Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Research Article

Nano Diosgenin Abates DMBA Induced Renal and Hepatic Toxicities: Biochemical and Histopathological Evaluation on the Breast Cancer Model

Author(s): Manobharathi Vengaimaran, Kalaiyarasi Dhamodharan and Mirunalini Sankaran*

Volume 19, Issue 4, 2023

Published on: 07 November, 2022

Article ID: e180822207629 Pages: 21

DOI: 10.2174/1573407218666220818105057

Price: $65

Abstract

Background: Nature-based pharmaceuticals are now becoming an integral aspect of toxic-free healthcare therapies. Diosgenin (DN), a unique phyto steroidal sapogenin, seems to be explicitly employed as a core ingredient in countless traditional and patented Chinese medicines owing to its epic multilayered therapeutic treasure.

Objective: The prime intent of the current study was to probe the hepato- and nephro- ameliorating the impact of Diosgenin encapsulated chitosan nanoparticles (DN@CS-NPS) on 7,12- dimethylbenz(a)anthracene (DMBA) mediated rat mammary oncogenesis.

Methods: A single dosage of DMBA (25 mg/kg body weight) was injected to induce breast cancer. Oral administration of DN (10 mg/kg body weight) and DN@CS-NPS (5 mg/kg body weight) was used to medicate DMBA administered tumor-bearing rats just after the emergence of a tumor. Following the experimental duration, biochemical and histopathological (H&E) analyses have been carried out.

Results: Here, we noticed that there is an escalated level of liver and kidney biomarkers, phase-I detoxification enzymes, lipid peroxidative marker, total cholesterol (TC), phospholipids (PL), triglycerides (TG), and free fatty acids (FFA), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), total lipase (TL) as well as diminished levels of phase – II detoxification enzymes, enzymatic and non-enzymatic antioxidants, high-density lipoprotein (HDL), lipoprotein lipase (LPL) and lecithin acyltransferase (LCAT) in the plasma, liver and kidney tissues of DMBA-induced rats with renal and hepatic histopathological alterations. Conversely, oral treatment of DN@CS-NPS substantially reduced their tiers to near-normal levels.

Conclusion: Thus, our observations suggested that DN@CS-NP is an impactful hepato- and nephro- therapeutic agent that might have a significant influence on breast cancer over free DN.

Keywords: Mammary cancer, diosgenin, nanoencapsulation, liver marker enzymes, renal biomarkers, total cholesterol.

