Advertisement

Dietary flaxseed oil inhibits kidney NF-kappa B activation and pro-inflammatory cytokine expression in cisplatin-treated rats

  • Hend Samy Kheira
  • Shimaa Abd El-Salam El-Sayed
  • Gehad Ramadan Elsayed
  • Mohamed Abdo Rizk
Original Article
  • 16 Downloads

Abstract

The current study explores the anti-inflammatory effect of flaxseed oil (FXO) on cisplatin (CP)-induced renal damage. Rats prefed with normal experimental diets (normal/FXO diet) for 10 days were administered 30 mg kg−1 and 50 mg kg−1 i.p. CP in a single dose, while still on the experimental diets. Significant improvement in kidney function test and antioxidant enzyme activities in rats treated with combination therapy (FXO + CP) was detected. Interestingly, treatment by FXO resulted in significant downregulation (P < 0.05) in interleukin (IL)-6 and IL-1β expression in the renal tissue in comparison with CP-treated rats. Moreover, administration of FXO yielding negative and mild positive brown immunostain for tumor necrosis factor-alpha (TNF-α) or mild and moderate positive brown immunostain for nuclear factor Kappa B (NF-kB) in the renal tissue of rats treated with 3 mg kg−1 CP + FXO and 5 mg kg−1 CP + FXO, respectively. The obtained results highlight the ameliorative anti-inflammatory effect of FXO in the renal damage associated with CP administration and confirm the necessity and usefulness of FXO dietary supplement when using CP in the treatment of cancer patients.

Keywords

Cisplatin Flaxseed oil Nephrotoxicity Pro-inflammatory cytokines 

Notes

Author contributions

Conceived and designed the experiments: HSK, SAE, GRE. Performed the experiments: HSK, SAE. Analyzed the data: MAR. Wrote and revised the paper: HSK, SAE, GRE, MAR.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

580_2018_2871_MOESM1_ESM.pptx (784 kb)
Figure S1 Fold change in β-actin gene expression in RT-PCR showing the effect of FXO on kidney with/without CP treatment (PPTX 783 kb)
580_2018_2871_MOESM2_ESM.pptx (755 kb)
Figure S2 Fold change in IL-6 gene expression in RT-PCR showing the effect of FXO on kidney with/without CP treatment (PPTX 755 kb)
580_2018_2871_MOESM3_ESM.pptx (798 kb)
Figure S3 Fold change in IL-1β gene expression in RT-PCR showing the effect of FXO on kidney with/without CP treatment. (PPTX 797 kb)

