Biochemical and Molecular Studies on the Role of Rosemary (Rosmarinus officinalis) Extract in Reducing Liver and Kidney Toxicity Due to Etoposide in Male Rats

Main Article Content

Majd Almakhatreh
Ezar Hafez
Ehab Tousson
Ahmed Masoud


Aims: Etoposide (Vepesid) is chemotherapeutic drugs that inhibit topoisomerase II activity and long been used for treatment of human malignancies, where it is a semi-synthetic compound derived from the plant Podophyllum peltatum. The current study was designed to investigate the possible protective effect of rosemary extract against Etoposide -induced changes in liver and kidney functions, and DNA damage in rats.

Materials and Methods: A total of 50 male Wistar albino rats were divided randomly into four groups (1st group was control; 2nd group was treated with rosemary, 3rd group was received etoposide, and 4th & 5th groups was co- and post treated groups respectively).

Results: The administration of Etoposide revealed a significant increase in serum ALT, AST, ALP, creatinine, urea, potassium ions, chloride ions, and DNA damage. In contrast; a significant decrease in albumen, total proteins, sodium ions, and calcium ions were when compared with control group. This increased in ALT, AST, ALP, creatinine, urea, potassium ions, chloride ions, and DNA damage was reduced after administration of rosemary when co-treated with etoposide (G4), or post-treated after etoposide  (G5) for four weeks with lowest damage in G4. Also, this decreased in albumen, total proteins, sodium ions, and calcium ions was increased after administration of rosemary when co-treated with etoposide (G4), or post-treated after etoposide (G5) for four weeks with lowest damage in G4.

Conclusion: It could be concluded that rosemary has a promising role and it worth to be considered as a natural substance for protective the liver and kidney toxicity induced by etoposide (Vepesid) chemotherapy.

Chemotherapy, liver, kidney, rat, rosemary, etoposide

Article Details

How to Cite
Almakhatreh, M., Hafez, E., Tousson, E., & Masoud, A. (2019). Biochemical and Molecular Studies on the Role of Rosemary (Rosmarinus officinalis) Extract in Reducing Liver and Kidney Toxicity Due to Etoposide in Male Rats. Asian Journal of Research in Medical and Pharmaceutical Sciences, 7(4), 1-11.
Original Research Article


Tousson E, Atteya Z, El-Atrash E, Jeweely OI. Abrogation by Ginkgo biloba leaf extract on hepatic and renal toxicity induced by methotrexate in rats. J Cancer Res Treat. 2014;2(3):44-51.

Tousson E, Hafez E, Zaki S, Gad A. P53, Bcl-2 and CD68 expression in response to amethopterin-induced lung injury and ameliorating role of l-carnitine. Biomedicine & Pharmacotherapy. 2014; 68(5):631-9.

Tousson E, Hegazy M, Hafez E, Ahmed EA. The effect of L-carnitine on amethopterin-induced toxicity in rat large intestine. J Cancer Res Treat. 2014;2(3): 55-63.

Tousson E, Zaki ZT, Abu-Shaeir WA, Hassan H. Methotrexate-induced hepatic and renal toxicity: Role of L-carnitine in treatment. Biomed Biotechnol. 2014;2(4): 85-92.

Tousson E, Hafez E, Zaki S, Gad A. The cardioprotective effects of L-carnitine on rat cardiac injury, apoptosis, and oxidative stress caused by amethopterin. Environmental Science and Pollution Research. 2016;23(20):20600-8.

Basuony M, Hafez E, Tousson E, Massoud A, Elsomkhraty S, Eldakamawy S. Beneficial role of Panax ginseng root aqueous extract against Cisplatin induced blood toxicity in rats. Am J Biol Chem. 2015;3(1):1-7.

Al-Rasheed NM, El-Masry TA, Tousson E, Hassan HM, Al-Ghadeer A. Hepatic protective effect of grape seed proanthocyanidin extract against Gleevec-induced apoptosis, liver Injury and Ki67 alterations in rats. Brazilian Journal of Pharmaceutical Sciences. 2018;54(2). e17391.

Al-Rasheed NM, El-Masry TA, Tousson E, Hassan HM, Al-Ghadeer A. Protective potential of grape seed proanthocyandins extract against Glivec (Imatinib mesylate) induced liver toxicity and oxidative stress in male rats. Annual Research & Review in Biology. 2017;20(6):1-9.

Shin HJ, Kwon HK, Lee JH, Anwar MA, Choi S. Etoposide induced cytotoxicity mediated by ROS and ERK in human kidney proximal tubule cells. Scientific Reports. 2016;6:1-13.

Tousson E, Bayomy MF, Ahmed AA. Rosemary extract modulates fertility potential, DNA fragmentation, injury, KI67 and P53 alterations induced by etoposide in rat testes. Biomedicine & Pharmacotherapy. 2018;98:769-74.

