Impact of omega 3 alone or in combination with irinotecan on bone marrow and spleen of rats: in vivo study


  • Alaa Radhi Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Iraq
  • Nada Al-Shawi
  • Ali Hassan



Keywords: Omega-3 fish oil, Irinotecan, Bone Marrow, Spleen, and Mitotic Index.



Objectives: The present study designed to explore the genotoxicity through measurement of Mitotic index in bone marrow and the spleen cells, as possible mechanism of bone marrow and spleen toxicity that induced by irinotecan; and to describe the protective actions of omega 3 against irinotecan induced genotoxicity in bone marrow and the spleen of rats.

Methods: Twenty four (24) rats (Sprague-Dawley) were randomly divided into four groups: Group Ӏ, rats  received single oral daily dose of distilled water (2 ml/kg) for 25 days (negative control group); Group ӀӀ (irinotecan-treated), received single daily oral dose of (2 ml/kg) distilled water for 25 days by the oral gavage and subsequently received irinotecan (50mg/kg) on days: 5, 10, 15 (total dose=150 mg/kg) by intraperitoneal injection; Group ӀӀӀ, received oral dose of Omega-3 fish oil (600mg/kg/day) daily for 25 successive days by oral gavage (Omega-3 fish oil-treated); Group ӀV (Omega-3 fish oil + irinotecan), received oral dose of Omega-3 fish oil (600mg/ kg/ day) given daily for 25 successive days by oral gavage, and received subsequently irinotecan (50mg / kg body weight) on days: 5, 10, 15 (total dose=150 mg/kg) by intraperitoneal injection.

Results: Mitotic index in the Bone Marrow and in the Spleen Cells were shown to be significantly decreased (p<0.05) in rats treated with irinotecan (group ІІ) compared to corresponding levels in the negative control group (Group I) of the rats; Orally administered Omega-3 fish oil with total cumulative dose of irinotecan (Group IV), resulted in significant elevation (P<0.05) of the Mitotic index in bone marrow and the spleen cells compared to corresponding levels in rats treated with irinotecan (group ІІ).

Conclusion: Results of current study suggested that the administration of Omega-3 fish oil could be useful supplements that may alleviate irinotecan induced genotoxicity through the elevation of mitotic indices in bone marrow and the spleen cells of the rats; but, in mild level.



Jinsheng Yu, William D. Shannon, Mark A. Watson, and Howard L. McLeod. Gene Expression Profiling of the Irinotecan Pathway in Colorectal Cancer. Clinical Cancer Research. 2005; 11: 2053–2062.

Femke M. de Man, Andrew K. L. Goey, Ron H. N. van Schaik, Ron H. J. Mathijssen, Sander Bins. Individualization of Irinotecan Treatment: A Review of Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics. Clin Pharmacokinet. 2018; 57: 1229–1254.

Mathijssen RH, van Alphen RJ, Verweij J, et al. Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res. 2001; 7: 2182– 2194.

Xun Bao, Jianmei Wu, Seongho Kim, Patricia Lo Russo, DO2, Jing Li. Pharmacometabolomics Reveals Irinotecan Mechanism of Action in Cancer Patients. The Journal of Clinical Pharmacology. 2019; 59 (1): 20–3.

Weller S, Braun MC, Tan BK, et al. Human blood IgM “memory” B cells are circulating splenic marginal zone B cells harboring a prediversifi ed immunoglobulin repertoire. Blood. 2004; 104: 3647–3654.

E.A.Miles and P.C.Caldery. “Influence ofmarine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis”. British Journal of Nutrition. 2012; 107: S171– S184.

W. Xin, W. Wei, and X. Li. “Effects of fish oil supplementation on cardiac function in chronic heart failure: a meta-analysis of randomized controlled trials”. Heart. 2012; 98 (22): 1620-1625.

S. Car and R. Webel. “Fish oil supplementation & coronary artery disease: does it help?”. Missouri Medicine. 2012; 109 (2): 142–145.

R. S. Chapkin, W. Kim, J. R. Lupton, and D. N. McMurray. “Dietary docosahexaenoic and eicosapentaenoic acid: emerging mediators of inflammation,” Prostaglandins Leukotrienes and Essential Fatty Acids. 2009; 81: 187–191.

P.C.Calder. “Immunomodulation by omega-3 fatty acids,” Prostaglandins Leukotrienes and Essential Fatty Acids. 2007; 77: 327–335.

Rudkowska. “Fish oils for cardiovascular disease: impact on diabetes”. Maturitas. 2010; 67: 25–28.

V. C. Vaughan, M. R. Hassing, and P.A. Lewandowski. “Marine polyunsaturated fatty

acids and cancer therapy”. British Journal of Cancer. 2013; 108 (3): 486–492.

J. Cockbain, G. J. Toogood, and M. A. Hull. “Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer”. Gut. 2012; 61 (1): 135–149.

Nicolò Merendino, Lara Costantini, LauraManzi, RominaMolinari, Donatella D’Eliseo, and Francesca Velotti. Dietary w-3 Polyunsaturated Fatty Acid DHA: A Potential Adjuvant in the Treatment of Cancer. BioMed Research International. 2013; 2013: 310186 (11 pages).

Melinda E Varney, W Elaine Hardman and Vincent E Sollars. Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation. Lipids in Health and Disease. 2009; 8: 9-15.

WE Hardman, MP Moyer and IL Cameron. Consumption of an omega-3 fatty acids product, INCELL AAFATM, reduced side-effects of CPT-11 (irinotecan) in mice. British Journal of Cancer. 2002; 86: 983 – 988.

Alaa Radhi K, Nada N. Al-Shawi. Possible Protective Effects of high- versus low- dose of lutein in combination with irinotecan on Liver of Rats: Role of Oxidative Stress and Apoptosis. Indian Journal of Forensic Medicine & Toxicology. 2021; 15 (1): 2439- 2445.