EFFICIENCY OF CURCUMIN AND CHITOSAN NANOPARTICLES AGAINST TOXICITY OF POTASSIUM DICHROMATE IN MALE MICE
Objective: The purpose of this work is to examine the protective effect of nanocurcumin and nanochitosan supplementation against potassium dichromate toxicity in male mice.
Methods: Male albino mice weighing 25-30 gm were divided into six groups; the first group received saline. Second and third groups were given oral dose of nanocurcumin and nanochitosan respectively for 5 d. Fourth group was injected subcutaneously with a single dose of potassium dichromate for 24 h. Group five and six were administrated nanocurcumin and nanochitosan, respectively prior to potassium dichromate. Animals were anesthetized by ether anesthesia then bone marrow was harvested for chromosomal examination and epididymal sperms were collected for sperm morphology, while Kidneys and testes were collected for western blot and biochemical analysis.
Results: Potassium dichromate induced significant (P≤0.05) increase in chromosome and sperm abnormalities as well as testicular and renal MDA, renal MPO, renal contents of IL-18 and IGF-1, testicular contents of caspase 3 and cytosolic cytochrome c, a reduction in testosterone level, and GPx of renal and testicular tissues compared to control group. Pretreatment with both types of nanoparticles showed significant (P≤0.05) mitigation against most alterations induced by potassium dichromate; moreover, nanochitosan gave more significant (P≤0.05) improvement against chromosome and sperm abnormalities than nanocurcumin.
Conclusion: The present study revealed that the selected nanoparticles have antioxidant as well as antigenotoxic properties against toxicity of potassium dichromate.
2. Al Osman M, Yang F, Massey IY. Exposure routes and health effects of heavy metals on children. Biometals 2019;32:563-73.
3. Rahman Z, Singh VP. The relative impact of toxic heavy metals (THMs) (arsenic (As), cadmium (Cd), chromium (Cr)(VI), mercury (Hg), and lead (Pb)) on the total environment: an overview. Environ Monit Assess 2019;419:1-21.
4. Pavesi T, Moreira JC. Mechanisms and individuality in chromium toxicity in humans. J Appl Toxicol 2020;40:1183-97.
5. Chen H, Arocena JM, Li J, Thring RW, Zhou J. Mobility and storage sinks for chromium and other metals in soils impacted by leather tannery wastes. J Environ Monit 2012;14:3240-8.
6. Jaishankar M, Tseten T, Anbalagan N, Mathew BB, Beeregowda KN. Toxicity, mechanism and health effects of some heavy metals. Interdiscip Toxicol 2014;7:60-72.
7. Matern K, Mansfeldt T. Chromium release from a COPR-contaminated soil at varying water content and redox conditions. J Environ Qual 2016;45:1259-67.
8. Avila Rojas SH, Tapia E, Briones Herrera A, Aparicio Trejo OE, Leon Contreras JC, Hernandez Pando R, et al. Curcumin prevents potassium dichromate (K2Cr2O7)-induced renal hypoxia. Food Chem Toxicol 2018;121:472-82.
9. Mary Momo CM, Ferdinand N, Omer Bebe NK, Alexane Marquise MN, Augustave K, Bertin Narcisse V, et al. Oxidative effects of potassium dichromate on biochemical, hematological characteristics, and hormonal levels in rabbit doe (Oryctolagus cuniculus). Vet Sci 2019;6:1-13.
10. Rasool M, Zaigham K, Malik A, Naseer MI, Umm-E-Habiba, Manan A, et al. Potential reproductive health effects and oxidative stress associated with exposure to potassium dichromate (K2Cr2O7) and magnesium sulphate (MgSO4) in male mice. Pak J Med Sci 2014;30:819-23.
11. Marouani N, Tebourbi O, Hallegue D, Mokni M, Yacoubi MT, Sakly M, et al. Mechanisms of chromium hexavalent-induced apoptosis in rat testes. Toxicol Ind Health 2017;33:97-106.
