Moringa extract reduces DNA fragmentation and ameliorates Tamoxifen®-induced hepatotoxicity in rats
DOI:
https://doi.org/10.56511/JIPBS.2019.v6.i04.pp11-22Abstract
Breast cancer is the most common cancer among women, and it causes the most deaths after lung cancer. Tamoxifen® (TMX) is a known chemopreventive agent that widely used for treatment of breast cancer; however it presents several side effects. The objective of this study was to elucidate the efficacy of Moringa aqueous extract (MAE) in reduction of DNA-fragmentation and amelioration of the hepato-pathophysiological complications sided by TMX. Adult male Wistar rats (150-170g) were randomly divided into four groups (10 animals each group) as follows: group (1): Rats administrated with saline and served as control, group (2): Rats orally administrated with MAE (300 mg/Kg b.wt./day), group (3) Rats intoxicated with TMX (3mg/Kg/3days), and group (4); Rats daily treated with MAE in combination with TMX. After consecutive six weeks, the results revealed that the administration of MAE markedly restored the pathophysiological deteriorations resulted from TMX-intoxication; This was evidenced by the marked reduction in serum ALAT, ASAT, GGT, ALP and bilirubin as well as the improvement in the serum level of total protein, albumin, creatinine, urea, Na and K. Moreover, the microscopic examinations showed marked regeneration of the hepatocytes. These findings were in line with the reduction of DNA-fragmentation and could be mechanized through the antioxidant and anti-inflammatory battery of moringa constituents. In conclusion, MAE could play a beneficial role for prevention of TMX-induced pathophysiological distortions. So, it may be worthy to consider the beneficial use of moringa extract as a supplement with the TMX therapy.
Keywords:
Hepatotoxicity, Tamoxifen®, Moringa oleifera, DNA, RatDownloads
References
McGuire A., Brown J.A., Malone C., McLaughlin R., Kerin M. J. Effects of age on the detection and management of breast cancer. Cancers. J. 2015; 7: 908 – 29.
Cuzick J., Arbyn M., Sankaranarayanan R., Tsu V., Ronco G., Mayrand M. H., Meijer C. J. Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine 2008; 26: 29-41.
Shibutani S., Suzuki N., Laxmi Y.R., Schild L.J., Divi L.J., Divi R.L., Grollman A.P., Poirier M.C. Identification of tamoxifen-DNA adducts in monkeys treated with tamoxifen. Cancer Res 2003; 63:4402 – 4406.
Gaikwad N.W., Bodell W.J. Peroxidase mediated dealkylation of Tamoxifen detected by ESIMS and activation to form of DNA adducts. Free Radic. Biol. Med. 2012; 15: 52(2): 340 – 347.
Constantine G.D., Kessler G., Graham S., Goldstein, S.R. Increased Incidence of Endometrial Cancer Following the Women’s Health Initiative: An Assessment of Risk Factors. Journal of Women’ s Health 2019; 28: 2.
Huang F., Yin J., Li K., Li Y., Qi H., Fang L., Yuan C., Liu W., Wang M., Li X. GPR30 decreases with vascular aging and promotes vascular smooth muscle cells maintaining differentiated phenotype and suppressing migration via activatio n of ERK1/2 . Onco Targets Ther . 2016; 9 :3415 – 3422.
Rockwood J.L., Anderson B.G., Casamatta D.A., Potential uses of Moringa oleifera and an examination of antibiotic efficacy conferred by Moringa oleifera seed and leaf extracts using crude extraction techniques available to underserved indigenous populations. Int J Phytothearpy Res. 2013; 3: 61 – 71.
Divi S.M., Bellamkona R., Dasireddy S.K. Evaluation of Antidiabetic and Antihyerlipedemic Potential of Aqueous Extract of Moringa Oleifera in Fructose Fed Insulin Resistant and STZ Induced Diabetic Wistar Rats. Asian J Pharm Clin Res. 2012; 5: 67-72.
Pfeffer C.M., Singh A.T.K. Apoptosis: A Target for Anticancer Therapy. Int. J. Mol. Sci. 2018; 19448.
