KEY WORDS:Caspase activity Glutathione balance In vitro digestion Neurodegenerative diseases Wild blackberries
1. Hassan HA, Yousef MI. Mitigating effects of antioxidant properties of blackberry juice on sodium fluoride-induced hepatotoxicity and oxidative stress in rats. Food Chem Toxicol 2009;47:2332–7.
2. Chlubek D. Fluoride and oxidative stress. Fluoride 2003;36:217–28.
3. Basha PM, Rai P, Begum S. Fluoride toxicity and status of serum thyroid hormones, brain histopathology, and learning memory in rats: a multigenerational assessment. Biol Trace Elem Res 2011;144:1083–94.
4. Rzeuski R, Chlubek D, Machoy Z. Interactions between fluoride and biological free radical reactions. Fluoride 1998;31:43–5.
5. Shivarajashankara YM, Shivashankara AR, Gopalakrishna BP, Hanumanth RS. Effect of fluoride intoxication on lipid peroxidation and antioxidant systems in rats. Fluoride 2001;34:108–13.
6. Shivarajashankara YM, Shivashankara AR, Hanumanth RS, Gopalakrishna BP. Oxidative stress in children with endemic skeletal fluorosis. Fluoride 2001;34:103–7.
7. Narayanaswamy M, Piler MB. Effect of maternal exposure of fluoride on biometals and oxidative stress parameters in developing CNS of rat. Biol Trace Elem Res 2010;133:71–82.
8. Mullenix PJ, Denbesten PK, Achunior AM, Kernam WJ. Neurotoxicity of sodium fluoride in rats. Neurotoxicol Teratol 1995;17:169–77.
9. Varner JA, Jensen KF, Horvath W, Isaacson RL. Chronic administration of aluminium fluoride and sodium fluoride in rats in drinking water, alterations inneuronal and cerebrovascular integrity. Brain Res 1998;784:284–298.
10. Bhatnagar M, Rao P, Saxena A, Bhatnagar R, Meena P, Barbar S,et al. Biochemical changes in brain and other tissues of young adult female mice from fluoride in their drinking water. Fluoride 2006;39:280–4.
11. Kaur T, Bijarnia RK, Nehru B. Effect of concurrent exposure of fluoride and aluminium on rat brain. Drug Chem Toxicol 2009;32:215–21.
12. Hassan HA, Abdel-Aziz AF. Evaluation of free radical-scavenging and anti-oxidant properties of blackberry against fluoride toxicity in rats. Food Chem Toxicol 2010;48:1999–2004.
13. Altıntas L, Essiz D, Eraslan G, Ince S, Arslanbas E. Prophylactic effect of N-acetylcysteine against sodium fluorideinduced blood oxidative stress in mice. Food Chem Toxicol 2010;48:2838–41.
14. Garcia OB, Castillo J. Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and antiinflammatory activity. J Agric Food Chem 2008;56:6185–205.
15. Facchini PJ, Bird DA, St-Pierre B. Can arabidopsis make complex alkaloids? Trends Plant Sci 2004;9:116–22.
16. Stoner GD. Food stuffs for preventing cancer: the preclinical and clinical development of berries. Cancer Prevent Res 2009;2:187–94.
17. Dunn WB, Ellis DI. Metabolomics: current analytical platforms and methodologies. Trends Anal Chem 2005;24:285–94.
18. Harborne JB, Baxter H. The handbook of natural flavonoids. Chichester, UK: John Wiley & Sons, 1999.
19. Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol 2008;585:325–37.
20. Ghosh D, Das S, Maiti R, Jana D, Das U. Testicular toxicity in sodium fluoride treated rats: association with oxidative stress. Reprod Toxicol 2002;16:385–90.
21. Nabavi SM, Nabavi SF, Eslami S, Moghaddam AH. In vivo protective effects of quercetin against sodium fluoride-induced oxidative stress in the hepatic tissue. Food Chem 2012;132:931–5.
22. Liu CM, Ma JQ, Sun YZ. Quercetin protects the rat kidney against oxidative stress-mediated DNA damage and apoptosis induced by lead. Environ Toxicol Pharmacol 2010;30:264–71.