12. Yoisungnern T, Das J, Choi YJ, Parnpai R, Kim JH. Effect of hexavalent chromium-treated sperm on in vitro fertilization and embryo development. Toxicol Ind Health 2016;32:1700-10.
13. Mamyrbaev AA, Dzharkenov TA, Imangazina ZA, Satybaldieva UA. Mutagenic and carcinogenic actions of chromium and its compounds. Environ Health Prev Med 2015;20:159-67.
14. Subramanian S, Rajendiran G, Sekhar P, Gowri C, Govindarajulu P, Aruldhas MM. Reproductive toxicity of chromium in adult bonnet monkeys (Macaca radiata geoffrey). Reversible oxidative stress in the semen. Toxicol Appl Pharmacol 2006;215:237-49.
15. Bosgelmez II, Guvendik G. N-Acetyl-L-Cysteine protects liver and kidney against chromium(vi)-induced oxidative stress in mice. Biol Trace Elem Res 2017;178:44-53.
16. Abu Zeid EH, Hussein MMA, Ali H. Ascorbic acid protects male rat brain from oral potassium dichromate-induced oxdative DNA damage and apoptotic changes: the expression patterns of caspase-3, P 53, Bax, and Bcl-2 genes. Environ Sci Pollut Res Int 2018;25:13056-66.
17. Li J, Zheng X, Ma X, Xu X, Du Y, Lv Q, et al. Melatonin protects against chromium(VI)-induced cardiac injury via activating the AMPK/Nrf2 pathway. J Inorg Biochem 2019;197:110698.
18. Dashti A, Soodi M, Amani N. Cr (VI) induced oxidative stress and toxicity in cultured cerebellar granule neurons at different stages of development and protective effect of rosmarinic acid. Environ Toxicol 2016;31:269-77.
19. Luo D, Xu Z, Hu X, Zhang F, Bian H, Li N, et al. URI prevents potassium dichromate-induced oxidative stress and cell death in gastric cancer cells. Am J Transl Res 2016;8:5399-409.
20. Mohamed HM, Abd El-Twab SM. Gallic acid attenuates chromium-induced thyroid dysfunction by modulating antioxidant status and inflammatory cytokines. Environ Toxicol Pharmacol 2016;48:225-36.
21. Xueting L, Rehman MU, Mehmood K, Huang S, Tian X, Wu X, et al. Ameliorative effects of nano-elemental selenium against hexavalent chromium-induced apoptosis in broiler liver. Environ Sci Pollut Res Int 2018;25:15609-15.
22. Wu YH, Lin JC, Wang TY, Lin TJ, Yen MC, Liu YH, et al. Hexavalent chromium intoxication induces intrinsic and extrinsic apoptosis in human renal cells. Mol Med Rep 2020;21:851-7.
23. Kumar P, Kumar R, Nagpure NS, Nautiyal P, Kushwaha B, Dabas A. Genotoxicity and antioxidant enzyme activity induced by hexavalent chromium in Cyprinus carpio after in vivo exposure. Drug Chem Toxicol 2013;36:451-60.
24. Rocha C, Cardoso P, Cunha L, Gomes C, Junior RR, Pinheiro RH, et al. Mutagenic effects of potassium dichromate as evaluated by means of animal and plant bioindicators. In Vivo 2015;29:729-35.
25. El-Demerdash FM, Jebur AB, Nasr HM, Hamid HM. Modulatory effect of Turnera diffusa against testicular toxicity induced by fenitrothion and/or hexavalent chromium in rats. Environ Toxicol 2019;34:330-9.
26. Hfaiedh M, Brahmi D, Zourgui MN, Zourgui L. Phytochemical analysis and nephroprotective effect of cactus (Opuntia ficus-indica) cladodes on sodium dichromate-induced kidney injury in rats. Appl Physiol Nutr Metab 2019;44:239-47.