References

  1. Abdel-Moniem AE, Dkhil MA, Al-Quraishy S (2011) The potential role of flaxseed oil on lead acetate induced kidney injure in adult male albino rats. Afr J Biotechnol 10:1436–1451Google Scholar
  2. Aggarwal BB, Samanta A, Feldmann M (2001) NFα. In: Oppenheim, Feldmann M (eds) Cytokine reference, vol 1. Academic Press, San Diego, pp 413–434Google Scholar
  3. Ali BH, Al Moundhri SM (2006) Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: a review of some recent research. Food Chem Toxicol 44:1173–1183CrossRefGoogle Scholar
  4. Al-Majed AA, Sayed-Ahmed MM, Al-Yahya AA, Aleisa AM, Al- Rejaie SS, Al-Shabanah OA (2006) Propionyl-L-carnitine prevents the progression of cisplatin-induced cardiomyopathy in a carnitine-depleted rat model. Pharmacol Res 53:278–286CrossRefGoogle Scholar
  5. Arany I, Safirstein RL (2003) Cisplatin nephrotoxicity. Semin Nephrol 23:460–464CrossRefGoogle Scholar
  6. Atessahin A, Yilmaz S, Karahan I, Ceribasi AO, Karaoglu A (2005) Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress in rats. Toxicology 212:116–123CrossRefGoogle Scholar
  7. Baldie G, Kaimakamis D, Rotondo D (1993) Fatty acid modulation of cytokine release from human monocytic cells. Biochimica et Biophysica Acta 1179:125–133CrossRefGoogle Scholar
  8. Banni M, Messaoudi I, Said L, Heni J, Kerkeni A, Said K (2010) Metallothionein gene expression in liver of rats exposed to cadmium and supplemented with zinc and selenium. Arch Environ Contam Toxicol 59:513–519CrossRefGoogle Scholar
  9. Begue G, Douillard A, Galbes O, Rossano B, Vernus B, Candau R, Py G (2013) Early activation of rat skeletal muscle IL-6/STAT1/STAT3 dependent gene expression in resistance exercise linked to hypertrophy. PLoS One 8:e57141CrossRefGoogle Scholar
  10. Calder PC (2001) Omega 3 polyunsaturated fatty acids, inflammation and immunity. World Rev Nutr Diet 88:109–116CrossRefGoogle Scholar
  11. Cetin R, Devrim E, Killicoglu B, Avci A, Candir O, Durak I (2006) Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues: possible protective roles of natural antioxidant foods. J Appl Toxicol 26:42–46CrossRefGoogle Scholar
  12. Deng J, Kohda Y, Chiao H, Wang Y, Hu X, Stephen M, Hewitt MT, Mc Leroy P, Nibhanupudy B, Li S, Robert A, Star (2001) Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. Kidney Int 60:2118–2128CrossRefGoogle Scholar
  13. Desoize B, Madoulet C (2002) Particular aspects of platinum compounds used at present in cancer treatment. Crit Rev Oncol Hematol 42:317–325CrossRefGoogle Scholar
  14. Dos-Santos NA, Martins NM, Curti C, Pires Bianchi ML, Dos Santos AC (2007) Dimethylthiourea protects against mitochondrial oxidative damage induced by cisplatin in liver of rats. Chem Biol Interact 170:177–186CrossRefGoogle Scholar
  15. Ebling WF, Danhof M, Stanski DR (1991) Pharmacodynamic characterization of the electroencephalographic effects of thiopental in rats. J Pharmacokinet Biophar 19:123–143CrossRefGoogle Scholar
  16. Florea AM, Büsselberg D (2006) Metals and metal compounds: occurrence, use, benefits and toxic cellular effects. Biometals 19:419–427CrossRefGoogle Scholar
  17. Gonzales R, Romay C, Borrego A, Hernandez F, Zamora Z, Rojas E (2005) Lipid peroxides and antioxidant enzymes in cisplatin chronic nephrotoxicity in rats. Mediat Inflamm 3:139–143CrossRefGoogle Scholar
  18. Khan SA, Priyamvada S, Khan W, Khan S, Farooq N, Yusufi ANK (2009) Studies on the protective effect of green tea extract against cisplatin-induced nephrotoxicity. Pharmacol Res 60:382–391CrossRefGoogle Scholar
  19. Mills SC, Windsor AC, Knight SC (2005) The potential interactions between polyunsaturated fatty acids and colonic inflammatory processes. Clin Exp Immunol 142:216–228CrossRefGoogle Scholar
  20. Naqshbandi A, Wasim MD, Sana R, Khan F (2012) Studies on the protective effect of flaxseed oil on cisplatin-induced hepatotoxicity. Hum Exp Toxicol 4:364–375CrossRefGoogle Scholar
  21. Naqshbandi A, Sana R, Khan F (2013) Dietary supplementation of flaxseed oil ameliorates the effect of cisplatin on rat kidney. J Funct Foods 5:316–326CrossRefGoogle Scholar