Graphical Abstract
[1]
Power, E.; Chin, M.L.; Haq, M.M. Breast cancer incidence and risk reduction in the Hispanic population. Cureus, 2018, 10(2), 1-12.
[http://dx.doi.org/10.7759/cureus.2235] [PMID: 29713580]
[2]
Ferlay, J.; Wild, C.P.; Bray, F. The burden of cancer worldwide: Current and future perspectives; Holland‐Frei Cancer Medicine 2016, 1-15.
[3]
Kumar, P.; Barua, C.C.; Sulakhiya, K.; Sharma, R.K. Curcumin ameliorates cisplatin-induced nephrotoxicity and potentiates its anticancer activity in SD rats: Potential role of curcumin in breast cancer chemotherapy. Front. Pharmacol., 2017, 8, 132.
[http://dx.doi.org/10.3389/fphar.2017.00132] [PMID: 28420987]
[4]
Koroglu-Aydın, P.; Bayrak, B.B.; Bugan, I.; Karabulut-Bulan, O.; Yanardag, R. Histological and biochemical investigation of the renoprotective effects of metformin in diabetic and prostate cancer model. Toxicol. Mech. Methods, 2021, 31(7), 489-500.
[http://dx.doi.org/10.1080/15376516.2021.1919810] [PMID: 34039237]
[5]
Sharma, D.; Smits, B.M.; Eichelberg, M.R.; Meilahn, A.L.; Muelbl, M.J.; Haag, J.D.; Gould, M.N. Quantification of epithelial cell differentiation in mammary glands and carcinomas from DMBA- and MNU-exposed rats. PLoS One, 2011, 6(10), e26145.
[http://dx.doi.org/10.1371/journal.pone.0026145] [PMID: 22022542]
[6]
Korsh, J.; Shen, A.; Aliano, K.; Davenport, T. Polycyclic aromatic hydrocarbons and breast cancer: A review of the literature. Breast Care (Basel), 2015, 10(5), 316-318.
[http://dx.doi.org/10.1159/000436956] [PMID: 26688678]
[7]
Saleha, Y.M. Gene expression and histopathology alterations during rat mammary carcinogenesis induced by 7, 12-dimethylbenz [a] anthracene and the protective role of Neem (Azadirachtaindica) leaf extract. J. Am. Sci., 2010, 6(9), 843-859.
[8]
Saravanan, D.; Baskaran, K.; Sakthisekaran, D. Protective effect of thymoquinone on the liver tissues of 7, 12-dimethylbenz (a) anthracene induced experimental breast cancer rats. Asian J. Pharm. Clin. Res., 2016, 9(3), 197-201.
[9]
Gholamine, B.; Houshmand, G.; Hosseinzadeh, A.; Kalantar, M.; Mehrzadi, S.; Goudarzi, M. Gallic acid ameliorates sodium arsenite-induced renal and hepatic toxicity in rats. Drug Chem. Toxicol., 2021, 44(4), 341-352.
[http://dx.doi.org/10.1080/01480545.2019.1591434] [PMID: 30907158]
[10]
Sheweita, S.A.; Almasmari, A.A.; El-Banna, S.G. Tramadol-induced hepato- and nephrotoxicity in rats: Role of curcumin and gallic acid as antioxidants. PLoS One, 2018, 13(8), e0202110.
[http://dx.doi.org/10.1371/journal.pone.0202110] [PMID: 30110401]
[11]
Arulkumaran, S.; Ramprasath, V.R.; Shanthi, P.; Sachdanandam, P. Alteration of DMBA-induced oxidative stress by additive action of a modified indigenous preparation--Kalpaamruthaa. Chem. Biol. Interact., 2007, 167(2), 99-106.
[http://dx.doi.org/10.1016/j.cbi.2007.01.013] [PMID: 17349985]
[12]
Saravanan, D.; Baskaran, K.; Sakthisekaran, D. Therapeutic effect of thymoquinone on 7, 12 dimethyl benz (A) anthracene (DMBA) induced experimental breast cancer. J. Pharm. Res., 2014, 8, 1836-1841.
[13]
Lakshmi, A.; Subramanian, S.P. Tangeretin ameliorates oxidative stress in the renal tissues of rats with experimental breast cancer induced by 7,12-dimethylbenz[a]anthracene. Toxicol. Lett., 2014, 229(2), 333-348.
[http://dx.doi.org/10.1016/j.toxlet.2014.06.845] [PMID: 24995432]
[14]
Nandhakumar, E.; Purushothaman, A.; Sachdanandam, P. Protective effect of Shemamruthaa on lipids anomalies in 7, 12-dimethylbenz [a] anthracene (DMBA)-induced mammary carcinoma-bearing rats. Med. Chem. Res., 2014, 23(7), 3491-3502.
[http://dx.doi.org/10.1007/s00044-014-0921-4]
[15]
Manivannan, J.; Arunagiri, P.; Sivasubramanian, J.; Balamurugan, E. Diosgenin prevents hepatic oxidative stress, lipid peroxidation and molecular alterations in chronic renal failure rats. Int. J. Nutr. Pharmacol. Neurol. Dis., 2013, 3(3), 289.
