LD50 and affective dose of Eruca sativa mill (gergeer) ethanolic extract

  • Rana Abdulla Salih
  • Zuhair Abdulkareem. Dawah


Cardiotoxicity is defined as drug-induced damage to the heart muscle, which can result in cardiac failure or cardiac arrest. Cardiotoxicity is a common side effect of traditional anticancer drugs such as doxorubicin, taxanes, 5-fluorouracil, and cyclophosphamide, as well as newer agents such as biological antibodies such as Nivo. Cardiotoxicity is also caused by the long-term use of neurologic/psychiatric medications. This study was designed to determine the effect of eruca sativa mill (Gergeer) leaves extract on cardiotoxicity induced by doxorubicin in rabbits. The fifty-four rabbits used in this study were obtained from a local rabbit breeder. Animals ranged between 1-1.3 years old, and their weight was approximately 1-2kg without specifying gender experiment Acute toxicity study, The pilot study to determine the LD50 dose of Eruca sativa mill (gergeer) by "up and down" method after acute exposure in rabbits, The effective dose of Eruca sativa mill (gergeer) was determined by using a simple line equation. The effective dose of Eruca sativa. troponin I determine the level of  proteins in the blood increase in heart attack,.The Troponin-I level of the control positive group revealed a significant increase as compared with G3, G4, G5, and the control negative group.The cTn-I level of the G3 significant increase is compared with treated G4,G5 group and control negative group with a significant decrease  is compared with G1, G2 group and control positive group ; while treated G4 ,G5 group significant decrease  is compared with treated G1,G2,G3 group and control positive, Log number dose-response curve and maximum effective dose the simple line equation revealed that the effective Eruca sativa dose of Troponin I level was (3.01 , 2.99 ,1.97 ,1.015, 1.030) (ng/ml) respectively, whereas the effective Eruca  sativa dose of Troponin I was 316 mg/kg. conclusion , The effective dose-response results asymptotic to 10 % of LD50, induced cardiac toxicity with DOX appear biochemically, cardiographycally and histopathologically, The Eruca sativa mill (gergeer) extract was effective protective for induced cardiac toxicity.