27. Amalraj A, Pius A, Gopi S, Gopi S. Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives-a review. J Tradit Complement Med 2017;7:205-33.
28. Kocaadam B, Sanlier N. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Crit Rev Food Sci Nutr 2017;57:2889-95.
29. El-Maddawy ZK, El-Sayed YS. Comparative analysis of the protective effects of curcumin and N-acetyl cysteine against paracetamol-induced hepatic, renal, and testicular toxicity in Wistar rats. Environ Sci Pollut Res Int 2018;25:3468-79.
30. Cao L, Zhi D, Han J, Kumar Sah S, Xie Y. Combinational effect of curcumin and metformin against gentamicin-induced nephrotoxicity: involvement of antioxidative, anti-inflammatory and antiapoptotic pathway. J Food Biochem 2019;43:1-9.
31. Aslanturk A, Uzunhisarcikli M. Protective potential of curcumin or taurine on nephrotoxicity caused by bisphenol A. Environ Sci Pollut Res Int 2020;27:23994-4003.
32. Zhang J, Tang L, Li G Sen, Wang J. The anti-inflammatory effects of curcumin on renal ischemia-reperfusion injury in rats. Ren Fail 2018;40:680-6.
33. Samarghandian S, Azimi Nezhad M, Farkhondeh T, Samini F. Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney. Biomed Pharmacother 2017;87:223-9.
34. Belhan S, Yildirim S, Huyut Z, Ozdek U, Oto G, Algul S. Effects of curcumin on sperm quality, lipid profile, antioxidant activity and histopathological changes in streptozotocin-induced diabetes in rats. Andrologia 2020;52:1-8.
35. Tomeh MA, Hadianamrei R, Zhao X. A review of curcumin and its derivatives as anticancer agents. Int J Mol Sci 2019;27;20:1-26.
36. Pan MH, Huang TM, Lin JK. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos 1999;27:486-94.
37. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm 2007;4:807-18.
38. Dei Cas M, Ghidoni R. Dietary curcumin: correlation between bioavailability and health potential. Nutrients 2019;11:1-14.
39. Das RK, Kasoju N, Bora U. Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomedicine 2010;6:153-60.
40. Gera M, Sharma N, Ghosh M, Huynh DL, Lee SJ, Min T, et al. Nanoformulations of curcumin: an emerging paradigm for improved remedial application. Oncotarget 2017;8:66680-98.
41. Hadidi M, Pouramin S, Adinepour F, Haghani S, Jafari SM. Chitosan nanoparticles loaded with clove essential oil: characterization, antioxidant and antibacterial activities. Carbohyd Polym 2020;236:116075.
42. Kravanja G, Primozic M, Knez Z, Leitgeb M. Chitosan-based (nano)materials for novel biomedical applications. Molecules 2019;24:1-23.
43. Bai K, Hong B, He J, Huang W. Antioxidant capacity and hepatoprotective role of chitosan-stabilized selenium nanoparticles in concanavalin a-induced liver injury in mice. Nutrients 2020;12;1-16.
44. Darwesh OM, Sultan YY, Seif MM, Marrez DA. Bio-evaluation of crustacean and fungal nano-chitosan for applying as a food ingredient. Toxicol Rep 2018;5:348-56.
45. Elchinger PH, Delattre C, Faure S, Roy O, Badel S, Bernardi T, et al. Antioxidant activities of peptoid-grafted chitosan films. Appl Biochem Biotechnol 2017;181:283-93.
46. Ivanova DG, Yaneva ZL. Antioxidant properties and redox-modulating activity of chitosan and its derivatives: biomaterials with application in cancer therapy. BioRes Open Access 2020;9:64-72.
47. Chang SH, Wu CH, Tsai GJ. Effects of chitosan molecular weight on its antioxidant and antimutagenic properties. Carbohyd Polym 2018;181:1026-32.
48. Lee DW, Shirley SA, Lockey RF, Mohapatra SS. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline. Respir Res 2006;7:1-10.
