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Pre-treatment with Beta Carotene Gives Protection Against Nephrotoxicity Induced by Bromobenzene via Modulation of Antioxidant System, Pro-inflammatory Cytokines and Pro-apoptotic Factors

  • Priya Josson Akkara
  • Evan Prince SabinaEmail author
Article
  • 6 Downloads

Abstract

Bromobenzene is an environmental toxin which causes hepatotoxicity, and the secondary metabolites on biotransformation cause nephrotoxicity. The objective of this study was to assess the alleviation of the nephrotoxic effect of bromobenzene by beta carotene in female Wistar albino rats. Beta carotene (10 mg/kg b.w.p.o.) was delivered orally to the rats for 9 days before bromobenzene (10 mM/kg b.w.p.o.) was intragastrically intubated. Kidney markers, antioxidant status and lipid peroxidation were evaluated. In addition, the levels of TNF-α, IL-6 and IL-1β were measured in serum and in kidney tissue homogenate using ELISA. Caspase, COX-2 and NF-κB were measured with the help of Western blotting. Histopathological analysis of the kidney was done for the control and experimental rats. Bromobenzene induction caused elevation in levels of creatinine, urea, uric acid, cytokines and lipid per oxidation along with deterioration in histological observations and antioxidant status. Pre-treatment with beta carotene significantly (*p < 0.05) normalised the levels of kidney markers and pro-inflammatory cytokines. It also reduced oxidative stress and lipid peroxidation, as shown by improved antioxidant status. The anti-apoptotic activity was evidenced by inhibition of protein expression of caspase, COX-2 and NF-κB. This significant reversal (*p < 0.05) of the above variations in comparison with the control group as noticed in the bromobenzene-administered rats demonstrates that beta carotene possesses promising nephroprotective effect through its antioxidant, anti-inflammatory and anti-apoptotic activity and therefore suggests its use as a potential therapeutic agent for protection from bromobenzene and hence environmental pollutant toxicity.

Keywords

Nephrotoxicity Bromobenzene Beta carotene Inflammatory Apoptosis Antioxidant 

Notes

Acknowledgements

The authors are thankful to VIT University for extending the required facilities to carry out this research project.

Compliance with Ethical Standards

Approval was given by the ethical committee of the institution, VIT University, Vellore, India (VIT/IAEC/13/Feb13/20), for the experimental procedure.