El-Moghazy M, Zedan NS, El-Atrsh AM, El-Gogary M, Tousson E. The possible effect of diets containing fish oil (omega-3) on hematological, biochemical and histopathogical alterations of rabbit liver and kidney. Biomedicine & Preventive Nutrition. 2014;4(3):371-7.

Tousson E, Alghabban AJ, Harga HA. Thyroidectomy induced hepatic toxicity and possible amelioration by Ginkgo biloba leaf extract. Biomedicine & Preventive Nutrition. 2014;4(3):391-7.

Saggu S, Sakeran MI, Zidan N, Tousson E, Mohan A, Rehman H. Ameliorating effect of chicory (Chichorium intybus L.) fruit extract against 4-tert-octylphenol induced liver injury and oxidative stress in male rats. Food and Chemical Toxicol. 2014;72:138-146.

Salama AF, Tousson E, Elfetoh EM, Elhaak M, Elawni M. Effect of Egyptian plant Silybum marianum on the kidney during the treatment of liver fibrosis in female albino rats induced by alcohol in comparison to the medical silymarin from China. Intern J Current Microbiology and Applied Ssciences. 2015;4(3):557-70.

Elmasry TA, Al-Shaalan NH, Tousson E, El-Morshedy K, Al-Ghadeer A. Star anise extracts modulation of reproductive parameters, fertility potential and DNA fragmentation induced by growth promoter Equigan in rat testes. Brazilian Journal of Pharmaceutical Sciences. 2018;54(1).

Abd Eldaim MA, Tousson E, El Sayed IE, Awd WM. Ameliorative effects of Saussurea lappa root aqueous extract against Ethephon‐induced reproductive toxicity in male rats. Environmental Toxicol. 2019;34(2):150-9.

Oyouni AA, Saggu S, Tousson E, Mohan A, Farasani A. Mitochondrial nephrotoxicity induced by tacrolimus (FK-506) and modulatory effects of Bacopa monnieri (Farafakh) of Tabuk Region. Pharmacognosy Research. 2019;11(1):20.

Oyouni AA, Saggu S, Tousson E, Rehman H. Immunosuppressant drug tacrolimus induced mitochondrial nephrotoxicity, modified PCNA and Bcl-2 expression attenuated by Ocimum basilicum L. in CD1 mice. Toxicology Reports. 2018;5:687-94.

Aldubayan MA, Elgharabawy RM, Ahmed AS, Tousson E. Antineoplastic activity and curative role of Avenanthramides against the growth of Ehrlich solid tumors in mice. Oxidative Medicine and Cellular Longevity; 2019. ID 5162687, 12 pages.

Gad AS, EL‐SALAM MH. The antioxidant properties of skim milk supplemented with rosemary and green tea extracts in response to pasteurisation, homogenisation and the addition of salts. International Journal of Dairy Technology. 2010;63(3):349-55.

Akela MA, El Atrash AM, El Kilany MI, Tousson E. Qualitative and quantitative characterization of biologically active compounds of Rosemary (Rosmarinus officinalis) Leaf Extract. Journal of Advanced Trends in Basic and Applied Science. 2018;2(1):59-64.

Habtemariam, S. The therapeutic potential of rosemary (Rosmarinus officinalis) diterpenes for Alzheimer’s disease. Evidence-Based Complementary and Alternative Medicine. 2016;1-14.

Tousson E, El-Moghazy M, Massoud A, El-Atrash A, Sweef O, Akel A. Physiological and biochemical changes after boldenone injection in adult rabbits. Toxicology and Industrial Health. 2016;32(1):177-82.

Tousson E, Keshta AT, Hussein Y, Fekry RM, Abo-Ghaneima WK. Renal protective effect of Ginkgo biloba and L-carnitine Extracts against Pentylenetetrazol Induced Toxicity, Oxidative Stress, Injury and Proliferation Alternation in Epileptic Rats. Annual Research & Review in Biology. 2019;28:1-3.

Bolkiny Y, Tousson E, El-Atrsh A, Akela M, Farg E. Costus root extract alleviates blood biochemical derangements of experimentally-induced hypo-and hyperthyroidism in mice. Annual Research & Review in Biology. 2019;31(5):1-0.

Tousson E, El-Moghazy M, El-Atrsh E. The possible effect of diets containing Nigella sativa and Thymus vulgaris on blood parameters and some organs structure in rabbit. Toxicology and Industrial Health. 2011;27(2):107-16.

Salama AF, Kasem SM, Tousson E, Elsisy MK. Protective role of L-carnitine and vitamin E on the kidney of atherosclerotic rats. Biomedicine & Aging Pathology. 2012;2(4):212-5.

