Quercetin Protected from Aluminum Phosphide-induced Acute and Subacute Cardio- and Hepatotoxicity in Rats

Page: [3513 - 3524] Pages: 12

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Abstract

Background: Aluminum phosphide (ALP) intoxication either accidentally or intentionally, is one of the major health concerns in developing countries. Its poisoning causes severe damage to organs including the heart and liver.

Objectives: This study aimed to investigate the hepato- and cardioprotective effects of quercetin (QCN) on the acute/subacute toxicity of ALP in rodent models.

Methods: Acute (single dose, 12.5 mg/kg, orally) and subacute (2 mg/kg, orally and 7 days) intoxication of ALP were induced in rats and the protective effects of QCN on altered hepatic/cardiac functional enzyme concentrations, myeloperoxidase activity, oxidative stress biomarkers, and histopathological changes were studied at three doses of 10, 50 and 100 mg/kg BW. To record any heart abnormality, an electrocardiogram (ECG) was recorded 3 h after the last treatment.

Results: Quercetin reduced the ALP-increased hepatic and cardiac functional enzyme concentrations and myeloperoxidase activity. Moreover, QCN improved remarkably the ALP-induced ECG abnormalities (T inversion, bigeminy in R waves) and arrhythmias. QCN attenuated significantly (p < 0.05) the ALP-induced oxidative/ nitrosative stress and histopathological injuries in the liver and heart.

Conclusion: Our results suggest that QCN is able to protect the ALP-induced cardiac and hepatic injuries in both acute and subacute models and its effects attribute to its antioxidant and anti-inflammatory properties.