Conflict of Interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Van Vleet, T. R., & Schnellmann, R. G. (2003). Toxic nephropathy: environmental chemicals. Seminars in Nephrology, 23(5), 500–508.Google Scholar
  2. 2.
    Pfister, F., Büttner-Herold, M., & Amann, K. (2018). (Immun-)Pathologie von Medikamentennebenwirkungen in der Niere. Der Pathologe., 39(6), 576–582.  https://doi.org/10.1007/s00292-018-0475-1.Google Scholar
  3. 3.
    Elseweidy, M. M., Askar, M. E., Elswefy, S. E., & Shawky, M. (2018). Nephrotoxicity induced by cisplatin intake in experimental rats and therapeutic approach of using mesenchymal stem cells and spironolactone. Applied Biochemistry and Biotechnology, 184(4), 1390–1403.  https://doi.org/10.1007/s12010-017-2631-0.Google Scholar
  4. 4.
    Gopi, S., & Setty, O. H. (2010). Beneficial effect of the administration of Hemidesmus indicus against bromobenzene induced oxidative stress in rat liver mitochondria. Journal of Ethnopharmacology, 127(1), 200–203.  https://doi.org/10.1016/j.jep.2009.09.043.Google Scholar
  5. 5.
    Hamed, M. A., El-Rigal, N. S., & Ali, S. A. (2013). Effects of black seed oil on resolution of hepato-renal toxicity induced by bromobenzene in rats. European Review for Medical and Pharmacological Sciences, 17(5), 569–581.Google Scholar
  6. 6.
    Madhu, C., & Klaassen, C. D. (1992). Bromobenzene-glutathione excretion into bile reflects toxic activation of bromobenzene in rats. Toxicology Letters, 60(2), 227–236.Google Scholar
  7. 7.
    Jollow, D. J., Mitchell, J. R., Zampaglione, N., & Gillette, J. R. (1974). Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology, 11(3), 151–169.  https://doi.org/10.1159/000136485.Google Scholar
  8. 8.
    Abraham, P., Ramamoorthy, H., & Isaac, B. (2013). Depletion of the cellular antioxidant system contributes to tenofovir disoproxil fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in the kidney. Journal of Biomedical Science, 20(1), 61.  https://doi.org/10.1186/1423-0127-20-61.Google Scholar
  9. 9.
    Kalantari, H., Jalali, M., Jalali, A., Salimi, A., Alhalvachi, F., Varga, B., Juhasz, B., Jakab, A., Kemeny-Beke, A., Gesztelyi, R., Tosaki, A., & Zsuga, J. (2011). Protective effect of Cassia fistula fruit extract on bromobenzene-induced nephrotoxicity in mice. Human & Experimental Toxicology, 30(10), 1710–1715.  https://doi.org/10.1177/0960327110396532.Google Scholar
  10. 10.
    Putakala, M., Gujjala, S., Nukala, S., & Desireddy, S. (2017). Beneficial effects of Phyllanthus amarus against high fructose diet induced insulin resistance and hepatic oxidative stress in male Wistar rats. Applied Biochemistry and Biotechnology, 183(3), 744–764.  https://doi.org/10.1007/s12010-017-2461-0.Google Scholar
  11. 11.
    Sarker, U., & Oba, S. (2018). Drought stress effects on growth, ROS markers, compatible solutes, phenolics, flavonoids, and antioxidant activity in Amaranthus tricolor. Applied Biochemistry and Biotechnology, 186(4), 999–1016.  https://doi.org/10.1007/s12010-018-2784-5.Google Scholar
  12. 12.
    da Rocha, P. D. S., Campos, J. F., Nunes-Souza, V., Vieira, M. d. C., Boleti, A. P. d. A., Rabelo, L. A., & de Picoli Souza, K. (2018). Antioxidant and protective effects of Schinus terebinthifolius Raddi against doxorubicin-induced toxicity. Applied Biochemistry and Biotechnology, 184(3), 869–884.  https://doi.org/10.1007/s12010-017-2589-y.Google Scholar
  13. 13.
    Hirahatake, K. M., Jacobs, D. R., Gross, M. D., Bibbins-Domingo, K. B., Shlipak, M. G., Mattix-Kramer, H., & Odegaard, A. O. (2018). The Association of serum carotenoids, tocopherols, and ascorbic acid with rapid kidney function decline: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Journal of Renal Nutrition: The Official Journal of the Council on Renal Nutrition of the National Kidney Foundation., 29(1), 65–73.  https://doi.org/10.1053/j.jrn.2018.05.008.Google Scholar
