Effect of Pomegranate Seed Oil against Hepatotoxicity- Induced by Sodium Fluoride in Adult Female Rats (Part II). براء نجم العقيلي وإيلاف حسين علي

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Baraa Najim Al-Okaily
Ellaf Hussian Ali


This experiment was designed to evaluate the hepatoprotective effects of pomegranate seed oil against toxicity- induced by sodium fluoride and in normal rats. Twenty  adult female Wistar rats were divided into four equal group and treated daily for 40 days as follows: Group C administered  tap water and served as control , group T1 : received sodium fluoride 120ppm in drinking tap water, group T2: received both sodium fluoride 120ppm in drinking water and  administered orally pometone (pomegranate seed oil) 30mg/kg B.W. and group T3 : administered pomegranate seed oil as in group T2 orally. Fasting blood samples were collected at 0, 20 and 40 days to estimation of some biochemical parameters and oxidative stress biomarkers . In addition, sections from liver were taken at the end of the experiment for histopathological study. The results revealed that SF (group T1) caused a significant increase in serum aminotransferases (serum alanine aminotransferase and aspartate aminotransferase) activities, total cholesterol ,total bilirubin and peroxynitrite radical concentrations, while GSH concentration was a significantly decrease.  PSO caused an alleviation to the hepatic dysfunction induced by sodium fluoride (group T2) manifested through significant elevation of GSH concentration, in addition, a significant reduction in serum transaminases activity, total cholesterol, peroxynitrite radical and total bilirubin concentrations. In contrast, administration of pomegranate seed oil (group T3) showed no alterations in most of these parameters. Furthermore  histopathological examination of liver tissues of  group T1 manifested aggregation of mononucleated cells, proliferation of hepatocyte, cytoplasmic fat droplet and granulomatous lesion consists of aggregation of macrophage and lymphocyte. All these alteration in liver histology were modified by treatment of rats with pomegranate seed oil (group T2) and no pathological lesion was reported in group T3. On conclusion, this study documented the beneficial effect of pomegranate seed oil against the deleterious effects of SF on liver functions of adult female rats.


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Al-Okaily, B. N., & Ali , E. H. (2019). Effect of Pomegranate Seed Oil against Hepatotoxicity- Induced by Sodium Fluoride in Adult Female Rats (Part II).: براء نجم العقيلي وإيلاف حسين علي. The Iraqi Journal of Veterinary Medicine, 43(1), 102–112. https://doi.org/10.30539/iraqijvm.v43i1.480


Environmental Protection Agency (EPA). (2007). Reregistration eligibility decision sodium fluoride. Washington, D.C. 20460.

Mueller, W.H. (2001). Fluoride compounds, inorganic, sodium. Encyclopedia of chemical Technology. John Wiley and Sons, inc.

Community Water Fluoridation: " Frequently Asked Questions” .(2013).Centers for Disease Control and Prevention, 6.

Villa, A.; Cabezas, L.; Anabalon, M. and Garza, E. (2004).The fractional urinary fluoride excretion of adolescents and adul ts

under customary fluoride intake conditions, in a community with 0.6-mg F/L in its drinking water.Com. Dent. Health, 21: 11–18.

Featherstone, J.D.B. (2000). The science and practice of caries prevention. J Am Dent Assoc., 131:887–899.

Ten Cate,F.M.(2013). Contemporary perspective on the use of fluoride products in caries prevention.

British Dental Journal 214, 161 – 167.

Waugh, D.T; Potter, W.; Limeback, H. and Godfrey, M. (2016).Risk Assessment of fluoride intake from tea in the republic of

Ireland and its implications for public health and water fluoridation. Int. J. Environ. Res. Public Health. 13,259;

doi: 10.3390/ijerph 1303259.

Susheela, A.K.; Bhatnagar, M.; Vig, K. and Mondal, N.K. (2005). Excess fluoride ingestion and thyroid hormone derangements

in children living in Delhi, India. Fluoride, 38: 98-108.

Roy, S. and Dass , G. (2013). Fluoride Contamination in Drinking Water – A Review Resources and Environ ment., 3(3): 53-58.