[1]
Mehrpour O, Singh S. Rice tablet poisoning: A major concern in Iranian population. Hum Exp Toxicol 2010; 29(8): 701-2.
[http://dx.doi.org/10.1177/0960327109359643] [PMID: 20097728]
[2]
Soltaninejad K, Faryadi M, Sardari F. Acute pesticide poisoning related deaths in Tehran during the period 2003–2004. J Forensic Leg Med 2007; 14(6): 352-4.
[http://dx.doi.org/10.1016/j.jflm.2006.12.011] [PMID: 17631456]
[3]
Hosseinian A, Pakravan N, Rafiei A, Feyzbakhsh SM. Aluminum phosphide poisoning known as rice tablet: A common toxicity in North Iran. Indian J Med Sci 2011; 65(4): 143-50.
[http://dx.doi.org/10.4103/0019-5359.104777] [PMID: 23250344]
[4]
Singh S, Bhalla A, Verma SK, Kaur A, Gill K. Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol 2006; 44(2): 155-8.
[http://dx.doi.org/10.1080/15563650500514467] [PMID: 16615671]
[5]
Hosseini SF, Forouzesh M, Maleknia M, Valiyari S, Maniati M, Samimi A. The molecular mechanism of aluminum phosphide poisoning in cardiovascular disease: Pathophysiology and diagnostic approach. Cardiovasc Toxicol 2020; 20(5): 454-61.
[http://dx.doi.org/10.1007/s12012-020-09592-4] [PMID: 32712815]
[6]
Eric EU, Boloya VE, Osuamkpe AE. Aggravation of aluminum phosphide induced liver damage and hematotoxicity in adult wistar rat: The role of Allium Sativum. Euro J Biol Biotechnol 2021; 2(2): 51-9.
[http://dx.doi.org/10.24018/ejbio.2021.2.2.176]
[7]
Song X, Wang Y, Gao L. Mechanism of antioxidant properties of quercetin and quercetin-DNA complex. J Mol Model 2020; 26(6): 133.
[http://dx.doi.org/10.1007/s00894-020-04356-x] [PMID: 32399900]
[8]
Liao YR, Lin JY. Quercetin exerts anti-inflammatory effects via meanwhile suppressing TLR2 gene expression and STAT3 protein phosphorylation in activated inflammatory macrophages. J Explor Res Pharmacol 2020; 5(3): 31-41.
[http://dx.doi.org/10.14218/JERP.2020.00006]
[9]
Li Y, Yao J, Han C, et al. Quercetin, inflammation and immunity. Nutrients 2016; 8(3): 167.
[http://dx.doi.org/10.3390/nu8030167] [PMID: 26999194]
[10]
Asghari MH, Moloudizargari M, Baeeri M, et al. On the mechanisms of melatonin in protection of aluminum phosphide cardiotoxicity. Arch Toxicol 2017; 91(9): 3109-20.
[http://dx.doi.org/10.1007/s00204-017-1998-6] [PMID: 28551710]
[11]
Rahimi N, Abdolghaffari AH, Partoazar A, et al. Fresh red blood cells transfusion protects against aluminum phosphide-induced metabolic acidosis and mortality in rats. PLoS One 2018; 13(3): e0193991.
[http://dx.doi.org/10.1371/journal.pone.0193991] [PMID: 29590163]
[12]
Ranjbar A, Gholami L, Ghasemi H, Kheiripour N. Effects of nano-curcumin and curcumin on the oxidant and antioxidant system of the liver mitochondria in aluminum phosphide-induced experimental toxicity. Nanomed J 2020; 7: 58-64.
[13]
Torabi M, Karami-Mohajeri S, Mirzali R, Nematipour F, Ahmadi J, Ahamadi M. A promising method for the treatment of aluminum phosphide poisoning: An experimental study in rats. Iran J Pharmacol Ther 2017; 15: 1-6.
[14]
Xu Y, Han J, Dong J, et al. Metabolomics characterizes the effects and mechanisms of quercetin in nonalcoholic fatty liver disease development. Int J Mol Sci 2019; 20(5): 1220.
[http://dx.doi.org/10.3390/ijms20051220] [PMID: 30862046]
[15]
Cuzzocrea S, Ianaro A, Wayman NS, et al. The cyclopentenone prostaglandin 15-deoxy-Δ 12,14 - PGJ 2 attenuates the development of colon injury caused by dinitrobenzene sulphonic acid in the rat. Br J Pharmacol 2003; 138(4): 678-88.
[http://dx.doi.org/10.1038/sj.bjp.0705077] [PMID: 12598422]
[16]
Benzie IFF, Strain JJ. Ferric reducing/antioxidant power assay: Direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods Enzymol 1999; 299: 15-27.
[http://dx.doi.org/10.1016/S0076-6879(99)99005-5] [PMID: 9916193]
[17]
Niehaus WG Jr, Samuelsson B. Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 1968; 6(1): 126-30.