  14. 14.
    Darwish, W. S., Ikenaka, Y., Nakayama, S., Mizukawa, H., Thompson, L. A., & Ishizuka, M. (2018). β-Carotene and retinol reduce benzo[a]pyrene-induced mutagenicity and oxidative stress via transcriptional modulation of xenobiotic metabolizing enzymes in human HepG2 cell line. Environmental Science and Pollution Research International, 25(7), 6320–6328.  https://doi.org/10.1007/s11356-017-0977-z.Google Scholar
  15. 15.
    Acar, A., Yalçin, E., & Çavuşoğlu, K. (2018). Protective effects of β-carotene against ammonium sulfate toxicity: biochemical and histopathological approach in mice model. Journal of Medicinal Food, 21(11):1145–1149.  https://doi.org/10.1089/jmf.2017.4164
  16. 16.
    Bast, A., Haenen, G. R., van den Berg, R., & van den Berg, H. (1998). Antioxidant effects of carotenoids. International Journal for Vitamin and Nutrition Research. Internationale Zeitschrift Fur Vitamin- Und Ernahrungsforschung. Journal International De Vitaminologie Et De Nutrition, 68(6), 399–403.Google Scholar
  17. 17.
    Beta-carotene. (2006). In Drugs and Lactation Database (LactMed). Bethesda (MD): National Library of 469 Medicine (US). LactMed Record Number 985 Bookshelf ID: NBK501906PMID: CASRN: 7235–40–7Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK501906/
  18. 18.
    Zhang, Y., Zhu, X., Huang, T., Chen, L., Liu, Y., Li, Q., Song, J., Ma, S., Zhang, K., Yang, B., & Guan, F. (2016). β-Carotene synergistically enhances the anti-tumor effect of 5-fluorouracil on esophageal squamous cell carcinoma in vivo and in vitro. Toxicology Letters, 261, 49–58.  https://doi.org/10.1016/j.toxlet.2016.08.010.Google Scholar
  19. 19.
    Das, R., Das, A., Roy, A., Kumari, U., Bhattacharya, S., & Haldar, P. K. (2015). β-Carotene ameliorates arsenic-induced toxicity in albino mice. Biological Trace Element Research, 164(2), 226–233.  https://doi.org/10.1007/s12011-014-0212-4.Google Scholar
  20. 20.
    Tan, H.-L., Moran, N. E., Cichon, M. J., Riedl, K. M., Schwartz, S. J., Erdman, J. W., et al. (2014). β-Carotene-9′,10′-oxygenase status modulates the impact of dietary tomato and lycopene on hepatic nuclear receptor-, stress-, and metabolism-related gene expression in mice. The Journal of Nutrition, 144(4), 431–439.  https://doi.org/10.3945/jn.113.186676.Google Scholar
  21. 21.
    Sarada, S. K. S., Dipti, P., Anju, B., Pauline, T., Kain, A. K., Sairam, M., Sharma, S. K., Ilavazhagan, G., Kumar, D., & Selvamurthy, W. (2002). Antioxidant effect of beta-carotene on hypoxia induced oxidative stress in male albino rats. Journal of Ethnopharmacology, 79(2), 149–153.Google Scholar
  22. 22.
    Vedi, M., Rasool, M., & Sabina, E. P. (2014). Amelioration of bromobenzene hepatotoxicity by Withania somnifera pretreatment: role of mitochondrial oxidative stress. Toxicology Reports, 1, 629–638.  https://doi.org/10.1016/j.toxrep.2014.08.009.Google Scholar
  23. 23.
    Vedi, M., Rasool, M., & Sabina, E. P. (2014). Protective effect of administration of Withania somifera against bromobenzene induced nephrotoxicity and mitochondrial oxidative stress in rats. Renal Failure, 36(7), 1095–1103.  https://doi.org/10.3109/0886022X.2014.918812.Google Scholar
  24. 24.
    Marklund, S., & Marklund, G. (1974). Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European Journal of Biochemistry, 47(3), 469–474.Google Scholar
  25. 25.
    Sinha, A. K. (1972). Colorimetric assay of catalase. Analytical Biochemistry, 47(2), 389–394.Google Scholar
  26. 26.
    Habig, W. H., Pabst, M. J., & Jakoby, W. B. (1974). Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. The Journal of Biological Chemistry, 249(22), 7130–7139.Google Scholar
  27. 27.
