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First published online April 28, 2015

The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles

Abstract

Particulate air pollution (PAP) exposure is associated with increased morbidity and mortality, particularly in patients with renal disease. However, there are only a few studies on the interaction between PAP and renal injury, and none on agents that may ameliorate it. We studied the interaction between cisplatin (CP) nephrotoxicity and a single exposure to diesel exhaust particle (DEP) in rats 24 h before sacrifice, and assessed the effect of co-treatment with the active ingredient in Nigella Sativa seed oil, thymoquinone (TQ) thereon. Rats were injected intraperitoneally with CP (6 mg/kg) and four days later, they were exposed intratracheally to DEP (0.5 mg/kg), and were sacrificed 24 h later. Oral TQ (20 mg/kg) was given daily throughout the experimental period. CP alone caused several physiological, biochemical, and histopathological changes that included reduced growth and creatinine clearance, and raised plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6) and C-reactive protein (CRP), creatinine and urea concentrations, and urinary N-acetyl-b-D-glucosaminidase (NAG) activities. It adversely affected several indices of oxidative damage in the kidneys, and induced renal tubular necrosis. Most of these actions were significantly potentiated in rats given both CP and DEP. TQ significantly abrogated many of the effects of CP and DEP, given alone and in combination. These results provide experimental evidence that subjects with renal diseases can be at higher risk from PAP, and that TQ, pending further pharmacological and toxicological studies, can be considered a useful agent in patients with renal diseases and exposed to PAP.

