Therapeutic Potential of Curcuma longa Rhizome Solvent Fractions Against Benz[a]Anthracene-induced Pulmonary Toxicity: In vivo Insights

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Authors

  • Department of Veterinary Pharmacology and Toxicology, University of Agriculture, Makurdi. P. M. B. 2373 Makurdi, Benue ,NG
  • Department of Veterinary Pharmacology and Toxicology, University of Agriculture, Makurdi. P. M. B. 2373 Makurdi, Benue ,NG
  • Department of Veterinary Pharmacology and Toxicology, University of Agriculture, Makurdi. P. M. B. 2373 Makurdi, Benue ,NG
  • Del Scan Services Limited. 12th, 7th Avenue off Inikpi Street, High Level, 970001 Makurdi, Benue State ,NG
  • Department of Veterinary Pharmacology and Toxicology, University of Agriculture, Makurdi. P. M. B. 2373 Makurdi, Benue ,NG
  • Department of Veterinary Pharmacology and Toxicology, University of Agriculture, Makurdi. P. M. B. 2373 Makurdi, Benue ,NG
  • Department of Veterinary Pharmacology and Toxicology, University of Agriculture, Makurdi. P. M. B. 2373 Makurdi, Benue ,NG

DOI:

https://doi.org/10.18311/ti/2024/v31i3/43658

Keywords:

Benz[a]anthracene, Curcuma longa, Histopathology Scoring, Pulmonary Toxicity, Rats potential

Abstract

Benz[a]anthracene, a polycyclic aromatic hydrocarbon found in environmental pollutants, poses significant health risks, particularly to the respiratory system. This study aimed to evaluate the potential therapeutic effects of different solvent fractions of Curcuma longa rhizome methanol extracts against benz[a]anthracene-induced pulmonary toxicity using an in vivo rat model. The methanol crude extract of C. longa was partially fractionated using partition chromatography with silica gel as the adsorbent. Four solvent fractions obtained using gradient elution (designated ethanol, ethyl acetate, diethyl ether, and n-hexane fractions) were collected and used in the experiment. Albino Wistar rats (Rattus norvegicus) were randomly divided into seven groups and administered benz[a]anthracene to induce pulmonary toxicity. Subsequently, rats were treated with different solvent fractions of C. longa or diclofenac sodium as a positive control. Body weights were measured weekly, pre-induction, post-induction and post-treatment blood samples were collected, and lung tissue samples were collected and analysed. Treatment with the ethyl acetate fraction of C. longa resulted in significant improvements in lung histopathology compared to benz[a]anthracene-treated rats alone, suggesting potential anti-inflammatory effects. Furthermore, this fraction showed significant antioxidant enzyme activities, including glutathione peroxidase, glutathione reductase, and superoxide dismutase, indicating its ability to mitigate oxidative stress. Biochemical analysis revealed that the ethyl acetate fraction also significantly decreased serum levels of tumour biomarkers, such as epidermal growth factor receptor, cancer antigen 125, and carcinoembryonic antigen, suggesting its potential in inhibiting cancer-related processes induced by benz[a]anthracene exposure. Our findings suggest that the ethyl acetate fraction of C. longa rhizome may hold promise as a therapeutic agent against benz[a]anthracene-induced pulmonary toxicity, possibly through its anti-inflammatory, antioxidant, and anticancer properties. Further research is warranted to elucidate the specific compounds present in this fraction and the underlying mechanisms through which they exert their effects, to optimize their therapeutic potential.