[http://dx.doi.org/10.1111/j.1432-1033.1968.tb00428.x] [PMID: 4387188]
[18]
Lowry O, Rosebrough N, Farr AL, Randall R. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-75.
[http://dx.doi.org/10.1016/S0021-9258(19)52451-6] [PMID: 14907713]
[19]
Hu ML. Measurement of protein thiol groups and glutathione in plasma. Methods Enzymol 1994; 233: 380-5.
[http://dx.doi.org/10.1016/S0076-6879(94)33044-1] [PMID: 8015473]
[20]
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 1982; 126(1): 131-8.
[http://dx.doi.org/10.1016/0003-2697(82)90118-X] [PMID: 7181105]
[21]
Omae K, Ishizuka C, Nakashima H, et al. Acute and subacute inhalation toxicity of highly purified phosphine (PH3) in male ICR mice. J Occup Health 1996; 38(1): 36-42.
[http://dx.doi.org/10.1539/joh.38.36]
[22]
Anand R, Sharma DR, Verma D, Bhalla A, Gill KD, Singh S. Mitochondrial electron transport chain complexes, catalase and markers of oxidative stress in platelets of patients with severe aluminum phosphide poisoning. Hum Exp Toxicol 2013; 32(8): 807-16.
[http://dx.doi.org/10.1177/0960327112468909] [PMID: 23821638]
[23]
Salimi A, Jamali Z, Shabani M. Antioxidant potential and inhibition of mitochondrial permeability transition pore by myricetin reduces aluminium phosphide-induced cytotoxicity and mitochondrial impairments. Front Pharmacol 2021; 12: 719081.
[http://dx.doi.org/10.3389/fphar.2021.719081] [PMID: 34858168]
[24]
Bogle RG, Theron P, Brooks P, Dargan PI, Redhead J. Aluminium phosphide poisoning. Emerg Med J 2006; 23(1): e03.
[http://dx.doi.org/10.1136/emj.2004.015941] [PMID: 16373788]
[25]
Salimi A, Kheiripour N, Fathi Jouzdani A, et al. Nanocurcumin improves lipid status, oxidative stress, and function of the liver in aluminium phosphide-induced toxicity: Cellular and molecular mechanisms. BioMed Res Int 2022; 2022: 1-13.
[http://dx.doi.org/10.1155/2022/7659765] [PMID: 36132078]
[26]
Suthar P, Shinde V, Ambad R, Kane SK, Ramdas PB. Study of cardiac markers in myocardial infraction parameters before and after treatment. ECS Trans 2022; 107(1): 15221-7.
[http://dx.doi.org/10.1149/10701.15221ecst]
[27]
Peela JR, Jarari AM, Hai A, et al. Cardiac biomarkers: The troponins and CK-MB. Ibnosina J Med Biomed Sci 2010; 2(5) Available from: https://www.academia.edu/32760206/Cardiac_BioMarkers_The_Troponins_and_CK_MB
[28]
Hsu CH, Chi BC, Casida JE. Melatonin reduces phosphine-induced lipid and DNA oxidation in vitro and in vivo in rat brain. J Pineal Res 2002; 32(1): 53-8.
[http://dx.doi.org/10.1034/j.1600-079x.2002.10809.x] [PMID: 11841601]
[29]
Shadnia S, Soltaninejad K, Hassan ian-Moghadam H, et al. Methemoglobinemia in aluminum phosphide poisoning. Hum Exp Toxicol 2011; 30(3): 250-3.
[http://dx.doi.org/10.1177/0960327110384287] [PMID: 20889582]
[30]
Moseley R, Stewart JE, Stephens P, Waddington RJ, Thomas DW. Extracellular matrix metabolites as potential biomarkers of disease activity in wound fluid: Lessons learned from other inflammatory diseases? Br J Dermatol 2004; 150(3): 401-13.
[http://dx.doi.org/10.1111/j.1365-2133.2004.05845.x] [PMID: 15030321]
[31]
Kariman H, Heydari K, Fakhri M, et al. Aluminium phosphide poisoning and oxidative stress: Serum biomarker assessment. J Med Toxicol 2012; 8(3): 281-4.
[http://dx.doi.org/10.1007/s13181-012-0219-1] [PMID: 22407514]
[32]
Etemad L, Montazeri D, Moshiri M, Jaafari MR, Arabzadeh S, Karimi G. Protective effects of nanomicelle curcumin on the phosphine-induced oxidative stress and apoptosis in human liver HepG2 cells. Nanomed J 2022; 9(2)
[33]
Haghi Aminjan H, Abtahi SR, Hazrati E, Chamanara M, Jalili M, Paknejad B. Targeting of oxidative stress and inflammation through ROS/NF-kappaB pathway in phosphine-induced hepatotoxicity mitigation. Life Sci 2019; 232: 116607.
