The Protective Effect of 9-Diaminoacridine against Ehrlich Ascites Carcinoma (EAC) Induced Spleen Injury in Female Mice
Asian Oncology Research Journal,
Background and Objective: The study aims to evaluate the protective activity of 9-Diaminoacridine (N1-(acridin-9-yl) propane-1, 3-diamine hydrochloride; 9-DAAD) against Ehrlich Ascites Carcinoma (EAC) bearing mice.
Materials and Methods: A total forty mice were randomly divided into four groups (1st group, control mice were injected with 0.1% DMSO 15 ml/ Kg bw subcutaneously; 2nd group, mice were administered with 9-DAAD (30 mmol/ kg bw every 3 day) subcutaneously for 2 weeks; 3rd group, mice were injected interaperitonealy with 2.5×106 EAC cells/mouse; 4th group, were injected with EAC as the 3rd group then administered with 9-DAAD for another 2 weeks).
Results: The results showed that; EAC exhibit a significant reduction in RBCs, Hb, HCT, MCV, MCH, MCHC levels. Moreover, EAC exhibit a significant elevation in WBCs and PLT levels when compared to the control group.
Many histopathological alterations were observed within the splenic tissue of the EAC group as cellular degeneration of red and white pulps, several necrotic cells, vacuolar degeneration, and notable amyloid deposition. In addition, there is a significant increase in the activity of caspase-3 and vascular endothelial growth factor (VEGF) expressions. On the other hand; treatment of EAC mice with 9-DAAD regularized serum levels of the above-mentioned parameters and also restore the splenic tissue normal histological architecture.
Conclusion: The results indicated that the 9-DAAD possesses a protective activity against EAC induced changes in blood, biochemical parameters and splenic injury. Further studies are warranted to explore its mode of action and safety for medicinal use in cancer therapy.
- 9-Diaminoacridine (9-DAAD)
- ehrlich ascites carcinoma (EAC)
- tumor markers
- vascular endothelial growth factor (VEGF).
How to Cite
Nataru S, Pulicherla Y, Gaddala B. A review on medicinal plants as a potential source for cancer. International Journal of Pharmaceutical Sciences Review and Research. 2014;26(1):235-248.
Ozaslan M, et al. Ehrlich ascites carcinoma. African Journal of Biotechnology. 2011;10(13):2375-2378.
Mutar TF, et al. Ehrlich ascites carcinoma bearing mice as model of human hepatocellular carcinoma. Asian Journal of Research and Reports in Hepatology. 2019;1-9.
Mutar TF, et al. Ameliorative effects of vitamin B17 on the kidney against Ehrlich ascites carcinoma induced renal toxicity in mice. Environmental Toxicology. 2020; 35(4):528-537.
Jemal A, et al. Global cancer statistics. CA: a cancer journal for clinicians. 2011; 61(2):69-90.
El-Masry TA, et al. The therapeutic and antineoplastic effects of vitamin B17 against the growth of solid-form Ehrlich tumours and the associated changes in oxidative stress, DNA damage, apoptosis and proliferation in mice. Pak. J. Pharm. Sci. 2019;32(6):2801-10.
El-Masry T, et al. Potential therapy of vitamin B17 against Ehrlich solid tumor induced changes in Interferon gamma, Nuclear factor kappa B, DNA fragmentation, Bcl2, survivin, VEGF and TNF-α Expressions in mice. Pak. J. Pharm. Sci. 2020;33(1):393-401.
Abd Eldaim MA, et al. Grape seeds proanthocyanidin extract ameliorates Ehrlich solid tumor induced renal tissue and DNA damage in mice. Biomedicine & Pharmacotherapy. 2019;115:108908.
Aldubayan MA, et al. Antineoplastic activity and curative role of avenanthramides against the growth of ehrlich solid tumors in mice. Oxidative medicine and cellular longevity; 2019.
Tousson E, et al. Hepatic ameliorative role of vitamin B17 against Ehrlich ascites carcinoma–induced liver toxicity. Environmental Science and Pollution Research. 2020;1-11.