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Published

2024-08-05

How to Cite

Oluchi, O. M., Chukwuebuka, N. H., Ieren, I. I., Fatai, O. B., Joel, B. A., Saganuwan, S. A., & Azubuike, O. P. (2024). Therapeutic Potential of <i>Curcuma longa</i> Rhizome Solvent Fractions Against Benz[a]Anthracene-induced Pulmonary Toxicity: <i>In vivo</i> Insights. Toxicology International, 31(3), 489–513. https://doi.org/10.18311/ti/2024/v31i3/43658
Received 2024-04-17
Accepted 2024-06-25
Published 2024-08-05

 

References

Agilent Technologies. Material Safety Data Sheet: Benz[a]anthracene. Available from: [https://www.agilent.com/cs/library/msds/P-640-1_NAEnglish.pdf](https://www.agilent.com/cs/library/msds/P-640-1_NAEnglish.pdf)

Talhout R, Schulz T, Florek E, Van Benthem J, Wester P, Opperhuizen A. Hazardous compounds in tobacco smoke. Int J Environ Res Public Health. 2011;8(2):613-628. DOI: https://doi.org/10.3390/ijerph8020613

Gray JP, Hall GJ. Benz [a] anthracene. In: Wexler P, ed. Encyclopedia of Toxicology: Third Edition. Academic Press; 2014:413-414. DOI: https://doi.org/10.1016/B978-0-12-386454-3.00247-5

Wallig MA, Bolon B, Haschek WM, Rousseaux CG, eds. Fundamentals of toxicologic pathology. 2nd ed. Academic Press; 2017:93-133.

Oluchi OM, Chukwuebuka NH, Orbunde DK, Saganuwan SA, Azubuike OP. Evaluation of Benz [A] anthracene-induced pulmonary toxicity in Rattus norvegicus.

Yue GG, Chan BC, Hon PM, Lee MY, Fung KP, Leung PC, Lau CB. Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from C. longa. Food Chem Toxicol. 2010;48(8-9):2011-2020. DOI: https://doi.org/10.1016/j.fct.2010.04.039

Mathai NJ, Sony D, Mane PP, Shetty CB, Latheef L, Kamath K, Kochikuzhyil BM, Baliga MS. Antiarthritic effects of turmeric and curcumin: A revisit. In: Watson RR, Preedy VR, eds. Polyphenols: Prevention and Treatment of Human Disease. Academic Press; 2018:247-252. DOI: https://doi.org/10.1016/B978-0-12-813008-7.00020-5

Chanda S, Ramachandra TV. Phytochemical and pharmacological importance of turmeric (C. longa): A review. Res Rev: J Pharmacol. 2019;9(1):16-23.

Liju VB, Jeena K, Kuttan R. An evaluation of antioxidant, anti-inflammatory, and antinociceptive activities of essential oil from C. longa L. Indian J Pharmacol. 2011;43(5):526-531. DOI: https://doi.org/10.4103/0253-7613.84961

Kumar N, Pruthi V. Potential applications of ferulic acid from natural sources. Biotechnol Rep. 2014;4:86-93. DOI: https://doi.org/10.1016/j.btre.2014.09.002

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):9183-9213. DOI: https://doi.org/10.3390/molecules20059183

Jyotirmayee B, Mahalik G. A review on selected pharmacological activities of C. longa L. Int J Food Prop. 2022;25(1):1377-1398. DOI: https://doi.org/10.1080/10942912.2022.2082464

Malwade CR, Qu H, Rong BG, Christensen LP. Chemometrics for analytical data mining in separation process design for recovery of artemisinin from Artemisia annua. Ind Eng Chem Res. 2014;53(13):5582-5589. DOI: https://doi.org/10.1021/ie404233z

Council for International Organizations of Medical Sciences (C.I.O.M.S). International guiding principles for biomedical research involving animals. Altern Lab Anim. 1985;12:ii.

Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals. J Pharmacol Pharmacother. 2010;1(2):87. DOI: https://doi.org/10.4103/0976-500X.72350

Cheesbrough M. District Laboratory Practice in Tropical Countries. Part 1. 2nd ed.

Wayne PA. Procedure for Determining Packed Cell Volume by the Microhematocrit Method; Approved Standard—Third Edition. Document H07-A3. 2000.