Moussa S.A., Abdel-Wahhab K.G., Mannaa F.A. Moringa oleifera inhibited the toxicity induced by administration of Tamoxifen in rats: using ultraviolet-visible and fluorescence spectroscopy investigations. JIPBS 2018; 5 (1): 60-64.
Berkovich L., Gideon E. , Ilan R. , Adam R. , Akiva V. , Shahar L. Moringa Oleifera aqueous leaf extract down-regulates nuclear factor-kappaB and increases cytotoxic effect of chemotherapy in pancreatic cancer cells BMC Complement Altern Med . 2013; 13: 212.
Jayapraksha G.K., Jaganmohan R.L., Sakariah K.K. Antioxidant activity of flavidin in different in vitro model system. Bioorg Med Chem . 2004; 12 (19): 5141 - 5146.
Nogala-Kalucka M., Korczak J., Dratwia M., Lampart-szczapa E., Siger A., Buchowski M. Changes in antioxidant activity and free radical scavenging potential of rosemary extract and tocopherols in isolated rapeseed oil triacylglycerols during accelerated tests. Food chem. 2005; 93:227-235.
Ruiz-Larrea M.B., Leal A.M., Liza M., Lacort M., Groot H. Antioxidant effects of estradiol and 2-hydroxyestradiol on ironinduced lipid peroxidation of rat liver microsomes. Steroids. 1994; 59:383-8.
Perandones C.E., Illera V.A., Peckham D., Stunz L.L., Ashman R.F. Regulation of apoptosis in vitro in mature murine spleen T cells. J Immunol. 1993; 151(7): 3521-9.
Drury R.A.B., Wallington E.A. Preparation and fixation of tissues. In: Drury RAB, Wallington EA, editors. Carleton's Histological Technique. 5. Oxford: Oxford University Press 1980; 41 – 54.
Waller R.A. Duncan D. B. A Bayes rule for the symmetric multiple comparisons problems. Journal of the American Statistical Association. 1969; 64: 14841503.
Lorizio W., Wu A.H., Beattie M.S., Rugo H., Tchu S., Kerlikowske K., Ziv, E.. linical and biomarker predictors of side effects from tamoxifen.Breast Cancer Res. 2012;132:1107 – 1118.
Yang G., Nowsheen S., Aziz K., Georgakilas A.G. Toxicity and adverse effects of Tamoxifen and other anti-estrogen drugs. Pharmacol. Ther. J. 2013; 139: 392 – 404.
Hassanein N.M.A., Ali A.A. El-Khawaga A.M.E. Methylseleninic Acid and Grape Seed Extract Alleviate Tamoxifen Induce Hepatotoxicity in Rats. Toxicol. Environ. Health. Sci. Vol. 2018; 10(5): 278-287.
El-Kashef D.H., El-Sheakh A.R. Hepatoprotective effect of celecoxib against tamoxifen-induced liver injury via inhibiting ASK-1/JNK pathway in female rats Life Sciences 2019; 231 - 116573.
McClatchey K.D. Clinical laboratory medicine. Lippincott Williams & Wilkins. app. ISBN. 2011; 978: 683-30751.
Suddek G.M. Protective role of thymoquinone against liver damage induced by tamoxifen in female rats. Can. J. Physiol. Pharmacol. J. 2014; 92: 640-644.
Rahate K.P., Rajasekaran A. Hepatoprotection by active fractions from Desmostachya bipinnata stapf (L.) against tamoxifen-induced hepatotoxicity. Indian J Pharmacol. 2015; 47:311-5.
Nazarewicz, R.R. et al. Tamoxifen induces oxidative stress and mitochondrial apoptosis via stimulating mitochondrial nitric oxide synthase. Cancer Res. 2007; 67: 1282 – 1290.
Hon W.M., LeeK. H., KhooH. E. Nitric oxide in liver diseases: friend, foe, or just passerby Acad. Sci. 2002; 962: 275-295.
Charalambous C., Pitta C.A. Constantinou A.I. Equol enhances tamoxifen’s anti -tumor activity by induction of caspase-mediated apoptosis in MCF-7 breast cancer cells. BMC Cancer 2013; 13: 1471-2407.