49. Dragostin OM, Tatia R, Samal SK, Oancea A, Zamfir AS, Dragostin I, et al. Designing of chitosan derivatives nanoparticles with antiangiogenic effect for cancer therapy. Nanomaterials 2020;10:1-19.
50. Abd El-Rahman SN, Al-Jameel SS. Protection of curcumin and curcumin nanoparticles against cisplatin induced nephrotoxicity in male rats. SAJB 2014;2:214-23.
51. Hegazy R, Salama A, Mansour D, Hassan A. Renoprotective effect of lactoferrin against chromium-induced acute kidney injury in rats: involvement of il-18 and igf-1 inhibition. PLoS One 2016;11:1-18.
52. Preston RJ, Dean BJ, Galloway S, Holden H, McFee AF, Shelby M. Mammalian in vivo cytogenetic assays. Analysis of chromosome aberrations in bone marrow cells. Mutat Res 1987;189:157-65.
53. Wyrobek AJ, Bruce WR. Chemical induction of sperm abnormalities in mice. Proc Natl Acad Sci USA 1975;72:4425-9.
54. 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;72:248-54.
55. Guo CH, Huang CJ, Chen ST, Wang Hsu GS. Serum and testicular testosterone and nitric oxide products in aluminum-treated mice. Environ Toxicol Pharmacol 2001;10:53-60.
56. Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978;86:271-8.
57. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158-69.
58. Hillegass LM, Griswold DE, Brickson B, Albrightson Winslow C. Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods 1990;24:285-95.
59. Burnette WN. “Western blotting”: electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem 1981;112:195-203.
60. Sambrook J, Fritsch EF, Maniatis T. Textbook of molecular cloning: a laboratory manual. 2nd Ed. Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY USA; 1989.
61. Yadav A, Kushwaha P, Flora SJS. Nanocurcumin prevents oxidative stress-induced following arsenic and fluoride co-exposure in rats. Def Life Sci J 2016;1:69-77.
62. Elmi T, Esboei BR, Sadeghi F, Zamani Z, Didehdar M, Fakhar M, et al. In vitro antiprotozoal effects of nano chitosan on Plasmodium falciparum,Ggiardia lamblia and Trichomonas vaginalis. Acta Parasitol 2020. https://doi.org/10.1007/ s11686-020-00255-6.
63. Flora G, Gupta D, Tiwari A. Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug 2013;30:331-68.
64. Zou P, Zhang J, Xia Y, Kanchana K, Guo G, Chen W, et al. ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer. Oncotarget 2015;6:5860-76.
65. Karthikeyan A, Senthil N, Min T. Nanocurcumin: a promising candidate for therapeutic applications. Front Pharmacol 2020;11:1-24.
66. Bernkop Schnürch A, Dünnhaupt S. Chitosan-based drug delivery systems. Eur J Pharm Biopharm 2012;81:463-9.
67. Maftoonazad N, Badii F, Shahamirian M. Recent innovations in the area of edible films and coatings. Recent Pat Food Nutr Agric 2013;5:201-13.
68. Maluin FN, Hussein MZ. Chitosan-based agronanochemicals as a sustainable alternative in crop protection. Molecules 2020;25:1-22.
69. Phuong Ngo TM, Nguyen TH, Quyen Dang TM, Tran TX, Rachtanapun P. Characteristics and antimicrobial properties of active edible films based on pectin and nanochitosan. Int J Mol Sci 2020;21:1-16.
70. Owolabi JO, Ghazal OK, Williams FE, Ayodele EO. Effect of Moringa oleifera (drumstick) leaf extracts on lead-induced testicular toxicity in adult wistar rat (Rattus novergicus). Int J Biotechnol Biomed Res 2012;2:4003-9.
71. Klebanoff S. Myeloperoxidase: friend and foe. J leukoc Biol 2005;77:1-28.
72. Malle E, Woenckhaus C, Waeg G, Esterbauer H, Grone E, Grone H. Immunological evidence for hypochlorite-modified proteins in human kidney. Am J Pathol 1997;150:603-15.