Pal GK. Textbook Of Practical Physiology-2Nd Edn. Orient Blackswan; 2006.

Wayne PA. Reference leukocyte (WBC) differential count (proportional) and evaluation of instrument methods: approved standard. Document H20-A2. 2007.

Chabot-Richards DS, George TI. White blood cell counts: reference methodology. Clin Lab Med. 2015;35(1):11-24. DOI: https://doi.org/10.1016/j.cll.2014.10.007

Underwood W, Anthony R. AVMA guidelines for the euthanasia of animals: 2020 edition. Retrieved on March, 2013(30), 2020-1.

Simpson RJ. Homogenization of mammalian tissue. Cold Spring Harbor Protoc. 2010;2010(7):pdb-prot5455. DOI: https://doi.org/10.1101/pdb.prot5455

Jollow DJ, Mitchell JR, Zampaglione NA, Gillette JR. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology. 1974;11(3):151-169. DOI: https://doi.org/10.1159/000136485

Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249(22):7130-7139. DOI: https://doi.org/10.1016/S0021-9258(19)42083-8

Carlberg I, Mannervik B. Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem. 1975;250(14):5475-5480. DOI: https://doi.org/10.1016/S0021-9258(19)41206-4

Mohandas J, Marshall JJ, Duggin GG, Horvath JS, Tiller DJ. Differential distribution of glutathione and glutathione-related enzymes in rabbit kidney: possible implications in analgesic nephropathy. Biochem Pharmacol. 1984;33(11):1801-180 DOI: https://doi.org/10.1016/0006-2952(84)90353-8

Clairbone A. Catalase activity. In: Handbook of methods for oxygen radical research. Boca Raton (FL): CRC Press; 1985. p. 283-284.

Beauchamp C, Fridovich I. Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem. 1971;44(1):276-287. DOI: https://doi.org/10.1016/0003-2697(71)90370-8

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72(1-2):248-254. DOI: https://doi.org/10.1006/abio.1976.9999

Drury RA, Wellington EA. Carlton’s Histo-pathological Techniques. Oxford: Oxford University Press; 1976.

Holland T, Holland C. Analysis of unbiased histopathology data from rodent toxicity studies (or, are these groups different enough to ascribe it to treatment?). Toxicol Pathol. 2011;39(4):569-575. DOI: https://doi.org/10.1177/0192623311406289

Ashcroft T, Simpson JM, Timbrell V. Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol. 1988;41(4):467-470. DOI: https://doi.org/10.1136/jcp.41.4.467

Hübner RH, Gitter W, Eddine El Mokhtari N, Mathiak M, Both M, Bolte H, et al. Standardized quantification of pulmonary fibrosis in histological samples. Biotechniques. 2008;44(4):507-517. DOI: https://doi.org/10.2144/000112729

Kubiak BD, Albert SP, Gatto LA, Snyder KP, Maier KG, Vieau CJ, et al. Peritoneal negative pressure therapy prevents multiple organ injury in a chronic porcine sepsis and ischemia/reperfusion model. Shock. 2010;34(5):525-534. DOI: https://doi.org/10.1097/SHK.0b013e3181e14cd2

Silva IAN, Gvazava N, Bölükbas DA, Stenlo M, Dong J, Hyllen S, et al. A Semi-quantitative Scoring System for Green Histopathological Evaluation of Large Animal Models of Acute Lung Injury. Bio-protocol. 2022;12(16):e4493. https://doi.org/10.21769/BioProtoc.4493 DOI: https://doi.org/10.21769/BioProtoc.4493

Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: what are its features and how important is it? Thorax. 2009;64(8):728-735. DOI: https://doi.org/10.1136/thx.2008.108027

GraphPad Software Inc, La Jolla, CA, USA.