[http://dx.doi.org/10.1016/j.lfs.2019.116607] [PMID: 31254582]
[34]
Anand R, Binukumar BK, Gill KD. Aluminum phosphide poisoning: An unsolved riddle. J Appl Toxicol 2011; 31(6): 499-505.
[http://dx.doi.org/10.1002/jat.1692] [PMID: 21607993]
[35]
Rathore R, Khan MZU. Morbidity, mortality and management of wheat pill poisoning. J Services Inst Med Sci 2007; 2: 14-28.
[36]
Soltaninejad K, Beyranvand MR, Momenzadeh SA, Shadnia S. Electrocardiographic findings and cardiac manifestations in acute aluminum phosphide poisoning. J Forensic Leg Med 2012; 19(5): 291-3.
[http://dx.doi.org/10.1016/j.jflm.2012.02.005] [PMID: 22687771]
[37]
Zniber K. Reversible myocardial injury associated with aluminum phosphide poisoning: Case report. Sch J Med Case Rep 2021; 5: 476-9.
[38]
Aziz U, Husain A. Frequency of cardiac arrhythmias in patients with aluminum phosphide poisoning. Asia Pac J Med Toxicol 2015; 4: 147-50.
[39]
Saleki S, Ardalan FA, Javidan-Nejad A. Liver histopathology of fatal phosphine poisoning. Forensic Sci Int 2007; 166(2-3): 190-3.
[http://dx.doi.org/10.1016/j.forsciint.2006.05.033] [PMID: 16806774]
[40]
Shah V, Baxi S, Vyas T. Severe myocardial depression in a patient with aluminium phosphide poisoning: A clinical, electrocardiographical and histopathological correlation. Indian J Crit Care Med 2009; 13(1): 41-3.
[http://dx.doi.org/10.4103/0972-5229.53117]
[41]
Tahergorabi Z, Zardast M, Naghizadeh A, Mansouri B, Nakhaei I, Zangouei M. Effect of aluminium phosphide (ALP) gas inhalation exposure on adipose tissue characteristics and histological toxicity in male rats. J Taibah Univ Sci 2020; 14(1): 1317-25.
[http://dx.doi.org/10.1080/16583655.2020.1820155]
[42]
Moalin M, Strijdonck GPF, Beckers M, et al. A planar conformation and the hydroxyl groups in the B and C rings play a pivotal role in the antioxidant capacity of quercetin and quercetin derivatives. Molecules 2011; 16(11): 9636-50.
[http://dx.doi.org/10.3390/molecules16119636] [PMID: 22105713]
[43]
Battelli MG, Polito L, Bortolotti M, Bolognesi A. Xanthine oxidoreductase-derived reactive species: Physiological and pathological effects. Oxid Med Cell Longev 2016; 2016: 1-8.
[http://dx.doi.org/10.1155/2016/3527579] [PMID: 26823950]
[44]
Boesch-Saadatmandi C, Loboda A, Wagner AE, et al. Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: Role of miR-155. J Nutr Biochem 2011; 22(3): 293-9.
[http://dx.doi.org/10.1016/j.jnutbio.2010.02.008] [PMID: 20579867]
[45]
Myhrstad MCW, Carlsen H, Nordström O, Blomhoff R, Moskaug JØ. Flavonoids increase the intracellular glutathione level by transactivation of the γ-glutamylcysteine synthetase catalytical subunit promoter. Free Radic Biol Med 2002; 32(5): 386-93.
[http://dx.doi.org/10.1016/S0891-5849(01)00812-7] [PMID: 11864778]
[46]
Meyers KJ, Rudolf JL, Mitchell AE. Influence of dietary quercetin on glutathione redox status in mice. J Agric Food Chem 2008; 56(3): 830-6.
[http://dx.doi.org/10.1021/jf072358l] [PMID: 18198829]
[47]
Eftekhari A, Ahmadian E, Panahi-Azar V, Hosseini H, Tabibiazar M, Maleki Dizaj S. Hepatoprotective and free radical scavenging actions of quercetin nanoparticles on aflatoxin B1-induced liver damage: In vitro/in vivo studies. Artif Cells Nanomed Biotechnol 2018; 46(2): 411-20.
[http://dx.doi.org/10.1080/21691401.2017.1315427] [PMID: 28423950]
[48]
Sadik CD, Sies H, Schewe T. Inhibition of 15-lipoxygenases by flavonoids: Structure-activity relations and mode of action. Biochem Pharmacol 2003; 65(5): 773-81.
[http://dx.doi.org/10.1016/S0006-2952(02)01621-0] [PMID: 12628491]
[49]
Li T, Li F, Liu X, Liu J, Li D. Synergistic anti-inflammatory effects of quercetin and catechin via inhibiting activation of TLR4-MyD88-mediated NF-κB and MAPK signaling pathways. Phytother Res 2019; 33(3): 756-67.
[http://dx.doi.org/10.1002/ptr.6268] [PMID: 30637814]