Contribution of garlic for improving the cytoprotective effect of mesna against cyclophosphamide toxicity in rats

Enas Abdelaziz Tahoun; Nermeen Borai El- Borai; Hanem Kamal Khalifa; Hanem El- Gendy

doi:10.30574/gscbps.2019.7.3.0089

Authors

Enas Abdelaziz Tahoun Department of Pathology, Faculty of Veterinary medicine, University of Sadat City, Egypt.
Nermeen Borai El- Borai Department of Forensic Medicine and Toxicology, Faculty of Veterinary medicine, University of Sadat City, Egypt.
Hanem Kamal Khalifa Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary medicine, University of Sadat City, Egypt.
Hanem El- Gendy Department of Pharmacology, Faculty of Veterinary medicine, University of Sadat City, Egypt.

DOI:

https://doi.org/10.30574/gscbps.2019.7.3.0089

Keywords:

Cyclophosphamide, Garlic, Mesna, Hematology, Histopathology

Abstract

Cyclophosphamide (CYP), an oxazophosphorine- alkylating agent, is a widely used drug for treatment of neoplastic and severe autoimmune diseases. Adverse effects of CYP restrict its therapeutic benefits. Mesna (MS), a thiol compound, is used as a protective agent against hemorrhagic cystitis induced by CYP. This study aimed to investigate the potential role of raw garlic homogenate (RGH) for improving the protective effect of mesna against CYP toxicity in rats. Thirty male albino rats were divided into five equal groups. Control group, CYP group (a single i.p. dose, 200 mg/kg b.wt.), CYP+MS group (a total dose of 120 mg/kg b.wt. in three equal doses, i.p.), CYP+RGH group (500 mg/kg b.wt., orally, once daily 5 days before and after CYP injection) and CYP+MS+RGH group. CYP induced hematological changes, including significant reduction of RBCs, Hb, PCV with thrombocytopenia and leukocytopenia. Also, significant increase in serum MDA content concomitantly with significant reduction in TAC was recorded. This was associated with histopathological alterations in the examined tissues. However, mesna and/or garlic improved the recorded hematological, biochemical and histopathological alterations induced by CYP with marked improvement using their combination. In conclusion, garlic supplementation in combination with mesna could be of a great value to introduce therapeutic strategies for patients undertaking cyclophosphamide therapy.

Metrics

Metrics Loading ...

References

Matz EL and Hsieh MH. (2017). Review of Advances in Uroprotective Agents for Cyclophosphamide- and Ifosfamide-induced Hemorrhagic Cystitis. Urology, 100, 10-16.

Morandi P, Ruffini PA, Benvenuto GM, Raimondi R and Fosser V. (2005). Cardiac toxicity of high-dose chemotherapy. Bone Marrow Transplant, 35, 323–334.

Uber WE, Self SE, Van Bakel AB and Pereira NL. (2007). Acute antibody mediated rejection following heart transplantation. Am J Transplant, 7(9), 2064-2074.

Perini P, Calabrese M, Rinaldi L and Gallo P. (2008). Cyclophosphamide-based combination therapies for autoimmunity. Neurological Science, 29, 233-234.

Suwa A, Hirakata M, Satoh S, Mimori T, Utsumik K and Inada S. (1999). Rheumatoid arthritis associated with methotrexate-induced pneumonitis: Improvement with cyclophosphamide therapy. Clinical Experimental Rheumatology, 17, 355-358.

Sharda SV, Gulati S, Tripathi G, Jafar T, Kumar A, Sharma RK and Agrawal S. (2008). glutathione-S-transferase polymorphisms influence response to intravenous cyclophosphamide therapy in idiopathic nephrotic syndrome? Pediatric Nephrology, 23, 2001–2006.

Hu RQ, Mehter H, Nadasdy T, Satoskar A, Spetie DN and Rovin BH. (2008). Severe hemorrhagic cystitis associated with prolonged oral cyclophosphamide therapy: case report and literature review. Rheumatology International, 28, 1161–4.

Viswanatha-Swamy, AH, Patel, UM, Koti, BC, Gadad, PC, Patel, NL and Thippeswamy, AH. (2013). Cardioprotective effect of Saraca indica against cyclophosphamide induced cardiotoxicity in rats: A biochemical, electrocardiographic and histopathological study. Indian Journal of Pharmacology, 45(1), 44–48.

Conklin DJ, Haberzettl P, Jagatheesan G, Baba S, Merchant ML, Prough RA, Williams JD, Prabhu, SD and Bhatnagar A. (2015). Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice. Toxicology and Applied Pharmacology, 285(2), 136–148.

Amien AI, Fahmy SR, Abd-Elgleel FM and Elaskalany SM. (2015). Renoprotective effect of Mangifera indica polysaccharides and silymarin against cyclophosphamide toxicity in rats. The Journal of Basic & Applied Zoology, 72, 154–162.