Ngo TV, Scarlett CJ, Bowyer MC, Ngo PD, Vuong QV. Impact of different extraction solvents on bioactive compounds and antioxidant capacity from the root of Salacia chinensis L. J Food Qual. 2017. DOI: https://doi.org/10.1155/2017/9305047

Ibrahim HAH. Introductory Chapter: Fractionation. In: Fractionation. IntechOpen; 2018.

Stéphane FFY, Jules BKJ, Batiha GE, Ali I, Bruno LN. Extraction of bioactive compounds from medicinal plants and herbs. Nat Med Plants. 2021.

Arawande JO, Akinnusotu A, Alademeyin JO. Extractive value and phytochemical screening of ginger (Zingiber officinale) and turmeric (C. longa) using different solvents. Int J Trad Nat Med. 2018;8(1):13-22.

Cui Z, Yao L, Ye J, Wang Z, Hu Y. Solubility measurement and thermodynamic modelling of curcumin in twelve pure solvents and three binary solvents at different temperature (T= 278.15–323.15 K). J Mol Liquids. 2021;338:116795. DOI: https://doi.org/10.1016/j.molliq.2021.116795

Pant P, Pandey S, Dall'Acqua S. The Influence of Environmental Conditions on Secondary Metabolites in Medicinal Plants: A Literature Review. Chem Biodivers. 2021;18(11):e2100345. https://doi.org/10.1002/cbdv.202100345 DOI: https://doi.org/10.1002/cbdv.202100345

Zhang QW, Lin LG, Ye WC. Techniques for extraction and isolation of natural products: A comprehensive review. Chin Med. 2018;13:1-26. DOI: https://doi.org/10.1186/s13020-018-0177-x

Abubakar AR, Haque M. Preparation of medicinal plants: Basic extraction and fractionation procedures for experimental purposes. J Pharm Bioallied Sci. 2020;12(1):1. DOI: https://doi.org/10.4103/jpbs.JPBS_175_19

Yuan H, Ma Q, Ye L, Piao G. The Traditional Medicine and Modern Medicine from Natural Products. Molecules. 2016;21(5):559. https://doi.org/10.3390/molecules21050559 DOI: https://doi.org/10.3390/molecules21050559

Nasim N, Sandeep IS, Mohanty S. Plant-derived natural products for drug discovery: Current approaches and prospects. Nucleus. 2022;65(3):399-411. DOI: https://doi.org/10.1007/s13237-022-00405-3

van Berlo D, Woutersen M, Muller A, Pronk M, Vriend J, Hakkert B. 10% Body weight (gain) change as criterion for the maximum tolerated dose: A critical analysis. Regul Toxicol Pharmacol. 2022;134:105235. DOI: https://doi.org/10.1016/j.yrtph.2022.105235

Cederholm T, Barazzoni R, Austin P, Ballmer P, Biolo GIANNI, Bischoff SC, et al. ESPEN guidelines on definitions and terminology of clinical nutrition. Clin Nutr. 2017;36(1):49-64. DOI: https://doi.org/10.1016/j.clnu.2016.09.004

Piao Y, Liu Y, Xie X. Change trends of organ weight background data in sprague dawley rats at different ages. J Toxicol Pathol. 2013;26(1):29-34. DOI: https://doi.org/10.1293/tox.26.29

Silva AV, Norinder U, Liiv E, Platzack B, Öberg M, Törnqvist E. Associations between clinical signs and pathological findings in toxicity testing. ALTEX. 2021;38(2):198–214. doi: 10.14573/altex.2003311. DOI: https://doi.org/10.14573/altex.2003311

Moldoveanu B, Otmishi P, Jani P, Walker J, Sarmiento X, Guardiola J, et al. Inflammatory mechanisms in the lung. J Inflamm Res. 2009;2:1–11.