73. Grone HJ, Grone E, Malle E. Immunohistochemical detection of hypochlorite-modified proteins in glomeruli of human membranous glomerulonephritis. Lab Invest 2002;82:5-14.
74. Odobasic D, Kitching AR, Semple TJ, Holdsworth SR. Endogenous myeloperoxidase promotes neutrophil-mediated renal injury, but attenuates t cell immunity inducing crescentic glomerulonephritis. J Am Soc Nephrol 2007;18:760-70.
75. Ansar S, Farhat S, Albati AAM, Abudawood M, Hamed S. Effect of curcumin and curcumin nanoparticles against lead-induced nephrotoxicity. Biomed Res 2019;30:57-60.
76. Abdel Wahhab MA, Aljawish A, El-Nekeety AA, Abdel-Aziem SH, Hassan NS. Chitosan nanoparticles plus quercetin suppress the oxidative stress, modulate DNA fragmentation and gene expression in the kidney of rats fed ochratoxin A-contaminated diet. Food Chem Toxicol 2017;99:209-21.
77. Karabay NU, Oguz MG. Cytogenetic genotoxic effects of the insecticides, imidacloprid methamidophos. Genet Mol Res 2005;4:653-62.
78. Itoh S, Shimada H. Micronucleus induction by chromium and selenium, and suppression by metallothionein inducer. Mutat Res 1996;367:233-6.
79. Wang XF, Xing ML, Shen Y, Zhu X, Xu LH. Oral administration of Cr (VI) induced oxidative stress, DNA damage and apoptotic cell death in mice. Toxicology 2006;228:16-23.
80. Wise SS, Holmes AL, Wise SR. Hexavalent chromium-induced DNA damage and repair mechanisms. Rev Environ Health 2008;23:39-57.
81. Sankar P, Telang AG, Ramya K, Vijayakaran K, Kesavan M, Sarkar SN. Protective action of curcumin and nano-curcumin against arsenic-induced genotoxicity in rats in vivo. Mole Biol Rep 2014;41:7413-22.
82. Dana Devi K, Rozati R, Saleha Banu B, Jamil K, Grover P. In vivo genotoxic effect of potassium dichromate in mice leukocytes using the comet assay. Food Chem Toxicol 2001;39:859-65.
83. Patlolla AK, Barnes C, Yedjou C, Velma VR, Tchounwou PB. Oxidative stress, DNA damage, and antioxidant enzyme activity induced by hexavalent chromium in sprague-dawley rats. Environ Toxicol 2009a;24:66-73.
84. Patlolla AK, Barnes C, Hackett D, Tchounwou PB. Potassium dichromate induced cytotoxicity, genotoxicity and oxidative stress in human liver carcinoma (HepG2) cells. Int J Environ Res Public Health 2009b;6:643-53.
85. Cengiz M, Alansal NO, Tuncdemir M, Tanriverdi G, Bayoglu B. Evaluation of effects of melatonin and caffeic acid phenethyl ester on acute potassium dichromate toxicity and genotoxicity in rats. Indian J Pharmacol 2016;48:407-11.
86. Sankar P, Telang AG, Kalaivanan R, Vijayakaran K, Kesavan M, Sarkar SN. Effects of nanoparticle-encapsulated curcumin on arsenic-induced liver toxicity in rats. Environ Toxicol 2013b;30:628-37.
87. Sankar P, Telang AG, Kalaivanan R, Vijayakaran K, Kesavan M, Suresh S, et al. Oral nanoparticulate curcumin combating arsenic-induced oxidative damage in kidney and brain of rats. Toxicol Ind Health 2016;32:410-21.
88. Rajeswari A. Curcumin protects mouse brain from oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine. Eur Rev Med Pharmacol Sci 2006;10:157-61.