Khorwal G, Chauhan R and Nagar M. (2017). Effect of cyclophosphamide on liver in albino rats: A comparative dose dependent histomorphological study. International Journal of Biomedical and Advance Research, 8(03), 102-107.

Kyung YS, Park HY and Lee G. (2011). Preservation of uroplakins by 2-mercaptoethanesulfonate in cyclophosphamide-induced rat cystitis. Archives of Toxicology, 85, 51-57.

Triantafyllidis T, Taitzoglou I, Kesisoglou I, Lazaridis C and Botsios D. (2015). Treatment with Mesna and n‐3 polyunsaturated fatty acids ameliorates experimental ulcerative colitis in rats. International Journal of Experinmental Pathology, 96(6), 433–443.

Sak K. (2012). Chemotherapy and Dietary Phytochemical Agents. Chemotherapy Research and Practice, 2012, Article ID 282570, 11 pages.

Petrovic V, Nepal A, Olaisen C, Bachke S, Hira L, Søgaard CK, Røst LM, Misund K, Andreassen T, Melø TM, Bartsova Z, Bruheim P and Otterlei M (2018). Anti-Cancer Potential of Homemade Fresh Garlic Extract Is Related to Increased Endoplasmic Reticulum Stress. Nutrients, 10(4), 450.

El-Sheshtawy SM, El-Keredy MS and Eltalawy MF. (2016). Antioxidant Potential and Toxicity of Garlic (Allium sativum). Egyptian Journal of Chemistry and Environmental Health, 2 (2), 56-65.

Josling PA. (2005). The heart of garlic Nature's aid to healing the human body, HEC Publishing, Chicago Illinois, 20.

Capasso A. (2013). Antioxidant action and therapeutic efficacy of allium sativum L. Molecules, 18(1), 690–700.

Douaouya L. and Bouzerna N. (2016). Effect of garlic (allium sativum l) on biochemical parameters and histopathology of pancreas of alloxan-induced diabetic rats. International Journal of Pharmacy and Pharmaceutical Sciences, 8 (6), 202-206.

Şengül E, Gelen V, Gedikli S, Özkanlar S, Cur S and Çınar A. (2017). The protective effect of quercetin on cyclophosphamide-Induced lung toxicity in rats. Biomedicine & Pharmacotherapy, 92, 303-307.

Kanat O, Kurt E, Yalcinkaya U, Evrensel T and Manavoglu O. (2006). Comparison of roprotective efficacy of mesna and amifostine in Cyclophosphamide- induced hemorrhagic cystitis in rats. Indian Journal of Cancer, 43(1), 12-15.

Weiss DJ and Wardrop KJ. (2010). Schalm’s Veterinary Hemetology. New York, Blackwell, 6th ed.

Ohkawa H, Ohishi W and Yagi K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95, 351-358.

Koracevic D, Koracevic G, Djordjevic V, Andrejevic S and Cosic V. (2001). Method for the measurement of antioxidant activity in human fluids. J. Clin. Pathol.54, 361-356.

Bancroft JD and Gamble M. (2008). Theory and Practice of histological techniques". 6th Edition. Churchill, Livingstone, New York, London. 440-450.

Eolayinka ET, Ore A, Ola OS and Adeyemo OA. (2015). Ameliorative Effect of Gallic Acid on Cyclophosphamide-Induced Oxidative Injury and Hepatic Dysfunction in Rats. Medical Science (Basel), 3(3), 78–92.

Cengiz M. (2018). Hematoprotective effect of boron on cyclophosphamide toxicity in rats. Cellular and Molecular Biology, 64(5), 62-65.

Elshater AA, Haridy MAM, Salmana MMA, Fayyada AS and Hammad S. (2018). Fullerene C60 nanoparticles ameliorated cyclophosphamide-induced acute hepatotoxicity in rats. Biomedicine & Pharmacotherapy, 97, 53–59.

Vadhan-Raj S. (2009). Management of chemotherapy-induced thrombocytopenia: current status of thrombopoietic agents. Seminars in Hematology, 46(1-2), S26-32.

Gunes S, Ayhanci A, Sahinturk V, Altay D and Uyar R. (2017). Carvacrol attenuates cyclophosphamide-induced oxidative stress in rat kidney. Canadian Journal of Physiology and Pharmacology, 95 (7), 844-849.

Hermenean A, Ardelean A and crăciun C. (2008). Spleen Structural Damages and Tissular Biochemical Parameters Disturbances at Wistar Rats after Chemotherapy Administration. Life Sciences Series, 18, 255-258.

Tasdemir S, Tasdemir C, Vardi N, Ates B, Taslidere E, Karaaslan MC, Sapmaz HI, Sagir M, Kurt A and Baser CA. (2013). Effects of Ozone therapy on Cyclophosphamide-induced Urinary Bladder Toxicity in Rats. Clinical and Investigative Medicine, 36 (1), E9-E17.