Elshama SS, El-Kenawy AEM, Osman HEH. Histopathological study of cyclosporine pulmonary toxicity in rats. J Toxicol. 2016;2016. DOI: https://doi.org/10.1155/2016/2973274

Ranieri VITO, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute respiratory distress syndrome: the Berlin Definition. Jama. 2012;307(23):2526-2533. DOI: https://doi.org/10.1001/jama.2012.5669

Aulbach AD, Amuzie CJ. Biomarkers in nonclinical drug development. In: A comprehensive guide to toxicology in nonclinical drug development. Academic Press; 2017. p. 447-471. DOI: https://doi.org/10.1016/B978-0-12-803620-4.00017-7

Hussan F, Mansor AS, Hassan SN, Kamaruddin TNE, Tasnim TN, Budin SB, et al. Anti-inflammatory property of Plantago major leaf extract reduces the inflammatory reaction in experimental acetaminophen-induced liver injury. Evid Based Complement Alternat Med. 2015. DOI: https://doi.org/10.1155/2015/347861

Peng J. The pharmacological targets and clinical evidence of natural products with anti-hepatic inflammatory properties. Front Pharmacol. 2018;9:455. DOI: https://doi.org/10.3389/fphar.2018.00455

Jacob Filho W, Lima CC, Paunksnis MRR, Silva AA, Perilhão MS, Caldeira M, et al. Reference database of hematological parameters for growing and aging rats. Aging Male. 2018;21(2):145-148. DOI: https://doi.org/10.1080/13685538.2017.1350156

Lowe D, Sanvictores T, Zubair M, John S. Alkaline phosphatase. StatPearls. 2023.

Lala V, Zubair M, Minter D. Liver function tests. StatPearls. 2023.

Gregus Z, Klaassen CD. Mechanisms of toxicity. The basic science of poisons. 5th ed. New York: McGraw-Hill; 2001. p. 35-74.

Everds NE, Snyder PW, Bailey KL, Bolon B, Creasy DM, Foley GL, et al. Interpreting stress responses during routine toxicity studies: a review of the biology, impact, and assessment. Toxicol Pathol. 2013;41(4):560-614. DOI: https://doi.org/10.1177/0192623312466452

Higgins C. Urea and creatinine concentration, the urea: creatinine ratio. Acute Care Test Hand. 2016:1-8.

Gounden V, Bhatt H, Jialal I. Renal function tests.

Catanzaro M, Corsini E, Rosini M, Racchi M, Lanni C. Immunomodulators inspired by nature: a review on curcumin and echinacea. Molecules. 2018;23(11):2778. DOI: https://doi.org/10.3390/molecules23112778

Yuandani, Jantan I, Rohani AS, Sumantri IB. Immunomodulatory effects and mechanisms of curcuma species and their bioactive compounds: A review. Front Pharmacol. 2021;12:643119. DOI: https://doi.org/10.3389/fphar.2021.643119

Behl T, Kumar K, Brisc C, Rus M, Nistor-Cseppento DC, Bustea C, et al. Exploring the multifocal role of phytochemicals as immunomodulators. Biomed Pharmacother. 2021;133:110959. DOI: https://doi.org/10.1016/j.biopha.2020.110959

Morell AR. CEA serum levels in non-neoplastic disease. Int J Biol Markers. 1992;7(3):160-166. DOI: https://doi.org/10.1177/172460089200700307

Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol. 2018;12(1):3-20. DOI: https://doi.org/10.1002/1878-0261.12155

Andhi T, Zubair M, Bhatt H. Cancer Antigen 125. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan 18-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562245/

Kankanala VL, Mukkamalla SKR. Carcinoembryonic Antigen. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan 23-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK578172/

Pujol JL, Grenier J, Daurès JP, Daver A, Pujol H, Michel FB. Serum fragment of cytokeratin subunit 19 measured by CYFRA 21-1 immunoradiometric assay as a marker of lung cancer. Cancer Res. 1993;53(1):61-66.