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References

1. Fury MG, Sherman E, Ho AL, Xiao H, Tsai F, Nwankwo O, Sima C, Heguy A, Katabi N, Haque S, Pfister DG. A phase 1 study of everolimus plus docetaxel plus cisplatin as induction chemotherapy for patients with locally and/or regionally advanced head and neck cancer. Cancer 2013; 119: 1823–31.
2. Nicholson S, Hall E, Harland SJ, Chester JD, Pickering L, Barber J, Elliott T, Thomson A, Burnett S, Cruickshank C, Carrington B, Waters R, Bahl A. Phase II trial of docetaxel, cisplatin and 5FU chemotherapy in locally advanced and metastatic penis cancer (CRUK/09/001). Br J Cancer 2013; 109: 2554–9.
3. Máthé C, Bohács A, Duffek L, Lukácsovits J, Komlosi ZI, Szondy K, Horváth I, Müller V, Losonczy G. Cisplatin nephrotoxicity aggravated by cardiovascular disease and diabetes in lung cancer patients. Eur Respir J 2011; 3: 888–94.
4. Stathopoulos GP. Cisplatin: Process and future. J BUON 2013; 18: 564–9.
5. Yao X, Panichpisal K, Kurtzman N, Nugent K. Cisplatin nephrotoxicity: A review. Am J Med Sci 2007; 334: 115–24.
6. Boulikas T, Vougiouka M. Cisplatin and platinum drugs at the molecular level. (Review). Oncol Rep 2003; 10: 1663–82.
7. Sánchez-González PD, López-Hernández FJ, López-Novoa JM, Morales AI. An integrative view of the pathophysiological events leading to cisplatin nephrotoxicity. Crit Rev Toxicol 2011; 41: 803–821.
8. Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of Cisplatin nephrotoxicity. Toxins (Basel) 2010; 2: 2490–518.
9. dos Santos NA, Carvalho Rodrigues MA, Martins NM, dos Santos AC. Cisplatin-induced nephrotoxicity and targets of nephroprotection: An update. Arch Toxicol 2012; 86: 1233–50.
10. Chirino YI, Pedraza-Chaverri J. Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol 2009; 61: 223–42.
11. Koyner JL, Sher Ali R, Murray PT. Antioxidants. Do they have a place in the prevention or therapy of acute kidney injury?. Nephron Exp Nephrol 2008; 109: e109–17.
12. Pabla N, Dong Z. Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies. Kidney Int 2008; 73: 994–1007.
13. Hanigan MH, Townsend DM, Cooper AJ. Metabolism of cisplatin to a nephrotoxin. Toxicology 2009; 257: 174–175.
14. Ali BH, Al Moundhri MS. Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: A review of some recent research. Food Chem Toxicol 2006; 44: 1173–83.
15. Ali BH, Al-Moundhri M, Eldin MT, Nemmar A, Al-Siyabi S, Annamalai K. Amelioration of cisplatin-induced nephrotoxicity in rats by tetramethylpyrazine, a major constituent of the Chinese herb Ligusticum wallichi. Exp Biol Med (Maywood) 2008; 233: 891–6.
16. Ali BH, Al-Salam S, Al Husseini IS, Al-Lawati I, Waly M, Yasin J, Fahim M, Nemmar A. Abrogation of cisplatin-induced nephrotoxicity by emodin in rats. Fundam Clin Pharmacol 2013; 27: 192–200.
17. Al-Kharusi N, Babiker HA, Al-Salam S, Waly MI, Nemmar A, Al-Lawati I, Yasin J, Beegam S, Ali BH. Ellagic acid protects against cisplatin-induced nephrotoxicity in rats: A dose-dependent study. Eur Rev Med Pharmacol Sci 2013; 17: 299–310.
18. Nemmar A, Holme JA, Rosas I, Schwarze PE, Alfaro-Moreno E. Recent advances in particulate matter and nanoparticle toxicology: a review of the in vivo and in vitro studies. Biomed Res Int 2013;2013:279371.
19. Nemmar A, Al-Salam S, Zia S, Marzouqi F, Al-Dhaheri A, Subramaniyan D, Dhanasekaran S, Yasin J, Ali BH, Kazzam EE. Contrasting actions of diesel exhaust particles on the pulmonary and cardiovascular systems and the effects of thymoquinone. Br J Pharmacol 2011; 164: 1871–1882.
20. Li PK, Burdmann EA, Mehta RL. World Kidney Day Steering Committee 2013. Acute kidney injury: global health alert. Transplantation 2013; 95: 653–7.
21. Peng Q, Zhang L, Ai Y, Zhang L. Epidemiology of acute kidney injury in intensive care septic patients based on the KDIGO guidelines. Chin Med J (Engl) 2014; 127: 1820–6.
22. Perazella MA. Onco-nephrology: Renal toxicities of chemotherapeutic agents. Clin J Am Soc Nephrol 2012; 7: 1713–21.
23. Burki TK. Twice as bad: New estimates for mortality from air pollution. Lancet Respir Med 2014; 2: 355.
24. Atkinson RW, Kang S, Anderson HR, Mills IC, Walton HA. Epidemiological time series studies of PM2.5 and daily mortality and hospital admissions: A systematic review and meta-analysis. Thorax 2014; 69: 660–5.
25. Ali BH. The effect of Nigella sativa oil on gentamicin nephrotoxicity in rats. Am J Chin Med 2004; 32: 49–55.
26. Zang D, Shao Y, Li X. Ultrastructural pathology of rat lung injury induced by ischemic acute kidney injury. Ultrastruct Pathol 2013; 37: 433–9.
27. Pierson DJ. Respiratory considerations in the patient with renal failure. Respir Care 2006; 51: 413–22.