[http://dx.doi.org/10.4103/2231-0738.114870]
[16]
Sobolewska, D.; Galanty, A.; Grabowska, K. Makowska-Wąs, J.; Wróbel-Biedrawa, D.; Podolak, I. Saponins as cytotoxic agents: An update (2010-2018). Part I-steroidal saponins. Phytochem. Rev., 2020, 19(1), 139-189.
[http://dx.doi.org/10.1007/s11101-020-09661-0]
[17]
Manobharathi, V.; Mirunalini, S. Pharmacological characteristics of a Phyto steroidal food saponin. Diosgenin. Afri. J. Biol. Sci., 2020, 2(2), 77-87.
[http://dx.doi.org/10.33472/AFJBS.2.2.2020.77-87]
[18]
Mirunalini, S.; Shahira, R. Novel effect of diosgenin–a plant derived steroid. A review. Pharmacologyonline, 2011, 1, 726-736.
[19]
Kalaiyarasi, D.; Manobharathi, V.; Mirunalini, S. Development of nano drugs: A promising avenue for cancer treatment. Res. J. Biotechnol., 2021, 16(4), 234-244.
[20]
Arulmozhi, V.; Pandian, K.; Mirunalini, S. Ellagic acid encapsulated chitosan nanoparticles for drug delivery system in human oral cancer cell line (KB). Colloids Surf. B Biointerfaces, 2013, 110, 313-320.
[http://dx.doi.org/10.1016/j.colsurfb.2013.03.039] [PMID: 23732810]
[21]
Isabella, S.; Mirunalini, S.; Pandiyan, K. 3, 3′-Diindolylmethane encapsulated chitosan nanoparticles accelerates inflammatory markers, ER/PR, glycoprotein and mast cells population during chemical carcinogen induced mammary cancer in rats. Indian J. Clin. Biochem., 2018, 33(4), 397-405.
[http://dx.doi.org/10.1007/s12291-017-0701-2] [PMID: 30319185]
[22]
Jagadeesan, J.; Nandakumar, N.; Rengarajan, T.; Balasubramanian, M.P. Diosgenin, a steroidal saponin, exhibits anticancer activity by attenuating lipid peroxidation via enhancing antioxidant defense system during NMU-induced breast carcinoma. J. Environ. Pathol. Toxicol. Oncol., 2012, 31(2), 121-129.
[http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.v31.i2.40] [PMID: 23216637]
[23]
Kumar, B.N.P.; Puvvada, N.; Rajput, S.; Sarkar, S.; Das, S.K.; Emdad, L.; Sarkar, D.; Venkatesan, P.; Pal, I.; Dey, G.; Konar, S.; Brunt, K.R.; Rao, R.R.; Mazumdar, A.; Kundu, S.C.; Pathak, A.; Fisher, P.B.; Mandal, M. Sequential release of drugs from hollow manganese ferrite nanocarriers for breast cancer therapy. J. Mater. Chem. B Mater. Biol. Med., 2015, 3(1), 90-101.
[http://dx.doi.org/10.1039/C4TB01098A] [PMID: 32261929]
[24]
Bergmeyer, H.U.; Scheibe, P.; Wahlefeld, A.W. Optimization of methods for aspartate aminotransferase and alanine aminotransferase. Clin. Chem., 1978, 24(1), 58-73.
[http://dx.doi.org/10.1093/clinchem/24.1.58] [PMID: 22409]
[25]
Huang, X.J.; Choi, Y.K. Im, H.S.; Yarimaga, O.; Yoon, E.; Kim, HS. Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) detection techniques. Sensors, 2006, 6(7), 756-782.
[http://dx.doi.org/10.3390/s6070756] [PMID: 3894536]
[26]
Balasubramanian, M.P. Comparative studies on phosphomonoesterase in helminths. Helminthologia, 1983, 20, 111-120.
[27]
Rosalki, S.B.; Rau, D. Serum -glutamyl transpeptidase activity in alcoholism. Clin. Chim. Acta, 1972, 39(1), 41-47.
[http://dx.doi.org/10.1016/0009-8981(72)90297-5] [PMID: 5038763]
[28]
Brinster, R.L. Lactate dehydrogenase activity in the preimplanted mouse embryo. Biochim. Biophys. Acta., 1965, 110(2), 439-441.
[http://dx.doi.org/10.1016/s0926-6593(65)80056-x] [PMID: 4286293]
[29]
Batton, C.J.; Crouch, S.R. Spectrophotometer investigation of urea. Anal. Chem., 1977, 49, 464-469.
[30]
Watts, R.W.E. Technical bulletin No. 31. Determination of uric acid in blood and in urine. Ann. Clin. Biochem., 1974, 11(4), 103-111.
[http://dx.doi.org/10.1177/000456327401100139] [PMID: 4608659]
[31]
Bowers, L.D.; Wong, E.T. Kinetic serum creatinine assays. II. A critical evaluation and review. Clin. Chem., 1980, 26(5), 555-561.
[http://dx.doi.org/10.1093/clinchem/26.5.555] [PMID: 7020989]
[32]
Omura, T.; Sato, R. The carbon monoxide-binding pigment of liver microsomes: I. Evidence for its hemoprotein nature. J. Biol. Chem., 1964, 239(7), 2370-2378.
