prevents
pro-oxidant mediated cell death and LPSinduced inflammation. Drug Chem
Toxicol, 45: 1716-1722.
Mirzaei H, Naseri G, Rezaee R, Mohammadi
M, Banikazemi Z, Mirzaei HR, Salehi H,
Peyvandi M, Pawelek JM, Sahebkar A.
2016. Curcumin: A new candidate for
melanoma therapy? Int J Cancer, 139:
1683-1695.
Moghaddam NSA, Oskouie MN, Butler AE,
Petit PX, Barreto GE, Sahebkar A. 2019.
Hormetic effects of curcumin: What is the
evidence? J Cell Physiol, 234: 10060-
10071.
Moldeus P, Hogberg J, Orrenius S. 1978.
Isolation and use of liver cells. Methods
Enzymol, 52: 60-71.
Morisco F, Vitaglione P, Amoruso D, Russo
B, Fogliano V, Caporaso N. 2008. Foods
and liver health. Mol Asp Med, 29: 144-
150.
Najafi N, Rezaee R, Hayes AW, Karimi G.
2022. A review of mechanisms
underlying the protective effects of
natural compounds against arsenicinduced neurotoxicity. Biometals. [Online
ahead of print].
Narayanankutty A, Job JT, Narayanankutty V.
2019. Glutathione, an antioxidant
tripeptide: Dual roles in carcinogenesis
and chemoprevention. Curr Protein Pept
Sci, 20: 907-917.
Narayanankutty A, Nair A, Illam SP,
Upaganlawar A, Raghavamenon AC.
2021. Curcumin enriched VCO protects
against 7,12-Dimethyl Benz[a]
anthracene-induced skin papilloma in
mice. Nutr Cancer, 73: 809-816.
Rezaee R, Momtazi AA, Monemi A, Sahebkar
A. 2017. Curcumin: a potentially
powerful tool to reverse cisplatin-induced
toxicity. Pharmacol Res, 117: 218-227.
Shahraki J, Motallebi A, Aghvami M,
Pourahmad J. 2013a. Ichthyotoxic
cochlodinium polykrikoides induces
mitochondrial mediated oxidative stress
and apoptosis in rat liver hepatocytes. Iran
J Pharm Res, 12: 829-844.
Shahraki J, Motallebi A, Pourahmad J. 2013b.
Oxidative mechanisms of fish hepatocyte
toxicity by the harmful dinoflagellate
Cochlodinium polykrikoides. Mar
Environ Res, 87-88: 52-60.
Shahraki J, Zareh M, Kamalinejad M,
Pourahmad J. 2014. Cytoprotective
effects of hydrophilic and lipophilic
extracts of pistacia vera against oxidative
versus carbonyl stress in rat hepatocytes.
Iran J Pharm Res, 13: 1263-1277.
Sharma R, Gescher A, Steward W. 2005.
Curcumin: the story so far. Eur J Cancer,
41: 1955-1968.
Shi H, Shi X, Liu KJ. 2004. Oxidative
mechanism of arsenic toxicity and
Amirmostofian et al.
Epub ahead of print 10
carcinogenesis. Mol Cell Biochem, 255:
67-78.
Stamatelos SK, Androulakis IP, Kong A-NT,
Georgopoulos PG. 2013. A semimechanistic integrated toxicokinetic–
toxicodynamic (TK/TD) model for
arsenic (III) in hepatocytes. J Theor Biol,
317: 244-256.
Susan A, Rajendran K, Sathyasivam K,
Krishnan UM. 2019. An overview of
plant-based interventions to ameliorate
arsenic toxicity. Biomed Pharmacother,
109: 838-852.
Tabrizian K, Musavi S, Rigi M, Hosseindadi
F, Kordi S, Shamshirgaran F, Bazi A,
Shahraki J, Rezaee R, Hashemzaei M.
2019. Behavioral and molecular effects of
intrahippocampal infusion of auraptene,
resveratrol, and curcumin on H-89-
induced deficits on spatial memory
acquisition and retention in Morris water
maze. Hum Exp Toxicol, 38: 775-784.
Wilken R, Veena MS, Wang MB, Srivatsan
ES. 2011. Curcumin: A review of anticancer properties and therapeutic activity
in head and neck squamous cell
carcinoma. Mol Cancer, 10: 12.
Xu Y, Wang Y, Zheng Q, Li X, Li B, Jin Y,
Sun X, Sun G. 2008. Association of
oxidative stress with arsenic methylation
in chronic arsenic-exposed children and
adults. Toxicol Appl Pharmacol, 232:
142-149.
Yeang HXA, Hamdam JM, Al-Huseini LM,
Sethu S, Djouhri L, Walsh J,
Kitteringham N, Park BK, Goldring CE,
Sathish JG. 2012. Loss of transcription
factor nuclear factor-erythroid 2 (NF-E2)
p45-related factor-2 (Nrf2) leads to
dysregulation of immune functions, redox
homeostasis, and intracellular signaling in
dendritic cells. J Biol Chem, 287: 10556-
10564.