Eldaim MA, Tousson E, El Sayed IE, El AE, Elsharkawy HN. Grape seeds proanthocyanidin extract ameliorates Ehrlich solid tumor induced renal tissue and DNA damage in mice. Biomedicine & Pharmacotherapy. 2019;115:108908.

El Atrash A, Tousson E, Gad A, Allam S. Hematological and biochemical changes caused by antidepressants amitriptyline induced cardiac toxicity in male rats. Asian Journal of Cardiology Research. 2019;23:1-6.

Abouzeinab NS. Cytoprotective effect and antioxidant properties of silymarin on cisplatin induced hepatotoxicity in rats: A biochemical and histochemical study. Intern J Cancer Res. 2013;9(1): 9-23.

Nasr AY. Morphological, biochemical, histological, and ultrastructural protective effects of misoprostol on cisplatin induced-hepatotoxicity in adult male rats. Saudi Medical Journal. 2013;34(12):1237-1247.

Abdel-Wahhab MA, El-Denshary ES, El-Nekeety AA, Hassan NS, Abu-Salem FM, Sarhan NA, Rihn BH. Impact of soy isoflavones on aflatoxin-induced oxidative stress and hepatotoxicity in rats. General Health and Medical Sciences. 2014;1(2): 9-14.

Juma FD. Effect of liver failure on the pharmacokinetics of cyclophosphamide. Europ J Clinical Pharmacol. 1984;26(5): 591-593.

McDonald GB, Slattery JT, Bouvier ME, Ren S, Batchelder AL, Kalhorn TF, Schoch HG, Anasetti C, Gooley T. Cyclophosphamide metabolism, liver toxicity, and mortality following hematopoietic stem cell transplantation. Blood. 2003;101(5):2043-2048.

Moustafa AH, Ali EM, Moselhey SS, Tousson E, El-Said KS. Effect of coriander on thioacetamide-induced hepatotoxicity in rats. Toxicology and Industrial Health. 2014;30(7):621-9.

Salama AF, Tousson E, Ibrahim W, Hussein WM. Biochemical and histopathological studies of the PTU-induced hypothyroid rat kidney with reference to the ameliorating role of folic acid. Toxicology and Industrial Health. 2013;29(7):600-8.

Barakat LA, Tousson E, Ibrahim W, El-Hakeem AA. Role of propolis in improving hepatic and renal damage in boldenone undecylenate in male rats. American Journal of Biological Chemistry. 2015 29;3(1):8.

Alm-Eldeen A, Tousson E. Deterioration of glomerular endothelial surface layer and the alteration in the renal function after a growth promoter boldenone injection in rabbits. Human & Experimental Toxicol. 2012;31(5):465-72.

Denker B, Robles-Osorio ML, Sabath E. Recent advances in diagnosis and treatment of acute kidney injury in patients with cancer. Eur J Intern Med. 2011;22: 348–54.

Salahudeen AK, Bonventre JV. Onconephrology: The latest frontier in the war against kidney disease. J Am Soc Nephrol. 2013;24:26–30.

Cetiner M, Sener G, Sehirli AO, Eksioglu-Demiralp E, Ercan F, Sirvanci S, Gedik N, Akpulat S, Tecimer T, Yegen BC. Taurine protects against methotrexate-induced toxicity and inhibits leucocyte death. Toxicol. Appl. Pharmacol. 2005;209(1): 39-50.

Beyer J, Rick O, Weinknecht S, Kingreen D, Lenz K, Siegert W. Nephrotoxicity after high-dose carboplatin, etoposide and ifosfamide in germ-cell tumors: incidence and implications for hematologic recovery and clinical outcome. Bone Marrow Transplantation. 1997;20(10): 813.

Al-Ameri AS. Prevention of Etoposide induced kidney toxicity, electrolytes, injury and KI67 alternations in male rats treated with star anise. Journal of Bioscience and Applied Research. 2017;3(2-1):36-41.

Kleber M, Cybulla M, Bauchmüller K, Ihorst G, Koch B, Engelhardt M. Monitoring of renal function in cancer patients: An ongoing challenge for clinical practice. Ann Oncol. 2007;18:950–8.

Mizumoto K, Rothman RJ, Farber JL. Programmed cell death (apoptosis) of mouse fibroblasts is induced by the topoisomerase II inhibitor etoposide. Molecular Pharmacol. 1994;46(5):890-5.

Hande KR. Etoposide: Four decades of development of a topoisomerase II inhibitor. European Journal of Cancer. 1998;34(10):1514-21.

Burden DA, Osheroff N. Mechanism of action of eukaryotic topoisomerase II and drugs targeted to the enzyme. Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression. 1998;1400(1-3):139-54.