Stieber P, Hasholzner U, Bodenmüller H, Nagel D, Sunder‐Plassmann L, Dienemann H, et al. CYFRA 21‐1: a new marker in lung cancer. Cancer. 1993;72(3):707-713. DOI: https://doi.org/10.1002/1097-0142(19930801)72:3<707::AID-CNCR2820720313>3.0.CO;2-X

Wieskopf B, Demangeat C, Purohit A, Stenger R, Gries P, Kreisman H, et al. Cyfra 21-1 as a biologic marker of non-small cell lung cancer: evaluation of sensitivity, specificity, and prognostic role. Chest. 1995;108(1):163-169. DOI: https://doi.org/10.1378/chest.108.1.163

Agency for Toxic Substances and Disease Registry. Toxicological profile for polycyclic aromatic hydrocarbons. Atlanta, GA: ATSDR; 1995.

Mumtaz MM, George JD, Gold KW, Cibulas W, DeRosa CT. ATSDR evaluation of health effects of chemicals. IV. Polycyclic aromatic hydrocarbons (PAHs): understanding a complex problem. Toxicol Ind Health. 1996;12(6):742-971. DOI: https://doi.org/10.1177/074823379601200601

Sevinc A, Adli M, Kalender ME, Camci C. Benign causes of increased serum CA-125 concentration. Lancet Oncol. 2007;8(12):1054-1055. DOI: https://doi.org/10.1016/S1470-2045(07)70357-1

Johnson CC, Kessel B, Riley TL, Ragard LR, Williams CR, Xu JL, et al. The epidemiology of CA-125 in women without evidence of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial. Gynecol Oncol. 2008;110(3):383-389. DOI: https://doi.org/10.1016/j.ygyno.2008.05.006

Sang GY, Chen ZY, Meng CR, Tian T, Zhang ZX. Serum tumor marker carbohydrate antigen 125 levels and carotid atherosclerosis in patients with coronary artery disease. Open Medicine. 2018;13(1):534-538. DOI: https://doi.org/10.1515/med-2018-0078

Bardelčíková A, Šoltys J, Mojžiš J. Oxidative Stress, Inflammation and Colorectal Cancer: An Overview. Antioxidants. 2023;12(4):901. DOI: https://doi.org/10.3390/antiox12040901

Fukuda I, Yamakado M, Kiyose H. Influence of smoking on serum carcinoembryonic antigen levels in subjects who underwent multiphasic health testing and services. J Med Syst. 1998;22(2):89-93. DOI: https://doi.org/10.1023/A:1022643102208

Thomas P, Forse RA, Bajenova O. Carcinoembryonic antigen (CEA) and its receptor hnRNP M are mediators of metastasis and the inflammatory response in the liver. Clin Exp Metastasis. 2011;28:923-932. DOI: https://doi.org/10.1007/s10585-011-9419-3

Rizeq B, Zakaria Z, Ouhtit A. Towards understanding the mechanisms of actions of carcinoembryonic antigen‐related cell adhesion molecule 6 in cancer progression. Cancer Sci. 2018;109(1):33-42. DOI: https://doi.org/10.1111/cas.13437

Kwon YJ, Lee HS, Shim JY, Lee YJ. Serum carcinoembryonic antigen is positively associated with leukocyte count in Korean adults. J Clin Lab Anal. 2018;32(3):e22291. DOI: https://doi.org/10.1002/jcla.22291

Hodges RE, Minich DM. Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application. J Nutr Metab. 2015;2015:760689. DOI: https://doi.org/10.1155/2015/760689

Lee JH, Lee SW. The roles of carcinoembryonic antigen in liver metastasis and therapeutic approaches. Gastroenterol Res Pract. 2017;2017. DOI: https://doi.org/10.1155/2017/7521987

Li Y, Cao H, Jiao Z, Pakala SB, Sirigiri DNR, Li W, et al. Carcinoembryonic antigen interacts with TGF-β receptor and inhibits TGF-β signaling in colorectal cancers. Cancer Res. 2010;70(20):8159-8168. DOI: https://doi.org/10.1158/0008-5472.CAN-10-1073