Ulemale, A.H.; Kulkarni, G.B.; Yadav, S.R.; Samant, S.J.; Komatwar and Khanvilkar, A.V. (2010). Fluorosis in Cattle. Veterinary

World. 3(11):526-527.

Hordyjewska, A. and Pasternak, K., (2004). Influence of fluoride on organism of human. J. Elementol. 9 (4):883–987.

Yadavi, S.S.; Kumar, R.; Khare, P. and Tripathi, M.(2015). Oxidative Stress Biomarkers in the Freshwater Fish,

Heteropneustes fossilis (Bloch) Exposed to Sodium Fluoride: Antioxidant Defense and Role of Ascorbic Acid Toxicol Int.,

(1): 71–76. doi:10.4103/0971-6580.172261

Shanmugam, K.R. and Srinivas, Reddy A.(2015). Protective effect of vitamin C in sodium fluoride (NAF) induced toxicity in

fishes: a study with reference to lipid metabolic profiles and liver markers. Indian Journal of Fundamental and Applied Life

Sciences. 5 (4):1-5.

Abdel-Wahab, W.M.(2013). Protective effect of thymoquinone on sodium fluoride-induced hepatotoxicity and oxidative stress in rats. The Journal of Basic & Applied Zoology, 66: 263–270.

Jha, A.; SHAH, K. and VERMA, R. (2012).Effects of sodium fluoride on DNA, RNA and protein contents in liver of mice

and its amelioration by Camellia Sinensis. Acta Poloniae Pharmaceutica-Drug Research, 69(3): 551-555.

Ali, E.H. and Al-Okaily,B.N. (2016). The protective role of pomegranate seed oil (Pometone) on serum protein in sodium

fluoride treated female rats.(Part I). IJVM. 39 (2):61-68.

Jing, P.; Ye, T.; Shi, H.; Sheng, Y.; Slavin, M.; Gao, B.; Liu, L. and Yu, l.(2012).Antioxidant properties and phytochemical composition of China-grown pomegranate seeds. Food Chemistry.132, (3):1457–1464.

Dipak,G.; Axay, P.; Chakraborty Manodeep, CM. and Kamath J.V.(2012).Phytochemical and pharmacological profile of Punica

granatum : an overview. IRJP,3 (2):65.

Fadavi, A.;Barzegar, M.; Azizi, M.H. and Bayat, M. (2005). Note.Physico -chemical composition of ten pomegranate cultivars

(Punica granatum L.) grown in Iran Food Science and Technology International, 11: 113–119.

Sumner, M.D.; Elliott-Eller, M.; Weidner, G.; Daubenmier, J.J.; Chew, M.H.; Marlin, R.; Raisin, C.J. and Ornish, D., (2005).

Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease. The American

Journal of Cardiology, 96:810-814.

Singh, M.; Arseneault, M.; Sanderson, T.; Murthy, V. and Ramassamy, C. (2008). Challenges for research on polyphenols from

foods in alzheimer’s disease: bioavailability, metabolism, and cellular and molecular mechanisms. Journal of Agricultural and

Food Chemistry, 56, 4855-4873.

Bhowmik, D.; Gopinath, H.; Kumar, P.; Duraivel, S.; Aravind, G. and Kumar, K.P.S. (2013). Medicinal uses of Punica granatum

and its health benefits. J Pharmacognosy and Phytochemistry. 1 (5): 28-35.

Boroushaki, M.T.; Mollazadeh , H. and Amir Reza Afshari, A.R. (2016). Pomegranate seed oil: A comprehensive review on its

therapeutic effects. IJPSR, 7(2): 1000-13.

Miguel, M.G.; Neves, M.A. and Antunes, M.D. (2010). Pomegranate (Punica granatum): A medicinal plant with myriad

biological properties – A short review. J of Medicinal Plants Research, 4: 2836-2847.

Gram DY, Atasever A, Eren M.(2018). Effect of pomegranate (Punica granatum) seed oil on carbon tetrachloride-induced

acute and chronic hepatotoxicity in rats. Phcog Res ., 16 (10) :124-9.