[http://dx.doi.org/10.1016/S0021-9258(20)82244-3] [PMID: 14209971]
[33]
Phillips, A.H.; Langdon, R.G. Hepatic triphosphopyridine nucleotide-cytochrome c reductase: Isolation, characterization, and kinetic studies. J. Biol. Chem., 1962, 237(8), 2652-2660.
[http://dx.doi.org/10.1016/S0021-9258(19)73803-4] [PMID: 14486217]
[34]
Habig, W.H.; Pabst, M.J.; Jakoby, W.B. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J. Biol. Chem., 1974, 249(22), 7130-7139.
[http://dx.doi.org/10.1016/S0021-9258(19)42083-8] [PMID: 4436300]
[35]
Carlberg, I.; Mannervik, B. Glutathione reductase. Methods Enzymol., 1985, 113, 484-490.
[http://dx.doi.org/10.1016/S0076-6879(85)13062-4] [PMID: 3003504]
[36]
Ernster, L. DT diaphorase. Methods Enzymol., 1967, 10, 309-317.
[http://dx.doi.org/10.1016/0076-6879(67)10059-1]
[37]
Yagi, K. Lipid peroxides and human diseases. Chem. Phys. Lipids, 1987, 45, 2-4, 337-351.
[http://dx.doi.org/10.1016/0009-3084(87)90071-5]
[38]
Ohkawa, H.; Ohishi, N.; Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem., 1979, 95(2), 351-358.
[http://dx.doi.org/10.1016/0003-2697(79)90738-3] [PMID: 36810]
[39]
Kakkar, P.; Das, B.; Viswanathan, P.N. A modified spectrophotometric assay of superoxide dismutase. Indian J. Biochem. Biophys., 1984, 21(2), 130-132.
[PMID: 6490072]
[40]
Sinha, A.K. Colorimetric assay of catalase. Anal. Biochem., 1972, 47(2), 389-394.
[http://dx.doi.org/10.1016/0003-2697(72)90132-7] [PMID: 4556490]
[41]
Rotruck, J.T.; Pope, A.L.; Ganther, H.E.; Swanson, A.B.; Hafeman, D.G.; Hoekstra, W.G. Selenium: Biochemical role as a component of glutathione peroxidase. Science, 1973, 179(4073), 588-590.
[http://dx.doi.org/10.1126/science.179.4073.588] [PMID: 4686466]
[42]
Ellman, G.L. Tissue sulfhydryl groups. Arch. Biochem. Biophys., 1959, 82(1), 70-77.
[http://dx.doi.org/10.1016/0003-9861(59)90090-6] [PMID: 13650640]
[43]
Omaye, S.T.; Turnbull, J.D.; Sauberlich, H.E. Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol., 1979, 62, 3-11.
[http://dx.doi.org/10.1016/0076-6879(79)62181-X] [PMID: 440112]
[44]
Desai, I.D. Vitamin E analysis methods for animal tissues. Methods Enzymol., 1984, 105, 138-147.
[http://dx.doi.org/10.1016/S0076-6879(84)05019-9] [PMID: 6727662]
[45]
Folch, J.; Lees, M.; Sloane Stanley, G.H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem., 1957, 226(1), 497-509.
[http://dx.doi.org/10.1016/S0021-9258(18)64849-5] [PMID: 13428781]
[46]
Zlatkis, A.; Zak, B.; Boyle, A.J. A new method for the direct determination of serum cholesterol. J. Lab. Clin. Med., 1953, 41(3), 486-492.
[PMID: 13035283]
[47]
Foster, L.B.; Dunn, R.T. Stable reagents for determination of serum triglycerides by a colorimetric Hantzsch condensation method. Clin. Chem., 1973, 19(3), 338-340.
[http://dx.doi.org/10.1093/clinchem/19.3.338] [PMID: 4347544]
[48]
Falholt, K.; Lund, B.; Falholt, W. An easy colorimetric micromethod for routine determination of free fatty acids in plasma. Clin. Chim. Acta, 1973, 46(2), 105-111.
[http://dx.doi.org/10.1016/0009-8981(73)90016-8] [PMID: 4745354]
[49]
Zilversmit, D.B.; Davis, A.K. Microdetermination of plasma phospholipids by trichloroacetic acid precipitation. J. Lab. Clin. Med., 1950, 35(1), 155-160.
[PMID: 15400638]
[50]
Burstein, M.; Scholnick, H.R.; Morfin, R. Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J. Lipid Res., 1970, 11(6), 583-595.
[http://dx.doi.org/10.1016/S0022-2275(20)42943-8] [PMID: 4100998]
[51]
Kapoor, R.; Chakraborty, M.; Singh, N. A leap above Friedewald formula for calculation of low-density lipoprotein-cholesterol. J. Lab. Phys., 2015, 7(1), 11-16.
[http://dx.doi.org/10.4103/0974-2727.154780] [PMID: 25949053]
[52]
Bier, M. Enzymes of lipid metabolism. Lipases and esterases. Methods Enzymol., 1955, 1, 631-638.
[53]
