Abstract
Cashew nut is a profitable cash crop and cashew nut shell liquid (CNSL) also has industrial applications. However, CNSL contains cardanol and cardol that reportedly affect the skin as well as the internal structures of the workers of cashew processing units. This study was undertaken to determine the adverse effect of CNSL in the hepatic tissue of male Wistar rats by chronic topical application. CNSL were applied topically for 45 days in the second group of Wistar rats while the first group did not receive any treatment (control) and the third group received Sunflower oil (SFO, positive control). Compared with control and SFO-treated groups, rats exposed to CNSL showed marked reduction in body weight with enlarged liver and altered serum glutamic-pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), urea and creatinine. The lactate dehydrogenase (LDH) was higher along with elevated level of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In contrast, the levels of antioxidant enzymes superoxide dismutase (SOD) and catalase were downregulated. A higher expression of tumor protein P53 and Protein kinase-B or Akt (PKB/Akt) gene followed by comparatively feeble expression of B-cell lymphoma-2 (Bcl2) was detected. Possible interaction of cardanol and cardol with Bcl2-homology domain (BH1 and BH4) of Bcl2 may exhibit inhibitory action following the CNSL exposure. Our study explored that CNSL application on the skin could also develop a metabolic injury with altered oxidative, inflammatory, necrotic and apoptotic status in the affected animals besides skin damage.
Similar content being viewed by others
References
Andonaba, J.B., S.S. Lompo, V. Ouédraogo, F. Ouédraogo, M.S. Ouédraogo, I. Konaté, B. Diallo, and A. Traoré. 2017. Skin damage and aesthetic disadvantage observed in women in the hand craft shelling chain of cashew nuts in a factory to Bobo-Dioulasso, Burkina Faso. Journal of Cosmetics, Dermatological Sciences and Applications 7: 211–220.
Argyris, T.S. 1989. Epidermal tumor promotion by damage in the skin of mice. Progress in Clinical and Biological Research 289: 63–80.
Basu, A., and S. Haldar. 1998. The relationship between BcI2, Bax and p53: Consequences for cell cycle progression and cell death. Molecular Human Reproduction 4: 1099–1109.
Brandt, R.B., J.E. Laux, S.E. Spainhour, and E.S. Kline. 1987. Lactate dehydrogenase in rat mitochondria. Archives of Biochemistry and Biophysics 259: 412–422.
Chen, J. 2016. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harbor Perspectives in Medicine 6: a026104.
Downing, J.G., and S.W. Gurney. 1940. Dermatitis from Cashew Nut Shell Oil. Journal of Industrial Hygiene and Toxicology 22: 169–174.
George, J., and R. Kuttan. 1997. Mutagenic, carcinogenic and cocarcinogenic activity of cashewnut shell liquid. Cancer Letters 112: 11–16.
Hadwan, M.H. 2016. New method for assessment of serum catalase activity. Indian Journal of Science and Technology 9: 1–5.
Hecker, E., W. Adolf, M. Hergenhahn, R. Schmidt, and B. Sorg. 1984. Irritant diterpene ester promoters of mouse skin: contributions to etiologies of environmental cancer and to biochemical mechanisms of carcinogenesis. In Princess Takamatsu Symposia, vol. 14, pp. 3–36.
Hirotani, M., Y. Zhang, N. Fujita, M. Naito, and T. Tsuruo. 1999. NH2-terminal BH4 domain of Bcl-2 is functional for heterodimerization with Bax and inhibition of apoptosis. Journal of Biological Chemistry 274: 20415–20420.
Hishita, T., S. Tada-Oikawa, K. Tohyama, Y. Miura, T. Nishihara, Y. Tohyama, Y. Yoshida, T. Uchiyama, and S. Kawanishi. 2001. Caspase-3 activation by lysosomal enzymes in cytochrome c-independent apoptosis in myelodysplastic syndrome-derived cell line P39. Cancer Research 61: 2878–2884.
Ideo, G., A. Morganti, and N. Dioguardi. 1972. γ-Glutamyl transpeptidase: A clinical and experimental study. Digestion 5: 326–336.
Ji, G., Q. Yang, J. Hao, L. Guo, X. Chen, J. Hu, L. Leng, and Z. Jiang. 2011. Anti-inflammatory effect of genistein on non-alcoholic steatohepatitis rats induced by high fat diet and its potential mechanisms. International Immunopharmacology 11: 762–768.
Kane, D.J., T.A. Sarafian, R. Anton, H. Hahn, E.B. Gralla, J.S. Valentine, T. Örd, and D.E. Bredesen. 1993. Bcl-2 inhibition of neural death: Decreased generation of reactive oxygen species. Science 262: 1274–1277.
Kang, J.H., S.I. Yun, M.H. Park, J.H. Park, S.Y. Jeong, and H.O. Park. 2013. Anti-obesity effect of Lactobacillus gasseri BNR17 in high-sucrose diet-induced obese mice. PLoS ONE 8: e54617.
Lum, G., and S.R. Gambino. 1972. Serum gamma-glutamyl transpeptidase activity as an indicator of disease of liver, pancreas, or bone. Clinical Chemistry 18: 358–362.
Marks, J.G., Jr., T. DeMelfi, M.A. McCarthy, E.J. Witte, N. Castagnoli, W.L. Epstein, and R.C. Aber. 1984. Dermatitis from cashew nuts. Journal of the American Academy of Dermatology 10: 627–631.
Morton, J.F. 1961. The cashew’s brighter future. Economic Botany 15: 57–78.
Offor, S.C.E., E.N. Ukpabi, M.E. Ogbanshi, P.U. Okechukwu, and B.U. Nwali. 2014. The effects of ethanol leaf-extract of Anacardium occidentale on haemoglobin and packed cell volume of albino rats. World Journal of Alternative Medicine 1: 05–08.
Ojeh, O.A. 1981 Production and utilisation of cashewnut shell liquid in Nigeria. Cashew Causerie 9–12.
Okereke, G., O. Emmanuel, V.C. Ude, C.N. Ekweogu, V.O. Ikpeazu, and E.A. Ugbogu. 2020. Physicochemical characteristics, acute and subacute toxicity of cashew nut shell oil in Wistar rats. Scientific African 8: e00391.
Owumi, S.E., J.O. Fatoki, M.A. Gbadegesin, and O.A. Odunola. 2015. Clastogenic and toxicological assessment of cashew (Anacardium occidentale) nut bark extracts in Wistar rats. Acta BiochimicaPolonica 62: 563–567.
Paoletti, F., A. Mocali, and D. Aldinucci. 1990. Superoxide-driven NAD (P) H oxidation induced by EDTA manganese complex and mercaptoethanol. Chemico-Biological Interactions 76: 3–18.
Perveen, H., A. Dey, N.M. Nilavar, G.K. Chandra, S.S. Islam, and S. Chattopadhyay. 2019. Dietary CCPS from bitter gourd attenuates sodium arsenite induced female reproductive ailments cum infertility in wistar rats: Anti-inflammatory and anti-apoptotic role. Food and Chemical Toxicology 131: 110545.
Polasa, K., and C. Rukmini. 1987. Mutagenicity tests of cashewnut shell liquid, rice-bran oil and other vegetable oils using the Salmonella typhimurium/microsome system. Food and Chemical Toxicology 25: 763–766.
Priya, J., L. Ayyasamy, S.M.P. Mahendiran, and A. Selvarathinam. 2021. Occupational safety and health hazards among cashew processing workers of Cuddalore district: A cross-sectional study. Indian Journal of Health Sciences and Biomedical Research (KLEU) 14: 254–259.
Ratner, J.H., S.K. Spencer, and J.M. Grainge. 1974. Cashew nut dermatitis: An example of internal-external contact-type hypersensitivity. Archives of Dermatology 110: 921–923.
Rivadeneyra-Domínguez, E., Y. Becerra-Contreras, A. Vázquez-Luna, R. Díaz-Sobac, and J.F. Rodríguez-Landa. 2018. Alterations of blood chemistry, hepatic and renal function, and blood cytometry in acrylamide-treated rats. Toxicology Reports 5: 1124–1128.
Saitoh, Y., R. Ouchida, A. Kayasuga, and N. Miwa. 2003. Anti-apoptotic defense of bcl-2 gene against hydroperoxide-induced cytotoxicity together with suppressed lipid peroxidation, enhanced ascorbate uptake, and upregulated Bcl-2 protein. Journal of Cellular Biochemistry 89: 321–334.
Seo, J.B., S.S. Choe, H.W. Jeong, S.W. Park, H.J. Shin, S.M. Choi, J.Y. Park, E.W. Choi, J.B. Kim, D.S. Seen, and J.Y. Jeong. 2011. Anti-obesity effects of Lysimachia foenum-graecum characterized by decreased adipogenesis and regulated lipid metabolism. Experimental & Molecular Medicine 43: 205–215.
Shamas-Din, A., J. Kale, B. Leber, and D.W. Andrews. 2013. Mechanisms of action of Bcl-2 family proteins. Cold Spring Harbor Perspectives in Biology 5: a008714.
Slack, A., A. Yeoman, and J. Wendon. 2010. Renal dysfunction in chronic liver disease. Critical Care 14: 1–10.
Sullivan, J.T., C.S. Richards, H.A. Lloyd, and G. Krishna. 1982. Anacardic acid: Molluscicide in cashew nut shell liquid. Planta Medica 44: 175–177.
Susnow, N., L. Zeng, D. Margineantu, and D.M. Hockenbery. 2009. Bcl-2 family proteins as regulators of oxidative stress. In Seminars in cancer biology 19: 42–49. Academic Press.
Takabatake, T., H. Ohta, Y.I. Ishida, H. Hara, Y. Ushiogi, and N. Hattori. 1988. Low serum creatinine levels in severe hepatic disease. Archives of Internal Medicine 148: 1313–1315.
Tan, S., B. Gao, Y. Tao, J. Guo, and Z.Q. Su. 2014. Antiobese effects of capsaicin–chitosan microsphere (CCMS) in obese rats induced by high fat diet. Journal of Agricultural and Food Chemistry 62: 1866–1874.
Trosko, J.E. 2003. The role of stem cells and gap junctional intercellular communication in carcinogenesis. BMB Reports 36: 43–48.
Varghese, I., R. Rajendran, C.K. Sugathan, and T. Vijayakumar. 1986. Prevalence of oral submucous fibrosis among the cashew workers of Kerala-south India. Indian Journal of Cancer 23: 101–104.
Weydert, C.J., and J.J. Cullen. 2010. Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nature Protocols 5: 51–66.
Yang, Y., G. Jiang, P. Zhang, and J. Fan. 2015. Programmed cell death and its role in inflammation. Military Medical Research 2: 1–12.
Yin, X.M., Z.N. Oltvai, and S.J. Korsmeyer. 1994. BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature 369: 321–323.
Acknowledgements
We are sincerely grateful to the Maa Durga Cashew Processing industry for providing CNSL free of cost for this experiment.
Author information
Authors and Affiliations
Contributions
Animal treatment, biochemical test and histology were performed by AS and IS. Native gel elctrophoresis and PCR were performed by AD and SM. Status of inflammatory markers were measured by SD. Molecular docking were analyzed by AG. Experimental protocol design and manuscript writing were done by SC and SKD.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no financial or non-financial conflict of interest.
Ethical Approval
Approved by IAEC (Institutional Animal Ethics Committee) Approval No—VU/IAEC-I/SC-2/3-14/19.
Consent to Publish
The authors have agreed and approved the submitted version of the manuscript.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Sahoo, A., Ghosh, A., Dey, A. et al. Assessment of Oxidative Liver Injury Caused by Cashew Nut Shell Liquid (CNSL) via Interacting with Bcl2 Gene in Male Wistar Rats and Basic In-silico Approaches. Proc Zool Soc 77, 136–146 (2024). https://doi.org/10.1007/s12595-024-00516-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12595-024-00516-6