23. Ismail HA, Hamza RZ, El-Shenawy NS. Potential protective effects of blackberry and quercetin on sodium fluoride-induced impaired hepato-renal biomarkers, sex hormones and hematotoxicity in male rats. J Appl Life Sci Intern 2014;1(1):1–16.
24. Zabulyte D, Uleckiene S, Kalibatas J, Paltanaviciene A,Jascaniniene N, Stosik M. Experimental studies on effect of sodium fluoride and nitrate on biochemical parameters in rats. Bull Vet Inst Pulawy 2007;51:79–82.
25. Seivac FR, Chuffa LG, Bragac CP, Amorima JP, Fernandes AA. Quercetin ameliorates glucose and lipid metabolism and improves antioxidant status in postnatally monosodium glutamate-induced metabolic alterations. Food Chem Toxicol 2012;50:3556–61.
26. Sauebin L, Rossi A, Serraino I. Effect of anthocyanins contained in a blackberry extract on the circulatory failure and multiple organ dysfunction caused by endotoxin in the rat. Planta Med 2004;70:745–52.
27. Siriwoharn T, Wrolstad RE, Finn CE, Pereira CB. Influence of cultivar, maturity, and sampling on blackberry (Rubus L. Hybrids) anthocyanins, polyphenolics, and antioxidant properties. J Agric Food Chem 2004;52:8021–30.
28. Ohkawa H, Ohishi W, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–8.
29. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974;47:469–74.
30. Aebi H. Catalase in vitro. Method Enzymol 1984;105:121–6.
31. Hafeman DG, Sunde RA, Hoekstra WG. Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. J Nutr 1974;104:580–7.
32. Alin P, Danielson UH, Mannervik B. 4-Hydroxyalk-2-enals are substrates for glutathione transferase. FEBS Lett 1985;179:267–70.
33. Prieto P, Pineda M, Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a Phosphomolybdenum complex specific application to the determination of vitamin E. Anal Biochem 1999;269:337–41.
34. Gabe M. Techniques histologiques (Histological Technics).Paris: Masson Publisher, 1968.
35. Halliwell B. Biochemistry of oxidative stress. Biochem Soc Trans 2007;35:1147–50.
36. Shivarajashankara YM, Shivashankara AR, Gopalakrishna BP, Hanumanth RS. Brain lipid peroxidation and antioxidant systems of young rats in chronic fluoride intoxication. Fluoride 2002;35:197–203.
37. Sharma A, Chinoy NJ. Role of free radicals in fluoride-induced toxicity in liver and kidney of mice and its reversal. Fluoride 1998;31:S26.
38. Vani ML, Reddy KP. Effects of fluoride accumulation on some enzymes of brain and gastrocnemius muscle of mice. Fluoride 2000;33:17–26.
39. Liu G, Chai C, Cui L. Fluoride causing abnormally elevated serum nitric oxide levels in chicks. Environ Toxicol Pharmacol 2003;13:199–204.
40. Susheel AK. Fluorosis management programme in India. Curr Sci 1999;77:1250–6.
41. Chinoy NJ, Memon MR. Beneficial effects of some vitamins and calcium on fluoride and aluminum toxicity on gastrocnemius muscle and liver of male mice. Fluoride 2001;34:21–33.
42. Reddy GB, Khandare AL, Reddy PY, Rao GS, Balakrishna N,Srivalli I. Antioxidant defense system and lipid peroxidation in patients with skeletal fluorosis and in fluoride-intoxicated rabbits.Toxicol Sci 2003;72:363–8.
43. Cui Y, Han Y, Yang X, Sun Y, Zhao Y. Protective effects of quercetin and quercetin-5′,8-disulfonate against carbon tetrachloride-caused oxidative liver injury in mice. Molecules 2014;19:291–305.
44. Day AJ, Canada FJ, Diaz JC, Kroon PA, Mclauchlan R, Faulds CB,et al. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett 2000;468:166–70.
45. Klotz LO, Sies H. Defenses against peroxynitrite: seleno compounds and flavonoids. Toxicol Lett 2003;140:125–32.
46. Morales AI, Vicente-Sanchez C, Santiago SJ, Egido J, Mayoral P,Arevalo MA, et al. Protective effect of quercetin on experimental chronic cadmium nephrotoxicity in rats is based on its antioxidant properties. Food Chem Toxicol 2006;442:2092–100.