    Rotruck, J. T., Pope, A. L., Ganther, H. E., Swanson, A. B., Hafeman, D. G., & Hoekstra, W. G. (1973). Selenium: biochemical role as a component of glutathione peroxidase. Science (New York, N.Y.), 179(4073), 588–590.  https://doi.org/10.1126/science.179.4073.588
  28. 28.
    Moron, M., Depierre, J., & Mannervik, B. (1979). Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochimica et Biophysica Acta (BBA) - General Subjects, 582(1), 67–78.  https://doi.org/10.1016/0304-4165(79)90289-7.Google Scholar
  29. 29.
    Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2), 351–358.Google Scholar
  30. 30.
    Reyes, J. L., Molina-Jijón, E., Rodríguez-Muñoz, R., Bautista-García, P., Debray-García, Y., & Namorado, M. d. C. (2013). Tight junction proteins and oxidative stress in heavy metals-induced nephrotoxicity. BioMed Research International, 2013, 1–14.  https://doi.org/10.1155/2013/730789.Google Scholar
  31. 31.
    Verma, N., Yadav, A., Bal, S., Gupta, R., & Aggarwal, N. (2019). In vitro studies on ameliorative effects of limonene on cadmium-induced genotoxicity in cultured human peripheral blood lymphocytes. Applied Biochemistry and Biotechnology, 187(4), 1384–1397.  https://doi.org/10.1007/s12010-018-2881-5.Google Scholar
  32. 32.
    Tavafi, M., & Ahmadvand, H. (2011). Effect of rosmarinic acid on inhibition of gentamicin induced nephrotoxicity in rats. Tissue & Cell, 43(6), 392–397.  https://doi.org/10.1016/j.tice.2011.09.001.Google Scholar
  33. 33.
    Jaeschke, H., McGill, M. R., & Ramachandran, A. (2012). Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity. Drug Metabolism Reviews, 44(1), 88–106.  https://doi.org/10.3109/03602532.2011.602688.Google Scholar
  34. 34.
    Dounousi, E., Papavasiliou, E., Makedou, A., Ioannou, K., Katopodis, K. P., Tselepis, A., Siamopoulos, K. C., & Tsakiris, D. (2006). Oxidative stress is progressively enhanced with advancing stages of CKD. American Journal of Kidney Diseases, 48(5), 752–760.  https://doi.org/10.1053/j.ajkd.2006.08.015.Google Scholar
  35. 35.
    Himmelfarb, J. (2004). Oxidative stress is increased in critically ill patients with acute renal failure. Journal of the American Society of Nephrology, 15(9), 2449–2456.  https://doi.org/10.1097/01.ASN.0000138232.68452.3B.Google Scholar
  36. 36.
    Singh, R., Kaur, B., Kalina, I., Popov, T. A., Georgieva, T., Garte, S., Binkova, B., Sram, R. J., Taioli, E., & Farmer, P. B. (2007). Effects of environmental air pollution on endogenous oxidative DNA damage in humans. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 620(1–2), 71–82.  https://doi.org/10.1016/j.mrfmmm.2007.02.024.Google Scholar
  37. 37.
    Therond, P. (2006). Dommages créés aux biomolécules (lipides, protéines, ADN) par le stress oxydant. Annales Pharmaceutiques Françaises, 64(6), 383–389.  https://doi.org/10.1016/S0003-4509(06)75333-0.Google Scholar
  38. 38.
    Yu, H., Ge, Y., Wang, Y., Lin, C.-T., Li, J., Liu, X., Zang, T., Xu, J., Liu, J., Luo, G., & Shen, J. (2007). A fused selenium-containing protein with both GPx and SOD activities. Biochemical and Biophysical Research Communications, 358(3), 873–878.  https://doi.org/10.1016/j.bbrc.2007.05.007.Google Scholar
  39. 39.
    Monks, T. J., & Lau, S. S. (1990). Nephrotoxicity of quinol/quinone-linked S-conjugates. Toxicology Letters, 53(1–2), 59–67.Google Scholar
  40. 40.
    Szymonik-Lesiuk, S., Czechowska, G., Stryjecka-Zimmer, M., Słomka, M., Madro, A., Celiński, K., & Wielosz, M. (2003). Catalase, superoxide dismutase, and glutathione peroxidase activities in various rat tissues after carbon tetrachloride intoxication. Journal of Hepato-Biliary-Pancreatic Surgery, 10(4), 309–315.  https://doi.org/10.1007/s00534-002-0824-5.Google Scholar
  41. 41.
    Kluwe, W. M., Maronpot, R. R., Greenwell, A., & Harrington, F. (1984). Interactions between bromobenzene dose, glutathione concentrations, and organ toxicities in single- and multiple-treatment studies. Toxicological Sciences, 4(6), 1019–1028.  https://doi.org/10.1093/toxsci/4.6.1019.Google Scholar