Nadaraj V, Selvi ST, Mohan S. Microwave-induced synthesis and anti-microbial activities of 7, 10, 11, 12-tetrahydrobenzo [c] acridin-8 (9H)-one derivatives. European journal of medicinal chemistry. 2009;44(3):976-980.
Kalirajan R, et al. Synthesis of some novel pyrazole substituted 9 anilinoacridine derivatives and evaluation for their antioxidant and cytotoxic activities. Journal of Heterocyclic Chemistry. 2012;49(4):748-754.
Bacherikov VA, et al. Synthesis and antitumor activity of 5-(9-acridinylamino) anisidine derivatives. Bioorganic & medicinal chemistry. 2005;13(23):6513-6520.
Gamage SA, et al. Synthesis and in vitro evaluation of 9-anilino-3, 6-diaminoacridines active against a multidrug-resistant strain of the malaria parasite Plasmodium falciparum. Journal of Medicinal Chemistry. 1994;37(10):1486-1494.
Chen YL, et al. Synthesis and antiinflammatory evaluation of 9-anilinoacridine and 9-phenoxyacridine derivatives. Journal of medicinal chemistry. 2002;45(21):4689-4694.
Sondhi S, et al. Synthesis of sulpha drug acridine derivatives and their evaluation for anti-inflammatory, analgesic and anticancer activity; 2002.
Gamage SA, et al. Structure− activity relationships for the antileishmanial and antitrypanosomal activities of 1 ‘-substituted 9-anilinoacridines. Journal of Medicinal Chemistry. 1997;40(16):2634-2642.
Llama EF, et al. Synthesis and antinociceptive activity of 9-phenyl-oxy or 9-acyl-oxy derivatives of xanthene, thioxanthene and acridine. European Journal of Medicinal Chemistry. 1989;24(4):391-396.
Recanatini M, et al. SAR of 9-amino-1, 2, 3, 4-tetrahydroacridine-based acetylcholinesterase inhibitors: synthesis, enzyme inhibitory activity, QSAR, and structure-based CoMFA of tacrine analogues. Journal of medicinal chemistry. 2000;43(10):2007-2018.
Goodell JR, et al. Synthesis and evaluation of acridine-and acridone-based anti-herpes agents with topoisomerase activity. Bioorganic & medicinal chemistry. 2006;14(16):5467-5480.
da Rocha Pitta MG, et al. Synthesis and In vitro anticancer activity of novel thiazacridine derivatives. Medicinal Chemistry Research. 2013;22(5):2421-2429.
Ghosh R, Bhowmik S, Guha D. 9-Phenyl acridine exhibits antitumour activity by inducing apoptosis in A375 cells. Molecular and cellular biochemistry. 2012;361(1-2):55-66.
Abd Eldaim MA, Tousson E, El Sayed IE, Abd Elmaksoud AZ, Ahmed AA. Ameliorative effects of 9-diaminoacridine derivative against Ehrlich ascites carcinoma–induced hepatorenal injury in mice. Environmental Science and Pollution Research. 2021 Jan 7:1-6.
Fujimoto K. Principles of measurement in hematology analyzers manufactured by Sysmex Corporation. Sysmex Journal International. 1999;9(1; SEAS SUM):31-44.
El-Moghazy M, et al. 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):371-377.
Abd Eldaim MA, et al. Ameliorative effects of saussurea lappa root aqueous extract against Ethephon induced reproductive toxicity in male rats. Environmental Toxicology. 2019;34(2):150-159.
Jang ES, et al. Diagnostic performance of alpha-fetoprotein, protein induced by vitamin K absence, osteopontin, Dickkopf-1 and its combinations for hepatocellular carcinoma. PloS One. 2016;11(3): 0151069.
Tousson E. Histopathological alterations after a growth promoter boldenone injection in rabbits. Toxicology and Industrial Health. 2016;32(2):299-305.
Cook HC, Stirling R. Manual of histological techniques and their diagnostic application. Churchill Livingstone;1994.
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.
Sternberger L. The unlabelled antibody peroxidase-antiperoxidase (PAP) method. Immunohistochemistry; 1979.