Medjakovic, S. and Jungbauer, A. (2013). Pomegranate: a fruit that ameliorates metabolic syndrome. Food Funct, 4: 19-39.

Abdullah,L.N. and AL-Okaily,B.N. (2014).Cardioprotective role of Pometone(pomegranate seed oil) on electrocardiography in methionine over load rabbits.( Part-I).Internat. Interdisciplinary J.6: 21-36.

Reitman, S. and Frankel, S.( 1957).A colorimetric method for the determination of serum glutamic oxalacetic and glutamic

pyruvic transaminases. AM J Pathol .,28(1):56-63.

Ellefson, R. and Garaway, W. (1976). Lipids and lipoproteins. In: Fundamentals of Clinical Chemistry. Tietz, N.W(Ed) Chap.

: 512-514.

Pearlman, F.C. and Lee, R.T.Y. (1974). Detection and measurement of total bilirubin in serum, with use of surfactants as

solubilizing agents. Clin Chem., 20: 447-453.

Vanuffelen, B. E.; Van Der Zee, J.; De Koster, B .M.; Vansteveninck, J. and Elferink, J .G. (1998). Intracellular but not extracellular conversion of nitroxyl anion into nitric oxide leads to stimulation of human neutrophil migration. Biochem J., 330(2):719-722.

Burtis, C. and Ashwood, E. (1999). Text Book of Clinical Chemistry. 3rd ed. London. Vol.2 Chapter. (33): 1145-1150.

Lee, G. and Luna, L.G. (1968).Manual of histological staining methods of Armed Forces institutes of pathology. 3rded. Mc

Grow-Hill Book Company. New York. Pp: 12-31.

Snedecor, G.W and Cochran, W.G. (1973).Statistical Methods. 6th the Iowa state University press., : 238-248.

Nabavi, S.M.; Nabavi, S.F.; Eslami, S. and Moghaddam, A.H. (2012).In vivo protective effects of quercetin against sodium fluorideinduced oxidative stress in the hepatic tissue. Food Chem. 132: 931–935.

Kushwah, D.S. (2014). Comparison of Ameliorative effects of essential oil and ethanolic extract of Nigella sativa seed in

acetaminophen induced liver damage. Int J Pharm Bio Sci., 5(3):466 – 471.

Maiti, S.K. and Das, P.K. (2004).Biochemical changes in endemic dental fluorosis in cattle. Indian J Anim Sci., 74: 169.

Singh, R. P.; Chidambara, M.K.N. and Jayaprakasha, G. K. (2002). Studies on the antioxidantactivity of pomegranate (Punica

granatum) peel and seed extracts using in vitro models. JAgric Food Chem., 50: 81–86.

Al-Harbi, M. S.; Hamza, R. Z. and Daway, A.A. (2014). Ameliorative effect and curcumin on sodium fluoride induced hepatotoxicity and oxidative stress in male mice. J Chemical and Pharmaceutical Res., 6 (4): 984-998.

Gutowska, I.; Baranowska-Bosiacka, I.; Baśkiewicz, M.; Milo, B.; Siennicka, A.; Marchlewicz, M. and et al. (2010). Fluoride

as a pro-inflammatory factor and inhibitor of ATP bioavailability in differentiated human THP1 monocytic cells. Toxicol. Lett.

: 74-79.

Jacinto-Alemán, L.F.; Hernández-Guerrero, J.C.; TrejoSolís, C.; Jiménez-Farfán, M.D. and FernándezPresas, A.M.(2010). In vitro

effect of sodium fluoride on antioxidative enzymes and apoptosis during murine odontogenesis. J. Oral Pathol Med., 39: 709-714.

Barbier, O.; Mendoza, L.A. and DelRazo, L.M. (2010). Molecular mechanisms of fluoride toxicity. Chem- Biol Interact.,

, 319-333.

Azab, A.E.; Albasha, M.O.; Jbireal, J.M. and Adwas, A.A. (2018) Sodium Fluoride Induces Hepato-Renal Oxidative Stress and

Pathophysiological Changes in Experimental Animals. Open Journal of Apoptosis, 7, 1-23. https://doi.org/10.4236/ojapo.2018.71001.