Yeh W.L., Lin, H.Y., Wu, H.M. Chen, D.R. Combination treatment of tamoxifen with risperidone in breast cancer. PLoS ONE 9, doi: 10.1371/journal. pone.0098805 (2014).
Essawy A, Beeker H.M., Abdel-Wahhab K.G.,Sayad O.N., Saber S.R. Efficacy of Moringa oleifera Aqueous Extract in Inhibiting Tamoxifen ® - Induced Physiological Hepatic Deterioration in Male Albino Rats. Egypt. Acad. J. Biolog. Sci. 2017; 9(2): 2337.
Qasim A.H., Baraj A.H. Histological and Biochemical Study of Different Doses of Tamoxifen Drug on Liver of Albino Male Rat. Journal of Pharmacy and Biological Sciences Ver. VIII (Jul – Aug 2017); 12(4): 67-
Pari L., Karthikesan K. Protective role of caffeic acid against alcohol – Induced biochemical changes in rats. Fundam Clin Pharmacol. 2007; 21(4): 355-361.
Selvakumar D., Natarajan P. Hepatoprotective activity of Moringa oleifera Lam. leaves in carbon tetrachloride induced hepatotoxicity in albino rats.Pharmacogn. Mag. 2008; 4: 97-98.
Buraimoh A.A., Bako I.G. Ibrahim F.B. Hepatoprotective Effect of Ethanolic Leaves Extract of Moringa oleifera on the Histology of Paracetamol Induced Liver Damage in Wistar Rat. International Journal of Animal and Veterinary Advances 2011; 3: 10-13.
Islam R., Alam J. Evaluation of liver protective activity of Moringa oleifera bark extract in paracetamol induced hepatotoxicity in rats. 2019; 7.
Okumu M.O., Mbaria J.M., Kanja L.W., Gakuya D.W., Kiama S.G., Ochola F.O. Phytochemical profile and antioxidant capacity of leaves of Moringa oleifera (lam) extracted using different solvent systems. J. Pharmacogn. Phytochem. 2016; 5(4):302 – 8.
Li S., Hong M., Tan H.Y., Wang N., Feng Y. Insights into the role and interdependence of oxidative stress and inflammation in liver diseases. Oxid. Med. Cell Longev. 2016; doi: 10.1155/2016/4234061.
Järvinen L.S., PyrhönenS., Kairemo K.J., PaavonenT. The effect of antioestrogens on cytokine production in vitro. Scand. J. Immunol. 1996; 44: 15-20.
Miyamura M., Yokota J. Saibara T. Drug-induced Nonalcoholic Steatohepatitis. Journal of Pharmaceutical Society of Japan 2016; 136: 579-582.
Fromenty B., RobinM.A., Igoudjil A., Mansouri A. Pessayre, D. The ins and outs of mitochondrial dysfunction in NASH. Diabetes Metab. 2004; 30: 121-138.
Saini R.K., Manoj P., Shetty N.P., Srinivasan K., Giridhar P. Dietary iron supplements and Moringa oleifera leaves influence the liver hepcidin messenger RNA expression and biochemical indices of iron status in rats. Nutr. Res. 2014; 34:630-8.
Abdurrauf Y., Ahmet A., Atessahin O., Ali C. Mesut A.. Ellagic acid prevent Cisplatin 10 mg kg-1 platin-Induced oxidative stress in liver and heart tissue of rats. Basic. Clin. Pharmacol. Toxicol. 2007; 101:345-349.
Duan X, Wu G, Jiang Y. Evaluation of the antioxidant properties of litchi fruit phenolics in relation to pericarp browning prevention. Molecules. 2007; 12(4):759 – 71.
Published
How to Cite
Issue
Section
Copyright (c) 2019 Mahmoud Ashry, Heba Fawzi, Mohamed A. Mustafa, Fatma Adly Morsy, Sherif A.A Moussa, Khaled G. Abdel-Wahhab

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.


Journal of Innovations in Pharmaceutical and Biological Sciences is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Based on a work at