Hassan AI, Abdel-Gawad EI. Effect of Zizyphus leaves extract on mice suffering from ehrlich ascites carcinoma. Nat. Sci. 2010;8(11):234-244.
Altun S, Ozalpan A. Interactive regeneration of liver and growth of Ehrlich ascites tumor in mice. Biologia-Bratislava. 2004;59(3):375-382.
Rajeshwar Y, Gupta M, Mazumder UK. Antitumor activity and in vivo antioxidant status of Mucuna pruriens (Fabaceae) seeds against Ehrlich ascites carcinoma in Swiss albino mice. Iranian Journal of pharmacology and Therapeutics. 2005; 4(1):46-0.
Shimizu M, et al. Expression of cytosolic phospholipase A2α in murine C12 cells, a variant of L929 cells, induces arachidonic acid release in response to phorbol myristate acetate and Ca2+ ionophores, but not to tumor necrosis factor-α. Journal of Pharmacological Sciences. 2004; 0411110008-0411110008.
Badr M, et al. Anti-tumour effects of Egyptian propolis on Ehrlich ascites carcinoma. Vet Italy. 2011;47(3): 341-350.
Pandya NB, et al. Antitumor and antioxidant status of Terminalia catappa against Ehrlich ascites carcinoma in Swiss albino mice. Indian Journal of Pharmacology. 2013;45(5):464.
Shivhare SC, et al. Antioxidant and anticancer evaluation of Scindapsus officinalis (Roxb.) Schott Fruits. Ayu. 2011;32(3):388.
Hashem M, Mohamed H, Magda S. Clinicopathological, pathological and biophysical studies on the effect of electromagnetic field on the Ehrlich tumor cells implanted in mice. Egypt J Comp Clin Pathol. 2004;17(2):117-147.
Gupta M, et al. Antitumor activity and antioxidant status of Caesalpinia bonducella against Ehrlich ascites carcinoma in Swiss albino mice. Journal of Pharmacological Sciences. 2004;94(2): 177-184.
Badr OM, Sakr S, Abd-Eltawab H. Ameliorative effect of ginger extract against pathological alterations induced in mice bearing solid tumors. Journal of Bioscience and Applied Research. 2016; 2(3): 185-196.
El-Masry TA, Al-Shaalan NH, Tousson E, Buabeid M, Alyousef AM. The therapeutic and antineoplastic effects of vitamin B17 against the growth of solid-form Ehrlich tumours and the associated changes in oxidative stress, DNA damage, apoptosis and proliferation in mice. Pak. J. Pharm. Sci. 2019;32(6):2801-10.
El-Wahab A, Samia M, Fouda FM. Histological and histochemical study on the effect of Ehrlich ascites carcinoma on the liver and kidney of mice and the possible protective role of tetrodotoxin. Egyptian Journal of Biology. 2009;11.
Salem FS, Badr M, Neamat-Allah A. Biochemical and pathological studies on the effects of levamisole and chlorambucil on Ehrlich ascites carcinoma-bearing mice. Vet Ital. 2011;47(1):89-95.
Perrone RD, Madias NE, Levey AS. Serum creatinine as an index of renal function: New insights into old concepts. Clinical chemistry. 1992;38(10):1933- 1953.
Geraci J, et al. Kidney and lung injury in irradiated rats protected from acute death by partial-body shielding. Radiation Research. 1990;122(1):95-100.
Lazarevich N. Molecular mechanisms of alpha-fetoprotein gene expression. Biochemistry C/C of Biokhimiia. 2000; 65(1):117-133.
Medhat D, et al. Effect of au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations. Biomedicine & Pharmacotherapy. 2017;91: 1006-1016.
Zhu Z, Witte L. Inhibition of tumor growth and metastasis by targeting tumor-associated angiogenesis with antagonists to the receptors of vascular endothelial growth factor. Investigational new drugs. 1999;17(3):195-212.
Veikkola T, et al. Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer research. 2000;60(2):203-212.
Grunstein J, et al. Tumor-derived expression of vascular endothelial growth factor is a critical factor in tumor expansion and vascular function. Cancer Research. 1999;59(7): 1592-1598.
Abstract View: 231 times
PDF Download: 99 times