  42. 42.
    Locke, S. J., & Brauer, M. (1991). The response of the rat liver in situ to bromobenzene—in vivo proton magnetic resonance imaging and 31P magnetic resonance spectroscopy studies. Toxicology and Applied Pharmacology, 110(3), 416–428.  https://doi.org/10.1016/0041-008X(91)90043-E.Google Scholar
  43. 43.
    Wang, B. H., Zuzel, K. A., Rahman, K., & Billington, D. (1998). Protective effects of aged garlic extract against bromobenzene toxicity to precision cut rat liver slices. Toxicology, 126(3), 213–222.  https://doi.org/10.1016/S0300-483X(98)00018-3.Google Scholar
  44. 44.
    Abdel Moneim, A. E., Dkhil, M. A., & Al-Quraishy, S. (2011). The protective effect of flaxseed oil on lead acetate-induced renal toxicity in rats. Journal of Hazardous Materials, 194, 250–255.  https://doi.org/10.1016/j.jhazmat.2011.07.097.Google Scholar
  45. 45.
    Choudhary, A. K., & Devi, R. S. (2014). Serum biochemical responses under oxidative stress of aspartame in wistar albino rats. Asian Pacific Journal of Tropical Disease, 4, S403–S410.  https://doi.org/10.1016/S2222-1808(14)60478-3.Google Scholar
  46. 46.
    Comporti, M. (1987). Glutathione depleting agents and lipid peroxidation. Chemistry and Physics of Lipids, 45(2–4), 143–169.  https://doi.org/10.1016/0009-3084(87)90064-8.Google Scholar
  47. 47.
    Comporti, M., Maellaro, E., Del Bello, B., & Casini, A. F. (1991). Glutathione depletion: Its effects on other antioxidant systems and hepatocellular damage. Xenobiotica, 21(8), 1067–1076.  https://doi.org/10.3109/00498259109039546.Google Scholar
  48. 48.
    Bailey, S. M., & Cunningham, C. C. (2002). Contribution of mitochondria to oxidative stress associated with alcoholic liver disease. Free Radical Biology & Medicine, 32(1), 11–16.Google Scholar
  49. 49.
    S, J. P., & Evan Prince, S. (2018). Diclofenac-induced renal toxicity in female Wistar albino rats is protected by the pre-treatment of aqueous leaves extract of Madhuca longifolia through suppression of inflammation, oxidative stress and cytokine formation. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 98, 45–51.  https://doi.org/10.1016/j.biopha.2017.12.028.Google Scholar
  50. 50.
    Ratliff, B. B., Abdulmahdi, W., Pawar, R., & Wolin, M. S. (2016). Oxidant mechanisms in renal injury and disease. Antioxidants & Redox Signaling, 25(3), 119–146.  https://doi.org/10.1089/ars.2016.6665.Google Scholar
  51. 51.
    Li, J.-M., & Shah, A. M. (2004). Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 287(5), R1014–R1030.  https://doi.org/10.1152/ajpregu.00124.2004.Google Scholar
  52. 52.
    Kawata, A., Murakami, Y., Suzuki, S., & Fujisawa, S. (2018). Anti-inflammatory activity of β-carotene, lycopene and tri-n-butylborane, a scavenger of reactive oxygen species. In Vivo (Athens, Greece), 32(2), 255–264.  https://doi.org/10.21873/invivo.11232.Google Scholar
  53. 53.
    Suraiya, S., Jang, W. J., Cho, H. J., Choi, Y. B., Park, H. D., Kim, J.-M., & Kong, I.-S. (2019). Immunomodulatory effects of Monascus spp.-fermented Sacccharina japonica extracts on the cytokine gene expression of THP-1 cells. Applied Biochemistry and Biotechnology, 188(2), 498–513.  https://doi.org/10.1007/s12010-018-02930-x.Google Scholar
  54. 54.
    Benedetti, G., Fredriksson, L., Herpers, B., Meerman, J., van de Water, B., & de Graauw, M. (2013). TNF-α-mediated NF-κB survival signaling impairment by cisplatin enhances JNK activation allowing synergistic apoptosis of renal proximal tubular cells. Biochemical Pharmacology, 85(2), 274–286.  https://doi.org/10.1016/j.bcp.2012.10.012.Google Scholar
  55. 55.
    Zhou, L., Ouyang, L., Lin, S., Chen, S., Liu, Y., Zhou, W., & Wang, X. (2018). Protective role of β-carotene against oxidative stress and neuroinflammation in a rat model of spinal cord injury. International Immunopharmacology, 61, 92–99.  https://doi.org/10.1016/j.intimp.2018.05.022.Google Scholar