Osman, M.; Ahmed, M.; Mahfouz, S. and Elaby, S. (2011). Biochemical Studies on the hepatoprotective effects of pomegranate and

guava ethanol extracts. New York Science Journal, 4 (3).

Middha, S.K.; Usha, T. and Pande, V. (2013). A review on antihyperglycemic and antihepatoprotective activity of eco-friendly

Punica granatum peel waste. EvidenceBased Complementary and Alternative Medicine, Vol. 2013:10.

Al-Attar, A.M. (2015). Effect of grape seed oil on diazinon-induced physiological and histopathological alterations in rats. Saudi Journal of Biological Sciences, 22 (3): 284–292.

Khudair, K.K. and Aldabaj, A.M.A. (2014). Effect of high concentration of sodium fluoride on serum lipid profile of male

rabbits: Hypolipidemic effect of grape seed oil. Online Int Interdisciplinary Res J., IV: 17-24.

Czerny, B.; Put, A.; Mysliwiec, Z. and Juzyszyn, Z. (2000).The influence of quercetin on some parameters of lipid metabolism in rats chronically exposed to ammonium fluoride. Fluoride, 33: 127–132.

Rupal A. Vasant, Narasimhacharya AVRL (2012) Ameliorative effect of tamarind leaf on fluoride-induced metabolic alterations.

Environ Health Prev Med. 17:484–493 .

Easterbauer H, Gebick J, Phal H, Jurgens G (1992) the role of lipidperoxidatio- nand antioxidants in the oxidative modifications of

LDL. Free Radic. Biol. Med 13: 341–390.

Machoy-Mokrzynska, A.;Put, A.; Ceglecka, M. and Mys´liwiec, Z.(1994).Influence of essential phospholipids on selected biochemicalparameters of lipid metabolism in rats chronically exposed toammonium fluoride vapours. Fluoride 27 (4):201–204.

Mirmiran, P.; Mohammad, R.F.; Golaleh, A.; Abbas, S and Fereidoun, A (2010).Effect of pomegranate seed on hyperlipidaemic

subjects: A double-blind placebo-controlled clinical trial. Br J Nutr 104(3):402–406.

Esmaillzadeh, A.; Tahbaz, F.; Gaieni, I.; Alavi-Majd, H. and Azadbakht, L. (2006). Cholesterol-lowering effect of concentrated

pomegranate juice consumption in type II diabetic patients with hyperlipidemia, Int J Vitam Nutr Res., 76: 147-151.

Rao, MV.; Vyas, DD.; Meda, RB. and Chawla, SL.(2011). In vitro protection by melatonin against F-induced hemolysis of

RBCs. Fluoride 44(2):77–82.

Gutierrez-Salinas, J.; Zentella, D. M. and Pina .E. (1993). Acute ethanol intake produce lipid peroxidation in rat red blood cells

nembranes . Biochem Mol Biol Inter., 29:263- 270.

Yamaguti, M.P.; Simões, A.; Ganzerla, E.; Souza, N.D.; Nogueira, N.F.and Nicolau, J. (2013). Effects of single exposure of sodium

fluoride on lipid peroxidation and antioxidant enzymes in salivary glands of rats. Oxidative

Medicine and Cellular Longevity, Vol 2013:7.

Sharma, A. and Chinoy, N.J. (1998). Role of free radical in fluoride-induced toxicity in liver and kidney of mice and its reversal.

Fluoride. 31: S26.

Grabowska M, Gumińska M.(1985). Effect of sodium fluoride on magnesium-activated ATPase from human erythrocyte membranes. Folia Med Cracov., 26:29-33.

Bekir, J.; Mars, M.; Vicendo, P.; Fterrich, A. and Bouajila, J. (2013). Chemical composition and antioxidant, antiinflammatory, and antiproliferation activities of pomegranate (Punica granatum) flowers. J Med Food., 16(6):544-50.

Kaur, G.; Jabbar, Z.; Athar, M and Alam, M.S. (2006). Punica granatum (pomegranate) flower extract possesses potent antioxidant

activity and abrogates Fe-NTA induced hepatotoxicity in mice. Food Chem. Toxicol.; 44: 984-993.