47. Vicente-Sanchez C, Egido J, Sanchez-Gonzalez PD,Peres-Barriocanal F, Lopez-Novoa JM. Effect of the flavonoid quercetin on cadmium-induced hepatotoxicity. Food Chem Toxicol 2008;46:2279–87.
48. Jiao Z, Liu J, Wang S. Antioxidant activities of total pigment extract from blackberries. Food Technol Biotechnol 2005;43:97–102.
49. Tsuda T. Mechanism for the peroxynitrite scavenging activity by anthocyanins. FEBS Lett 2000;484:207–10.
50. Noda Y. Antioxidant activity of nasunin, an anthocyanin in egg plant peels. Toxicol 2000;148:119–23.
51. Nichenametla SN, Taruscio TG, Barney DL, Exon JH. A review of the effects and mechanisms of polyphenolics in cancer. Crit Rev Food Sci Nutr 2006;46:161–83.
52. Bouaziz H, Soussia L, Guermazi F, Zeghal N, Tunisia S. Fluorideinduced thyroid proliferative changes and their reversal in female mice and their pups. Fluoride 2005;38:207–14.
53. Shashi A, Singh JP, Thapar SP. Toxic effects of fluoride on rabbit kidney. Fluoride 2002;35:38–50.
54. Ramseyer WY, Smith CA, McCay CM. Effect of sodium fluoride administration on body changes in old rats. J Gerontol 1957;12:14–9.
55. Pindbog JJ. The effect of 0.05 percent dietary sodium fluoride in the rat kidney. Acta Pharmacol Toxicol 1957;13:36–45.
56. Chinoy NJ. Fluoride in the environment. In: Chlubek D, editor. Fluoride in medicine, biology and toxicology. Warsaw, Poland: Katedra I Zaklad Biochemii I Chemii Pomorskiej Akademii Medycznej,2003:5–33.
57. Chinoy NJ, Tewari K, Jhala DD. Fluoride and/or arsenic toxicity in mice testis with formation of giant cells and subsequent recovery by some antidotes. Fluoride 2004;37:172–84.
58. Nwaopara AO, Anibeze CI, Akpuaka FC. Histological signs of neurodegeneration in Cerebrum fed with diet containing Yaji: the complex Nigerian Suya meat sauce. Asian J Med Sci2010;2:16–21.
*Corresponding author: Nahla S. El-Shenawy, Faculty of Science,
Zoology Department, Suez Canal University, Ismailia, 41522, Egypt,
Reham Z. Hamza: Faculty of Science, Zoology Department, Zagazig
University, Zagazig, Egypt
Hayat A.A. Ismail: Faculty of Science, Biology Department, King
Abdel Aziz University, Jeddah, Saudi Arabia
ABSTRACT：Background: Sodium fluoride (NaF) intoxication is associated with oxidative stress and altered antioxidant defense mechanism. The present study was carried out to evaluate the potential protective role of blackberry and quercetin (Q) against NaF-induced oxidative stress and histological changes in liver, kidney, testis and brain tissues of rats. Methods: The rats were allocated evenly to seven groups. The first group was maintained as the control, whereas groups 2, 3, 4, 5, 6 and 7 were administered blackberry juice (BBJ), Q, NaF, BBJ+NaF, Q+NaF and BBJ+Q+NaF, respectively, for a period of 30 days. Results and conclusions: NaF caused an elevation in lipid peroxidation level paralleled with significant decline in glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase and catalase activities as well as the total antioxidant activity in liver, kidney, testes and brain. Some histopathological changes were detected in all tested tissues of the NaF treated group. Q and BBJ had successfully maintained normal histological architecture and mitigated the induction of oxidative stress caused by NaF. Q effectively reduced the elevation in thiobarbituric acid reactive substances level and restored the activities of antioxidant enzymes in liver, kidney, testis and brain. Less histopathological changes were observed in Q+NaF and BBJ+NaF treated groups.As a result, BBJ and Q significantly reduced NaF-induced oxidative and histological changes in rats. In the combination of BBJ and Q against NaF toxicity, the effects were more severe than from separate exposure, thus indicating that these flavonoids exhibited synergistic effects on all antioxidant and histological parameters.