1. Abbas, N. A. T., and Kabil, S. L. (2017). Pentoxifylline and Cilostazol Against Rat Heart Injuries Induced by Doxorubicin. Egyptian Journal of Basic and Clinical Pharmacology, 7(1), 47–56.
2. AlMalki, W. H., and Shahid, I. (2020). Characterization of antihypertensive and cardioprotective effects of extra virgin olive oil against doxorubicin induced cardiomyopathy in rats. Journal of Pharmacy and Pharmacognosy Research, 8(4), 316–326.
3. AL-OKaily,B.N.; AL-Haddad,A.A and Salman,A.D.(2013). Effect of Different Doses of Doxorubicin on pituitary Gland and some Testicular function in adults Male Rabbits. The Iraqi Journal of Veterinary medicine, 37C1):121-128
4. Alotaibi, B., El-Masry, T. A., Tousson, E., Alarfaj, S. J., & Saleh, A. (2020). Therapeutic effect of rocket seeds (Eruca sativa L.) against hydroxyapatite nanoparticles injection induced cardiac toxicity in rats. Pak. J. Pharm. Sci, 33(4), 1839-1845.‏
5. Awadelkareem, A. M., Al-Shammari, E., Elkhalifa, A. E. O., Adnan, M., Siddiqui, A. J., Snoussi, M., ... & Ashraf, S. A. (2022). Phytochemical and In Silico ADME/Tox Analysis of Eruca sativa Extract with Antioxidant, Antibacterial and Anticancer Potential against Caco-2 and HCT-116 Colorectal Carcinoma Cell Lines. Molecules, 27(4), 1409.‏
6. Bennett, R. N., Rosa, E. A., Mellon, F. A., & Kroon, P. A. (2006). Ontogenic profiling of glucosinolates, flavonoids, and other secondary metabolites in Eruca sativa (salad rocket), Diplotaxis erucoides (wall rocket), Diplotaxis tenuifolia (wild rocket), and Bunias orientalis (Turkish rocket). Journal of agricultural and food chemistry, 54(11), 4005-4015.‏
7. Dixon, W. J. (1965). The "Up and Down" method for small samples. American Statistical Association Journal, P. 967-978.
8. Fadillioglu, E., Oztas, E., Erdogan, H., Yagmurca, M., Sogut, S., Ucar, M., and Irmak, M. K. (2004). Protective effects of caffeic acid phenethyl ester on doxorubicin‐induced cardiotoxicity in rats. Journal of Applied Toxicology: An International Journal, 24(1), 47–52.
9. Gupta, M., Kaur, H., G. Singhal, K., and K. Gupta, V. (2019). Evaluation of avena sativa seeds extract as cardioprotective agent in rats. IP International Journal of Comprehensive and Advanced Pharmacology, 4(2), 39–47.
10. Hadi, M. A., Almamoori, A. M., Al-Hassnawi, A. T., & Hameedi, E. H. (2017). Oxidative response associated with treatment of male Albino rats with Eruca sativa Mill leaves extract and correlations with complete blood picture. Journal of Pharmaceutical Sciences and Research, 9(11), 2278-2285.‏
11. Hammami, I. et al. (2019) ‘Protective Action of Eruca sativa Leaves Aqueous Extracts Against Bisphenol A-Caused In Vivo Testicular Damages’, 00(0), pp. 1–11.
12. Heimler, D., Isolani, L., Vignolini, P., Tombelli, S., & Romani, A. (2007). Polyphenol content and antioxidative activity in some species of freshly consumed salads. Journal of Agricultural and Food Chemistry, 55(5), 1724-1729.‏
13. Jin, J.; Koroleva, O.A.; Gibson, T.; Swanston, J. and Magan, J. et al., (2009). Analysis of phytochemical composition and chemoprotective capacity of rocket (Eruca sativa and Diplotaxis tenuifolia) leafy salad following cultivation in different environments. J. Agric. Food Chem., 57(12): 5227-5234.
14. Johnson-Arbor, K., and Dubey, R. (2017). Doxorubicin.
15. Kancharlapalli, S., Sweeya, P. S., Gandham, A. P. D., and Rao, V. U. M. (2014). CARDIOTOXICITY AND USE OF HERBAL DRUGS- A REVIEW. Asian Journal of Pharmaceutical Research and Development, 2(1), 1–9.
16. Martín-Peláez, S., Castañer, O., Konstantinidou, V., Subirana, I., Muñoz-Aguayo, D., Blanchart, G., Gaixas, S., de la Torre, R., Farré, M., and Sáez, G. T. (2017). Effect of olive oil phenolic compounds on the expression of blood pressure-related genes in healthy individuals. European Journal of Nutrition, 56(2), 663–670.
17. Nowfel, A.J. (2015) ‘Role of alcoholic extract of Roket ( Eruca sativa ) leaves on male reproduction of experimentally induced-oxidative stressed rats’, 39(2), pp. 47–54.
18. Oliveira, P. J., Bjork, J. A., Santos, M. S., Leino, R. L., Froberg, M. K., Moreno, A. J., & Wallace, K. B. (2004). Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity. Toxicology and applied pharmacology, 200(2), 159-168.‏
19. Rockley, K. (2018). In Vitro Evaluation of Anthracycline-induced Cardiotoxicity and Mitigation by Perturbation of Angiotensin Signalling (Doctoral dissertation, Durham University).
20. Salim, A.G. (2021) ‘Effect of Avena Sativa Seeds Ethanolic Extract and Enalapril Alone and Combined on Induced Cardiotoxicity by Doxorubicin in Adult Female Rats’.
21. Shaker, R. A., Abboud, S. H., Assad, H. C., and Hadi, N. (2018). Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. BMC Pharmacology and Toxicology, 19(1), 1-10.
22. Singh, R., De, S., and Belkheir, A. (2013b). Avena sativa (Oat), A Potential Neutraceutical and Therapeutic Agent: An Overview. Critical Reviews in Food Science and Nutrition, 53(2), 126-144.
23. Taleb, A., Ahmad, K. A., Ihsan, A. U., Qu, J., Lin, N., Hezam, K., Koju, N., Hui, L., and Qilong, D. (2018). Antioxidant effects and mechanism of silymarin in oxidative stress induced cardiovascular diseases. Biomedicine and Pharmacotherapy, 102, 689–698.
24. Thippeswamy, A. H. M., Shirodkar, A., Koti, B. C., Sadiq, A. J., Praveen, D. M., Swamy, A. H. M. V., and Patil, M. (2011). Protective role of Phyllantus niruri extract in doxorubicin-induced myocardial toxicity in rats. Indian Journal of Pharmacology, 43(1), 31.
25. Wallace, K. B., Hausner, E., Herman, E., Holt, G. D., MacGregor, J. T., Metz, A. L., Murphy, E., Rosenblum, I. Y., Sistare, F. D., and York, M. J. (2004). Serum Troponins as Biomarkers of Drug-Induced Cardiac Toxicity. Toxicologic Pathology, 32(1), 106–121.
26. Weli, S. M., Kareem, S. I., Shareef, O. H., Rauf, H. G., Raouf, C. G., & Hama, A. A. (2021). The effects of the aqueous extract of the leaves of the local plant eruca sativa on lipid profile and some minerals in the blood of male white mice. Iraqi Journal of Science, 62(4), 1088–1093.