Ahmed LA, EL-Maraghy SA, and Rizk SM. (2015). Role of the KATP channel in the protective effect of nicorandil on cyclophosphamide-induced lung and testicular toxicity in rats.

Omole JG, Ayoka OA, Alabi QK, Adefisayo MA, Asafa MA, Olubunmi BO and Fadeyi BA. (2018). Protective Effect of Kolaviron on Cyclophosphamide-Induced Cardiac Toxicity in Rats. Journal of Evidence-Based Integrative Medicine, 23, 1-11.

Bokolo B and Adikwu E. (2018). Protective assessment of cimetidine against cyclophosphamide-induced kidney injury. Asian Journal of Medical Sciences, 9 (6), 25-30.

Motawi TM, Sadik NA and Refaat A. (2010). Cytoprotective effects of DL alpha- lipoic acid or squalene on cyclophosphamide-induced oxidative injury: an experimental study on rat myocardium, testicles and urinary bladder. Food and Chemical Toxicology, 48(8-9), 2326-2336.

Haque R, Bin-Hafeez B, Parvez S, Pandey S, Sayeed I, Ali M and Raisuddin S. (2003). Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamide induced biochemical toxicity. Human and Experimental Toxicology, 22, 473-80.

Honjo T, Suou T and Hirayama C. (1988). Hepatotoxicity of cyclophosphamide in man: pharmacokinetic analysis. Research Communication in Chemical Pathology and Pharmacology, 61(2), 149-165.

Wu X, Guo R, Chen P, Wang Q and Cunningham PN. (2009). TNF induces caspase-dependent inflammation in renal endothelial cells through a Rho and myosin light chain kinase dependent mechanism. American Journal of Physiology and Renal Physiology, 297, 316-326.

Ozcan A, Korkmaz A, Oter S and Coskun O. (2005). Contribution of flavonoid antioxidants to the preventive effect of mesna in cyclophosphamide- induced cystitis in rats. Archives Toxicology, 79(8), 461-5.

Ahmed RA. (2018). Hepatoprotective and antiapoptotic role of aged black garlic against hepatotoxicity induced by cyclophosphamide. The Journal of Basic and Applied Zoology, 79 (8), 1-8.

El-Sebaey AM, Abdelhamid FM and Abdalla OA. (2019). Protective effects of garlic extract against hematological alterations, immunosuppression, hepatic oxidative stress, and renal damage induced by cyclophosphamide in rats. Environmental Science and Pollution Resarch.

Shepherd JD, Pringle LE, Barnett MJ, Klingemann HG, Reece DE and Phillips GL. (1991). Mesna versus hyperhydration for the prevention of cyclophosphamide-induced hemorrhagic cystitis in bone marrow transplantation. Journal of Clinical Oncology, 9(11), 2016-2020.

Mashiach E, Sela S, Weinstein T, Cohen HI, Shasha SM and Kristal B. (2001). Mesna: A novel renoprotective antioxidant in ischaemic acute renal failure. Nephrology Dialysis Transplantation, 16, 542-551.

Şener G, Sehirli Ö, Cetinel S, YeSen BG, Gedik N and Dülger A. (2005). Protective effects of MESNA (2-mercaptoethane sulphonate) against acetaminophen-induced hepatorenal oxidative damage in mice. Journal of Applied Toxicology, 25, 20–29.

Şener G, Kabasakal L, Sehirli O, Ercan F and Gedik N. (2006). 2-Mercaptoethane sulfonate (MESNA) protects against biliary obstruction-induced oxidative damage in rats. Hepatology Research, 35(2), 140-6.

Bongiorno PB, Fratellone PM and LoGiudice P. (2008). Potential health benefits of garlic (Allium sativum): a narrative review. Journal of Complementary Integrative Medicine, 5(1), 1–26.

Alkreathy H, Zoheir AD, Nessar A, Mark S, Soad SA and Osman AM. (2010). Aged garlic extract protects against doxorubicin-induced cardiotoxicity in rats. Food and Chemical Toxicology, 48, 951–956.

Lawal AO and Ellis EM. (2011).The chemopreventive effect of aged garlic extract against cadmium-induced toxicity. Environmental Toxicology and Pharmacology, 32, 266–274.

Abd El-Halim SS and Mohamed MM. (2012). Garlic powder attenuates acrylamide-induced oxidative damage in multiple organs in Rat. Journal of Applied Sciences Research, 8(1), 168–173.

Nasr AY and Saleh HAM. (2014). Aged garlic extract protects against oxidative stress and renal changes in cisplatin-treated adult male rats. Cancer Cell International, 28(14), 92.

Colin-Gonzalez AL, Santana RA, Silva-Islas CA, Chanez-Cardenas ME, Santamarıa A and Maldonado PD. (2012).The antioxidant mechanisms underlying the aged garlic extract- and S-allylcysteine-induced protection. Oxidative Medicine and Cellular Longevity, 907, 162-78.