  22. Newairy AS, Abdou HM (2009) Protective role of flax lignans against lead acetate induced oxidative damage and hyperlipidemia in rats. Food Chem Toxicol 47:813–818CrossRefGoogle Scholar
  23. Nishikimi M, Roa NA, Yogi K (1972) The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun 46:849–854CrossRefGoogle Scholar
  24. Ohkawa H, Ohishi W, Yagi K et al (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Biochem 95:351–358Google Scholar
  25. Ozgocmen S, Atalay Catal S, Ardıçoğlu Ö, Kamanli A (2000) Effect of omega-3 fatty acids in the management of fibromyalgia syndrome. Int J Clin Pharm Ther 38:362–363CrossRefGoogle Scholar
  26. Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169PubMedGoogle Scholar
  27. Pedersen BK (2000) Special feature for the Olympics: effects of exercise on the immune system. Immunol Cell Biol 78:532–535CrossRefGoogle Scholar
  28. Ramesh G, Reeves WB (2002) TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J Clin Invest 110:835–842​CrossRefGoogle Scholar
  29. Ramesh G, Zhang B, Uematsu S, Akira S, Reeves WB (2007) Endotoxin and cisplatin synergistically induce renal dysfunction and cytokine production in mice. Am J Physiol Renal Physiol 293:F325–F332CrossRefGoogle Scholar
  30. Rizk MA, El-Sayed SAE-S, Terkawi MA, Youssef MA, El Said ESES, Elsayed G, El-Khodery S, Al-Ashker M, Elsify A, Omar M, Salama A, Yokoyama N, Igarashi I (2015) Optimization of a fluorescence−based assay for large-scale drug screening against Babesia and Theileria parasites. PLoS One 10:e0125276CrossRefGoogle Scholar
  31. Rizk MA, El-Sayed SA, AbouLaila M, Yokoyama N, Igarashi I (2016) Large-scale drug screening against Babesia divergens parasite using a fluorescence-based high- throughput screening assay. Vet Parasitol 227:93–97CrossRefGoogle Scholar
  32. Rizk MA, El-Sayed SAE, AbouLaila M, Yokoyama N, Igarashi I (2017) Performance and consistency of a fluorescence-based high-throughput screening assay for use in Babesia drug screening in mice. Sci Rep 7:12774CrossRefGoogle Scholar
  33. Rizk MA, AbouLaila M, El-Sayed SAE, Guswanto A, Yokoyama N, Igarashi I (2018) Inhibitory effects of fluoroquinolone antibiotics on Babesia divergens and Babesia microti, blood parasites of veterinary and zoonotic importance. Infect Drug Resist 11:1605–1615CrossRefGoogle Scholar
  34. Robert D, Lee M K-e, Abraham TK et al (1987) Inhibition of cisplatin-induced nephrotoxicity in rats by buthionine sulfoximine, a glutathione synthesis inhibitor. Cancer Chemother Pharmacol 20:207–210CrossRefGoogle Scholar
  35. Saad SY, Arafah MM, Najjar TA (2007) Effects of mycophenolate mofetil on cisplatin induced renal dysfunction in rats. Cancer Chem Pharmacol 59:455–460CrossRefGoogle Scholar
  36. Shah N, Dizon DS (2009) New-generation platinum agents for solid tumors. Future Oncol 5:33–42CrossRefGoogle Scholar
  37. Sung MJ, Kim DH, Jung YJ (2008) Genitein protect the kidney fromcisplatin-induced injury. Kidney Int 74:1538–1547CrossRefGoogle Scholar
  38. Tsang RY, Al-Fayea T, Au HJ (2009) Cisplatin overdose: toxicities and management. Drug Saf 32:1109–1122CrossRefGoogle Scholar
  39. Wahba HM, Ibrahim TA (2013) Protective effect of flaxseed oil and vitamin E on potassium bromate-induced oxidative stress in male rats. Int J Curr Microbiol App Sci 2:299–309Google Scholar
  40. Wang CX, Olschowka JA, Wrathall JR (1997) Increase of interleukin-1b mRNA and protein in the spinal cord following experimental traumatic injury in the rat. Brain Res 759:190–196CrossRefGoogle Scholar
  41. Williams DS, Verghese M, Walker LT, Boateng J et al (2008) Chemopreventive effects of flaxseed oil and flax seed meal on azoxymethane-induced colon tumors in fisher 344 male rats. Int J Cancer Res 2:28–40Google Scholar
  42. Young DS (2001) Effects of disease on clinical lab. Tests, 4th ed AACCGoogle Scholar
  43. Yuan JS, Reed A, Stewart CN Jr (2006) Statistical analysis of real-time PCR data. BMC Bioinformatics 22;7:85CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary MedicineMansoura UniversityMansouraEgypt
  2. 2.Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary MedicineMansoura UniversityMansouraEgypt

Personalised recommendations