Yehia, H.M.; Al-Olayan, E.M. and Elkhadragy, M.F. (2013). Hepatoprotective role of pomegranate (punica granatum) juice

on carbon tetrachloride-induced oxidative in rats. Life Sci J. 10(4): 1534-1544.

Gumus, M.; Tekin, R.; Firal, u.; Onder, A.; Kapan, A.; Boyuk, M.; Aldmir,M. and Kiling, C. (2013). The effect of pomegranate

on bacterial translocation in rats with obstructive jaundice. Eur Rev Med Pharmacol Sci., 17(11): 1488-1494.

Toklu, H.Z.; Dumlu, M.U.; Sehirli, O.; Ercan, F.; Gedik , N.; Gokmen, V and Sener, G.(2007). Pomegranate peel extract prevents

liver fibrosis in biliary obstructed rats .J Pharmacy and Pharmacology, 59(9): 1287-1295.

Kumar, D.; Singh, S.; Singh, A.K. and Rizvi, S.I. (2013). Pomegranate (Punica granatum) peel extract provides protection against

mercuric chloride-induced oxidative stress in wistar strain rats. Pharm Biol., 51 (4): 441-446.

Ashoush, I.S.; El-Batawy, O.I. and ElShourbagy, GA. (2013) Antioxidant activity and hepatoprotective effect of pomegranate

peel and whey powders in rats. Annal Agri Sci., 58(1):27-32.

Vassant, R.A.; Khajuria, M.C. and Narasimhacharya, A.V. (2011). Antioxidant and ACE enhancing potentialof Pankajakasthuri in fluoride toxicity: an invitro study on mammalian lungs. Toxicol IndHealth., 27 (9):793-801.

Hassan, H. A. and Yousef, M. I. (2009). Mitigating effects of antioxidant properties of black berry juice on sodium fluoride induced

hepatotoxicity and oxidative stress in rats. Food and Chemical Toxicology, 47 (9): 2332-2337.

Lu., j.; Lin, PH.; Yao, Q. and Chen, c.(2010).Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J Cell Mol Med. ,14(4): 840–860. doi: 10.1111/j.1582-4934.2009.00897.x.

Bergandi, L.; Aina, V.; Garetto, S.; Malavasi, G.; Aldieri, E.; Laurenti, E.; Matera, L.; Morterra, C. and Ghigo, D. (2010).Fluoridecontaining bioactive glasses inhibit pentose phosphate oxidative pathway and glucose 6-phosphate dehydrogenase activity in human osteoblasts. Chem. Biol. Int., 183: 405–415.

Szabo, C.; Ischiropoulus, H. and Radi, R.(2007). Peroxynitrite: biochemistry, pathophysiology and development of

therapeutics. Nat Rev.,6:662–679.

Pacher, P.; Beckman, J.S and Liaudet, L. (2007): Nitric oxide and peroxynitrite in health and disease. Physiol. Rev.; 87(1): 315-424.

Moneim, E.A. (2012). Antioxidant activities of Punica granatum (pomegranate) peel extract on brain of rats. Journal of Medicinal

Plants Research,6(2): 195-199.

Matthaiou, M.C.; Goutzourelas, N.; Stagos, D.; Sarafoglou, E.; Jamurtas, A.; Koulocheri, S.D.; Haroutounian, S.A.; Tsatsakis, M.A.

and Kouretas, D. (2014). Pomegranate juice consumption increases GSH levels and reduces lipid and protein oxidation in human

blood. Food and Chemical Toxicology, 73 (2014): 1–6.

Ammar, A. ; Turki, M.; Hammouda, O.; Chtourou , H.; Trabelsi, K.; Bouaziz, M.;Abdelkarim, O.; Hoekelmann, A.; Ayadi , F.; Souissi, N.; Bailey, S.J.; Tarak Driss , T. and Yaich, S. (2017). Effects of Pomegranate Juice Supplementation on Oxidative Stress Biomarkers Following Weightlifting Exercise. Nutrients 2017, 9, 819; doi:10.3390/nu9080819