  56. 56.
    Rodríguez-Rodríguez, E., López-Sobaler, A. M., Navia, B., Andrés, P., Jiménez-Ortega, A. I., & Ortega, R. M. (2017). β-Carotene concentration and its association with inflammatory biomarkers in Spanish schoolchildren. Annals of Nutrition & Metabolism, 71(1–2), 80–87.  https://doi.org/10.1159/000479009.Google Scholar
  57. 57.
    Liu, X.–Y., Hwang, E., Park, B., Xiao, Y.–K., & Yi, T.–H. (2019). Photoprotective and anti–inflammatory properties of vina–ginsenoside R7 ameliorate ultraviolet B–induced photodamage in normal human dermal fibroblasts. Applied Biochemistry and Biotechnology.  https://doi.org/10.1007/s12010-019-03027-9  https://doi.org/10.1007/s12010-019-03027-9.
  58. 58.
    Stepień, A., Izdebska, M., & Grzanka, A. (2007). The types of cell death. Postepy Higieny I Medycyny Doswiadczalnej (Online), 61, 420–428.Google Scholar
  59. 59.
    Shang, Y., Myers, M., & Brown, M. (2002). Formation of the androgen receptor transcription complex. Molecular Cell, 9(3), 601–610.Google Scholar
  60. 60.
    Choudhary, G. S., Al-harbi, S., & Almasan, A. (2015). Caspase-3 activation is a critical determinant of genotoxic stress-induced apoptosis. In G. Mor & A. B. Alvero (Eds.), Apoptosis and Cancer (Vol. 1219, pp. 1–9). New York, NY: Springer New York.  https://doi.org/10.1007/978-1-4939-1661-0_1.Google Scholar
  61. 61.
    Rossi, S. P., Windschüttl, S., Matzkin, M. E., Rey-Ares, V., Terradas, C., Ponzio, R., Puigdomenech, E., Levalle, O., Calandra, R. S., Mayerhofer, A., & Frungieri, M. B. (2016). Reactive oxygen species (ROS) production triggered by prostaglandin D2 (PGD2) regulates lactate dehydrogenase (LDH) expression/activity in TM4 Sertoli cells. Molecular and Cellular Endocrinology, 434, 154–165.  https://doi.org/10.1016/j.mce.2016.06.021.Google Scholar
  62. 62.
    Cillero-Pastor, B., Caramés, B., Lires-Deán, M., Vaamonde-García, C., Blanco, F. J., & López-Armada, M. J. (2008). Mitochondrial dysfunction activates cyclooxygenase 2 expression in cultured normal human chondrocytes. Arthritis and Rheumatism, 58(8), 2409–2419.  https://doi.org/10.1002/art.23644.Google Scholar
  63. 63.
    Korashy, H. M., & El-Kadi, A. O. S. (2008). NF-κB and AP-1 are key signaling pathways in the modulation of NAD(P)H:quinone oxidoreductase 1 gene by mercury, lead, and copper. Journal of Biochemical and Molecular Toxicology, 22(4), 274–283.  https://doi.org/10.1002/jbt.20238.Google Scholar
  64. 64.
    Zhang, G., & Ghosh, S. (2001). Toll-like receptor–mediated NF-κB activation: a phylogenetically conserved paradigm in innate immunity. Journal of Clinical Investigation, 107(1), 13–19.  https://doi.org/10.1172/JCI11837.Google Scholar
  65. 65.
    Chew, B. P., & Park, J. S. (2004). Carotenoid action on the immune response. The Journal of Nutrition, 134(1), 257S–261S.  https://doi.org/10.1093/jn/134.1.257S.Google Scholar
  66. 66.
    Abu Bakar, M. H., Azmi, M. N., Shariff, K. A., & Tan, J. S. (2019). Withaferin A protects against high-fat diet-induced obesity via attenuation of oxidative stress, inflammation, and insulin resistance. Applied Biochemistry and Biotechnology, 188(1), 241–259.  https://doi.org/10.1007/s12010-018-2920-2.Google Scholar
  67. 67.
    Portt, L., Norman, G., Clapp, C., Greenwood, M., & Greenwood, M. T. (2011). Anti-apoptosis and cell survival: a review. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1813(1), 238–259.  https://doi.org/10.1016/j.bbamcr.2010.10.010.Google Scholar

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Authors and Affiliations

  1. 1.School of Bio Sciences and TechnologyVITVelloreIndia
  2. 2.Department of Life SciencesKristu Jayanti College (Autonomous)BengaluruIndia

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