Huang R, Meng T, Zha Q, Cheng K, Zhou X, Zheng J, et al. The predicting roles of carcinoembryonic antigen and its underlying mechanism in the progression of coronavirus disease 2019. Crit Care. 2021;25(1):1-20. DOI: https://doi.org/10.1186/s13054-021-03661-y

Sharma R, Yang Y, Sharma A, Awasthi S, Awasthi YC. Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxid Redox Signal. 2004;6(2):289-300. DOI: https://doi.org/10.1089/152308604322899350

Allocati N, Masulli M, Di Ilio C, Federici L. Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases. Oncogenesis. 2018;7(1):8. DOI: https://doi.org/10.1038/s41389-017-0025-3

Chaudhary P, Janmeda P, Docea AO, Yeskaliyeva B, Abdull Razis AF, Modu B, et al. Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Front Chem. 2023;11:1158198. DOI: https://doi.org/10.3389/fchem.2023.1158198

Alrawaiq NS, Abdullah A. A review of antioxidant polyphenol curcumin and its role in detoxification. Int J Pharm Tech Res. 2014;6(1):280-289.

Fuloria S, Mehta J, Chandel A, Sekar M, Rani NNIM, Begum MY, et al. A comprehensive review on the therapeutic potential of C. longa Linn. in relation to its major active constituent curcumin. Front Pharmacol. 2022;13:820806. DOI: https://doi.org/10.3389/fphar.2022.820806

Lubos E, Loscalzo J, Handy DE. Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities.

Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012;5(1):9–19. DOI: https://doi.org/10.1097/WOX.0b013e3182439613

Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J Med. 2018;54(4):287-293. DOI: https://doi.org/10.1016/j.ajme.2017.09.001

Sarıkaya E, Doğan S. Glutathione peroxidase in health and diseases. In: Glutathione system and oxidative stress in health and disease; 2020. DOI: https://doi.org/10.5772/intechopen.91009

Demirci-Cekic S, Özkan G, Avan AN, Uzunboy S, Çapanoğlu E, Apak R. Biomarkers of oxidative stress and antioxidant defense. J Pharm Biomed Anal. 2022;209:114477. DOI: https://doi.org/10.1016/j.jpba.2021.114477

Eteng O, Moses CA, Enobong J, Akamo AJ, Akinloye DI, Ugbaja RN, et al. Protective effects of C. longa rhizomes ethyl acetate extract against alcohol induced oxidative stress and nephrotoxicity in female Wistar rats. Asian J Nat Prod Biochem. 2020;18(1). DOI: https://doi.org/10.13057/biofar/f180102

Auychaipornlert S, Lawanprasert PP, Piriyaprasarth S, Sithisarn P, Mangmool S. Design of turmeric rhizome extract nano-formula for delivery to cancer cells. Molecules. 2022;27(3):896. DOI: https://doi.org/10.3390/molecules27030896

Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic Biol Med. 2016;95:27-42. DOI: https://doi.org/10.1016/j.freeradbiomed.2016.02.028

Memarzia A, Khazdair MR, Behrouz S, Gholamnezhad Z, Jafarnezhad M, Saadat S, et al. Experimental and clinical reports on anti‐inflammatory, antioxidant, and immunomodulatory effects of C. longa and curcumin, an updated and comprehensive review. BioFactors. 2021;47(3):311-350. DOI: https://doi.org/10.1002/biof.1716

Bansal M, Poonia A, Kolluri SRP, Vasundhara. Introduction on Bioactive Compounds, Sources and their Potential Applications. In: Bansal M, Poonia A, Kolluri SRP, Vasundhara, editors. Bioactive Components: A Sustainable System for Good Health and Well-Being. Singapore: Springer Nature Singapore; 2022. p. 3-26. DOI: https://doi.org/10.1007/978-981-19-2366-1_1