Baginsky, M.L. Measurement of lipoprotein lipase and hepatic triglyceride lipase in human postheparin plasma. Methods Enzymol., 1981, 72, 325-338.
[http://dx.doi.org/10.1016/S0076-6879(81)72023-8] [PMID: 7031422]
[54]
Legraud, A.; Guillansseav, R.J.; Land, J. Method. Colorimetric simple determination del’actirit, de la lecithin cholesterol acyl transferase (LCAT) plasma fique. Interest on diabetologic. Biological prospective; Masson: Paris, 1979, pp. 368-371.
[55]
Hitz, J.; Steinmetz, J.; Siest, G. Plasma lecithin:cholesterol acyltransferase - reference values and effects of xenobiotics. Clin. Chim. Acta, 1983, 133(1), 85-96.
[http://dx.doi.org/10.1016/0009-8981(83)90023-2] [PMID: 6627678]
[56]
Shamsuddin, A.K.M.; Trump, B.F. Colon epithelium. II. In vivo studies of colon carcinogenesis. Light microscopic, histochemical, and ultrastructural studies of histogenesis of azoxymethane-induced colon carcinomas in Fischer 344 rats. J. Natl. Cancer Inst., 1981, 66(2), 389-401.
[PMID: 6935486]
[57]
Maruthanila, V.L.; Elancheran, R.; Kunnumakkara, A.B.; Kabilan, S.; Kotoky, J. Recent development of targeted approaches for the treatment of breast cancer. Breast Cancer, 2017, 24(2), 191-219.
[http://dx.doi.org/10.1007/s12282-016-0732-1] [PMID: 27796923]
[58]
Li, J.; Cai, C.; Li, J.; Li, J.; Li, J.; Sun, T.; Wang, L.; Wu, H.; Yu, G. Chitosan-based nanomaterials for drug delivery. Molecules, 2018, 23(10), 2661.
[http://dx.doi.org/10.3390/molecules23102661] [PMID: 30332830]
[59]
Giannini, E.G.; Testa, R.; Savarino, V. Liver enzyme alteration: A guide for clinicians. CMAJ, 2005, 172(3), 367-379.
[http://dx.doi.org/10.1503/cmaj.1040752] [PMID: 15684121]
[60]
Jiang, J.T.; Xu, N.; Zhang, X.Y.; Wu, C.P. Lipids changes in liver cancer. J. Zhejiang Univ. Sci. B, 2007, 8(6), 398-409.
[http://dx.doi.org/10.1631/jzus.2007.B0398] [PMID: 17565510]
[61]
Chen, B.; Dai, D.; Tang, H.; Chen, X.; Ai, X.; Huang, X.; Wei, W.; Xie, X. Pre-treatment serum alkaline phosphatase and lactate dehydrogenase as prognostic factors in triple negative breast cancer. J. Cancer, 2016, 7(15), 2309-2316.
[http://dx.doi.org/10.7150/jca.16622] [PMID: 27994669]
[62]
Zhang, L.X.; Lv, Y.; Xu, A.M.; Wang, H.Z. The prognostic significance of serum gamma-glutamyltransferase levels and AST/ALT in primary hepatic carcinoma. BMC Cancer, 2019, 19(1), 841.
[http://dx.doi.org/10.1186/s12885-019-6011-8] [PMID: 31455253]
[63]
Akhouri, V.; Kumari, M.; Kumar, A. Therapeutic effect of Aegle marmelos fruit extract against DMBA induced breast cancer in rats. Sci. Rep., 2020, 10(1), 18016.
[http://dx.doi.org/10.1038/s41598-020-72935-2] [PMID: 33093498]
[64]
Williams, J.A.; Phillips, D.H. Mammary expression of xenobiotic metabolizing enzymes and their potential role in breast cancer. Cancer Res., 2000, 60(17), 4667-4677.
[PMID: 10987265]
[65]
Singh, M.S.; Michael, M. Role of xenobiotic metabolic enzymes in cancer epidemiology. Methods Mol. Biol., 2009, 472, 243-264.
[http://dx.doi.org/10.1007/978-1-60327-492-0_10] [PMID: 19107436]
[66]
Justenhoven, C. Polymorphisms of phase I and phase II enzymes and breast cancer risk. Front. Genet., 2012, 3, 258.
[http://dx.doi.org/10.3389/fgene.2012.00258] [PMID: 23226154]
[67]
Bishayee, A.; Oinam, S.; Basu, M.; Chatterjee, M. Vanadium chemoprevention of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinogenesis: Probable involvement of representative hepatic phase I and II xenobiotic metabolizing enzymes. Breast Cancer Res. Treat., 2000, 63(2), 133-145.
[http://dx.doi.org/10.1023/A:1006476003685] [PMID: 11097089]
[68]
Wang, W.; Bai, L.; Li, W.; Cui, J. The lipid metabolic landscape of cancers and new therapeutic perspectives. Front. Oncol., 2020, 10, 605154.
[http://dx.doi.org/10.3389/fonc.2020.605154] [PMID: 33364199]
[69]
Saba, A.B.; Ajibade, T. Role of lipoproteins in carcinogenesis and in chemoprevention; IntechOpen, 2012.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy