Attenuation of cisplatin induced myelosuppression by methanol extract of Cedrus deodara in Wistar rats

Dindukurthi Harinathbabu Sushmitha; Channaiah Ramesh; Belladamadagu Appajappa Sowmya; Byrojai Rao Sushma Bai; Pinkey Rawal; Shafi Ulla Khan Shabana

doi:10.1515/jcim-2021-0515

Article

Attenuation of cisplatin induced myelosuppression by methanol extract of Cedrus deodara in Wistar rats

Dindukurthi Harinathbabu Sushmitha , Channaiah Ramesh , Belladamadagu Appajappa Sowmya , Byrojai Rao Sushma Bai , Pinkey Rawal and Shafi Ulla Khan Shabana

Published/Copyright: March 24, 2022

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From the journal Journal of Complementary and Integrative Medicine Volume 19 Issue 4

Abstract

Objective

The present study was performed to evaluate the protective effects of methanol extract of Cedrus deodara against cisplatin induced.

Methods

Myelosuppression in albino Wistar rats. All experimental animals were administered with cisplatin on 1st, 3rd, 5th and 7th day to induce bone marrow toxicity and rats were treated with methanol extract of C. deodara for 21 days. Blood samples were collected from all the animals on day 1st, 7th, 14th and 21st after 1 h before the administration of the drugs and hematological parameters like RBC, WBC, platelets, hemoglobin, hematocrit, eosinophils, basophils, neutrophils, lymphocytes, bleeding time and clotting time were determined were determined. At 21st, all rats were sacrificed and bone marrow samples were collected. The part of bone marrow samples was used for the determination of antioxidant enzymes and remaining were subjected to histopathological examination.

Results

The animals of therapeutic groups administered with extract of C. deodara have exhibited significant rise in hematological parameters and shorten bleeding time and clotting time when compare to toxic control animals on the day 14 and day 21. The histopathological examination revealed the regeneration of bone marrow cells in the extract treated animals. There was significant reduction in lipid peroxidation and increase in antioxidant enzymes was found in extract treated animals.

Conclusions

The methanol extract of C. deodara of have shown significant protective effects against cisplatin induced myelosuppression in albino Wistar rats.

Keywords: antioxidant enzymes; Cedrus deodara ; cisplatin; glutathione peroxidase; hematological parameter; lipid peroxidation; myelosuppression

Corresponding author: Dr. Channaiah Ramesh, Professor & Head, Department of Pharmacology, East West College of Pharmacy, No-63, I Bhartah Nagar, Off Magadi Road, Vishwaneedam (PO), Bangalore, 560091, India, Mobile: +91-9901514401, E-mail: rameshcology80@gmail.com

Acknowledgments

The authors of manuscript are thankful to the principal and management of East West College of Pharmacy, Bangalore for providing facilities to conduct this research work.

Author contributions: All the authors were equally involved in every phase of research work present research work and given their consent to submit the present manuscript for the publication in your esteemed journal.
Competing interests: Authors state no conflict of interest.
Informed consent: Not applicable.
Ethical approval: The experimental protocol was approved by IAEC, East West College of Pharmacy, Bangalore and conducted strictly according to ethical principles prescribed by CBCSEA, New Delhi.

References

1. Kulmira, N, Thomas, JR, Raquel, A. Editorial: adverse effects of cancer chemotherapy: anything new to improve tolerance and reduce sequelae?. Front Pharmacol 2018;9:1–3.10.3389/fphar.2018.00245Search in Google Scholar

2. Ozben, T. Oxidative stress and apoptosis: impact on cancer therapy. J Pharm Sci 2007;96:2181–96. https://doi.org/10.1002/jps.20874.Search in Google Scholar PubMed

3. Conklin, KA. Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr Cancer Ther 2004;3:294–300. https://doi.org/10.1177/1534735404270335.Search in Google Scholar PubMed

4. Mi Rim, C, Craig, AS, Victoria, MC, Anne, HB, John, HP, Richard, B, et al.. Granulocyte colony-stimulating factor (G-CSF) patterns of use in cancer patients receiving myelosuppressive chemotherapy. Support Care Cancer 2014;22:1619–28.10.1007/s00520-014-2121-7Search in Google Scholar PubMed

5. Seymour, P. Reduction of Toxicity in Cancer Chemotherapy. Cancer Res 2009;29:2319–25.Search in Google Scholar

6. Aleksandra, T, Paula, M, Jakub, F. Triphala: current applications and new perspectives on the treatment of functional gastrointestinal disorders. Chin Med 2018;39:1–11.Search in Google Scholar

7. Christine, TP, Kate, D, Deepak, C. Therapeutic Uses of Triphala in Ayurvedic Medicine. J Alt and Compl Med 2017;23:607–14.10.1089/acm.2017.0083Search in Google Scholar PubMed PubMed Central

8. Dhananjaya, S, Aparna, K. Current status of cancer burden: Global and Indian scenario. Biomed Res J 2014;1:1–5. https://doi.org/10.1177/1534735404270335.Search in Google Scholar

9. Amrendra Kumar, C, Shamim, A, Avijit, M. Cedrus deodara (Roxb.) Loud.: A Review on its Ethnobotany, Phytochemical and Pharmacological Profile. Pharmacognosy J 2011;23:12–7.10.5530/pj.2011.23.2Search in Google Scholar

10. Sumeet, G, Anu, W, Rajat, M. Phytochemistry and pharmacology of Cedrus deodara: an overview. J Alternative Compl Med 2011;2:2010–14.Search in Google Scholar

11. Kokate, CK. Practical pharmacognosy. New Delhi: Vallabh Prakashan; 1994, vol. 4:100–14 pp.Search in Google Scholar

12. Khandelwal, KR. Practical pharmacognosy-techniques and experiments. Pune: Nirali Prakashan; 2000.Search in Google Scholar

13. Singleton, VL, Orthofer, R, Lamuela-Raventos, RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of Foline Ciocalteu reagent. Methods Enzymol 1999;299:152–78. https://doi.org/10.1016/s0076-6879(99)99017-1.Search in Google Scholar

14. Harborne, JB. Phytochemical methods: a guide to modern techniques of plant analysis, 3rd ed. New York: Chapman and Hall; 1998.Search in Google Scholar

15. Shyh-Horng, L, Ming-Han, L, Kai-An, C, Ni-Hsuan, L, Chih-Hsuan, C, Hsin-Chieh, W, et al.. Chlorella sorokiniana extract prevents cisplatin-induced myelotoxicity in vitro and in vivo. Oxid Med Cell Longev 2020;13:1–14.Search in Google Scholar

16. Oluwatoyin, AA, Emmanuel, OE. Hematological effects of repeated graded doses of the methanol extract of Paullinia pinnata (Linn.) leaves in Wistar albino rats. Pharmacognosy Res 2015;7:34–8.10.4103/0974-8490.150522Search in Google Scholar PubMed PubMed Central

17. Ismail, K, Abdurrahim, K, Ataman, G, Erkan, A, Mustafa, D. The protective effect of naringenin-oxime on cisplatin-induced toxicity in rats. Biochem Res Int 2017;8:1–9.10.1155/2017/9478958Search in Google Scholar

18. Sanjiv, K, Jagadish, VK. Effect of daidzein on cisplatin-induced hematotoxicity and hepatotoxicity in experimental rats. Indian J Pharmacol 2017;49:49–54.10.4103/0253-7613.201022Search in Google Scholar

19. Hao, G, Yu, GY, Gu, B, Tan, J. Theory and practice of histological techniques edited by J.D. Bancroft & A. Stevens, Churchill Livingstone, Edinburgh, 740 pages, £55.00. Histopathology 1990;17:386.10.1111/j.1365-2559.1990.tb00755.xSearch in Google Scholar

20. Shankar, T, Downie, SC, Anupama, BK. Protective effect of alpha-lipoic acid against lead acetate-induced oxidative stress in the bone marrow of rats. Int J Pharmacol 2011;7:217–27.10.3923/ijp.2011.217.227Search in Google Scholar

21. Chance, B, Maehly, AC. Assay of catalase and peroxidases. Enzymologia 1955;11:764–75. https://doi.org/10.1016/s0076-6879(55)02300-8.Search in Google Scholar

22. Kakkar, P, Das, B, Viswanathan, PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 1984;21:130–2.Search in Google Scholar

23. Habig, WH, Pabst, MJ, Jakoby, WB. Glutathione-S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130–9. https://doi.org/10.1016/s0021-9258(19)42083-8.Search in Google Scholar

24. Carlberg, I, Mannervik, EB. Glutathione level in rat brain. J Biol Chem 1975;250:4475–80. https://doi.org/10.1016/s0021-9258(19)41206-4.Search in Google Scholar

25. Mohandas, J, Marshal, 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;33:1801–7. https://doi.org/10.1016/0006-2952(84)90353-8.Search in Google Scholar PubMed

26. Ellman, GL, Courtney, KD, Andres, V, Featherstone, RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88–95. https://doi.org/10.1016/0006-2952(61)90145-9.Search in Google Scholar PubMed

27. Curtis, CH. Physical carcinogenesis: advances and perspectives for the 1990s. Cancer Res 1991;51:5023–44.Search in Google Scholar

28. Tripathi, KD. Chemotherapy of neoplastic diseases. In: Tripathi, M, editor. Essentials of medicinal pharmacology, 6th ed. New Delhi; 2008:819–34 pp.10.5005/jp/books/10510_13Search in Google Scholar

29. Das, B, Antoon, R, Tsuchida, R, Lotfi, S., Morozova, O., Farhat, W., et al.. Squalene selectively protects mouse bone marrow progenitors against cisplatin and carboplatininduced cytotoxicity in vivo without protecting tumor growth. Neoplasia 2008;10:1105–19. https://doi.org/10.1593/neo.08466.Search in Google Scholar PubMed PubMed Central

30. Basu, A, Ghosh, P, Bhattacharjee, A, Patra, AR, Bhattacharya, S. Prevention of myelosuppression and genotoxicity induced by cisplatin in murine bone marrow cells: effect of an organovanadium compound vanadium(III)-l-cysteine. Mutagenesis 2015;30:509–17. https://doi.org/10.1093/mutage/gev011.Search in Google Scholar PubMed PubMed Central

31. Tiwari, AK, Srinivas, PV, Kumar, SP, Rao, JM. Free radical scavenging active components from Cedrus deodara. J Agric Food Chem 2001;49:4642–5. https://doi.org/10.1021/jf010573a.Search in Google Scholar PubMed

32. Ajay, K, Renuka, S, Madhulika, B. Bioactive potential of Cedrus deodara (Roxb.) Loud essential oil (bark) against Curvularia lunata and molecular docking studies. SN Appl Sci 2020;2:1045.10.1007/s42452-020-2837-6Search in Google Scholar

Received: 2021-11-12

Accepted: 2022-02-13

Published Online: 2022-03-24

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Articles in the same Issue

https://doi.org/10.1515/jcim-2021-0515

Keywords for this article

antioxidant enzymes; Cedrus deodara; cisplatin; glutathione peroxidase; hematological parameter; lipid peroxidation; myelosuppression