89. Niture SK, Velu CS, Smith QR, Bhat GJ, Srivenugopal KS. Increased expression of the MGMT repair protein mediated by cysteine prodrugs chemopreventative natural products in human lymphocytes tumor cell lines. Carcinogenesis 2007;28:378-89.
90. Abdel Wahhab MA, Aljawish A, El-Nekeety AA, Abdel Aiezm SH, Abdel Kader HAM, Rihn BH, et al. Chitosan nanoparticles and quercetin modulate gene expression and prevent the genotoxicity of aflatoxin B1in rat liver. Toxicol Rep 2015;2:737-47.
91. Oliveira H, Spano M, Guevara MA, Santos TM, Santos C, Pereira ML. Evaluation of in vivo reproductive toxicity of potassium chromate in male mice. Exp Toxicol Pathol 2010;62:391-404.
92. Bashandy SA, Ahmed Farid OA, Omara EA, El-Toumy SA, Salib JY. Protective effect of Citrus reticulata peel extract against potassium dichromate-induced reproductive toxicity in rats. Asian Pac J Reprod 2019;8:267-75.
93. Sanocka D, Kurpisz M. Reactive oxygen species and sperm cells. Reprod Biol Endocrinol 2004;2:1-7.
94. Acharya UR, Mishra M, Patro J, Panda MK. Effect of vitamins C and E on spermatogenesis in mice exposed to cadmium. Reprod Toxicol 2008;25:84-8.
95. Ahmed Farid OAH, Nasr M, Ahmed RF, Bakeer RM. Beneficial effects of curcumin nano-emulsion on spermatogenesis andreproductive performance in male rats under protein-deficient diet model: enhancement of sperm motility, conservancy of testicular tissue integrity, cell energy and seminal plasma amino acids content. J Biomed Sci 2017;24:1-14.
96. Sudjarwo SA, Anwar C, Wardani G, Eraiko K, Koerniasari. Antioxidant and anti-caspase 3 effect of chitosan-Pinus merkusii extract nanoparticle against lead acetate-induced testicular toxicity in rat. Asian Pac J Reprod 2019;8:13-9.
97. Melnikov VY, Ecder T, Fantuzzi G, Siegmund B, Lucia MS, Dinarello CA, et al. Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. J Clin Invest 2001;107:1145-52.
98. Wu H, Craft ML, Wang P, Wyburn KR, Chen G, Ma J, et al. IL-18 contributes to renal damage after ischemia-reperfusion. J Am Soc Nephrol 2008;19:2331-41.
99. Oh Y. The insulin-like growth factor system in chronic kidney disease: Pathophysiology and therapeutic opportunities. Kidney Res Clin Pract 2012;31:26-37.
100. Mosa IF, Youssef M, Kamel M, Mosa OF, Helmy Y. Synergistic antioxidant capacity of CsNPs and CurNPs against cytotoxicity, genotoxicity and pro-inflammatory mediators induced by hydroxyapatite nanoparticles in male rats. Toxicol Res 2019;8:939-52.
101. Huang Y, Nakada S, Ishiko T, Utsugisawa T, Datta R, Kharbanda S, et al. Role for caspase-mediated cleavage of Rad51 in induction of apoptosis by DNA damage. Mol Cell Biol 1999;4:2986-97.
102. Mcllwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol 2013;5:1-28.
103. Leon J, Acuna Castroviejo D, Escames G, Tan DX. Melatonin mitigates mitochondrial malfunction. J Pineal Res 2005;38:1-9.
104. Taba MY, Mohammadi S, Jalali M, Farimah Beheshti F, Attari SS. Effects of different doses of curcumin on testicular histopathology, apoptosis, and reproductive organs weight index in mice D-galactose-induced aging model. Comp Clin Pathol 2019;28:997-1002.
105. Zalok FM, Madbouly SM, Abdouh ES, Elnagar DM. The potent role of smart chitosan nanoparticles on the attenuation of testicular damage cimetidin–induced in swiss albino mice. EJBPS 2019;6:115-20.
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