28. Chien CC, King LS, Rabb H. Mechanisms underlying combined acute renal failure and acute lung injury in the intensive care unit. Contrib Nephrol 2004; 144: 53–62.
29. Hassoun HT, Lie ML, Grigoryev DN, Liu M, Tuder RM, Rabb H. Kidney ischemia-reperfusion injury induces caspase-dependent pulmonary apoptosis. Am J Physiol Renal Physiol 2009; 297: F125–37.
30. Laden F, Winkelmayer WC. Air pollution and coronary risk in kidney transplant recipients. Am J Kidney Dis 2011; 58: 506–7.
31. Mansour MA, Nagi MN, El-Khatib AS, Al-Bekairi AM. Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase in different tissues of mice: a possible mechanism of action. Cell Biochem Funct 2002; 20: 143–51.
32. Ali BH, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Phytother Res 2003; 17: 299–305.
33. Woo CC, Kumar AP, Sethi G, Tan KH. Thymoquinone: Potential cure for inflammatory disorders and cancer. Biochem Pharmacol 2012; 83: 443–51.
34. Aycan IÖ, Tüfek A, Tokgöz O, Evliyaoğlu O, Fırat U, Kavak GÖ, Turgut H, Yüksel MU. Thymoquinone treatment against acetaminophen-induced hepatotoxicity in rats. Int J Surg 2014; 12: 213–8.
35. Bai T, Yang Y, Wu YL, Jiang S, Lee JJ, Lian LH, Nan JX. Thymoquinone alleviates thioacetamide-induced hepatic fibrosis and inflammation by activating LKB1-AMPK signaling pathway in mice. Int Immunopharmacol 2014; 19: 351–7.
36. Ali BH, Al Salam S, Al Za'abi M, Al Balushi K, AlMahruqi AS, Beegam S, Al-Lawatia I, Waly MI, Nemmar A. Renoprotective effects of gamma-aminobutyric acid (GABA) on cisplatin-induced acute renal injury in rats. Basic Clin Pharmacol Toxicol 2015; 35: 29–37.
37. Esteban-Fernández D, Verdaguer JM, Ramírez-Camacho R, Palacios MA, Gómez-Gómez MM. Accumulation, fractionation, and analysis of platinum in toxicologically affected tissues after cisplatin, oxaliplatin, and carboplatin administration. J Anal Toxicol 2008; 32: 140–6.
38. Abdelrahman AM, Al Salam S, AlMahruqi AS, Al husseni IS, Mansour MA, Ali BH. N-acetylcysteine improves renal hemodynamics in rats with cisplatin-induced nephrotoxicity. J Appl Toxicol 2010; 30: 15–21.
39. Ali BH, Abdelrahman AM, Al-Salam S, Sudhadevi M, AlMahruqi AS, Al-Husseni IS, Beegam S, Dhanasekaran S, Nemmar A, Al-Moundhri M. The effect of sildenafil on cisplatin nephrotoxicity in rats. Basic Clin Pharmacol Toxicol 2011; 109: 300–8.
40. Do Amaral CL, Francescato HD, Coimbra TM, Costa RS, Darin JD, Antunes LM, Bianchi Mde L. Resveratrol attenuates cisplatin-induced nephrotoxicity in rats. Arch Toxicol 2008; 82: 363–70.
41. Nemmar A, Beegam S, Yuvaraju P, Yasin J, Fahim MA, Kazzam EE, Alhaddabi I, Ali BH. Potentiation of cisplatin-induced nephrotoxicity by repeated exposure to diesel exhaust particles: An experimental study in rats. Exp Biol Med (Maywood) 2014; 239: 1036–44.
42. Sahu BD, Kalvala AK, Koneru M, Mahesh Kumar J, Kuncha M, Rachamalla SS, Sistla R. Ameliorative effect of fisetin on cisplatin-induced nephrotoxicity in rats via modulation of NF-κB activation and antioxidant defence. PLoS One 2014; 9: e105070.
43. Liu Y, Webb HK, Fukushima H, Micheli J, Markova S, Olson JL, Kroetz DL. Attenuation of cisplatin-induced renal injury by inhibition of soluble epoxide hydrolase involves nuclear factor κB signaling. J Pharmacol Exp Ther 2012; 341: 725–34.
44. Al-Malki AL, Sayed AA. Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa-β. BMC Complement Altern Med 2014; 14: 282.
45. Galaly SR, Ahmed OM, Mahmoud AM. Thymoquinone and curcumin prevent gentamicin-induced liver injury by attenuating oxidative stress, inflammation and apoptosis. J Physiol Pharmacol 2014; 65: 823–32.

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Published In

Article first published online: April 28, 2015
Issue published: December 2015

Keywords

  1. Cisplatin
  2. diesel exhaust particle
  3. nephrotoxicity
  4. thymoquinone
  5. rats

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© 2015 by the Society for Experimental Biology and Medicine.

Authors

Affiliations

Badreldin H Ali
Departments of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod 123, Oman
Mohammed Al Za'abi
Departments of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod 123, Oman
Asem Shalaby
Department of Pathology, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod 123, Oman
Priyadarsini Manoj
Departments of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod 123, Oman
Mostafa I Waly
Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al Khod 123, Oman
Javed Yasin
Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
Mohamed Fahim
Departments of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
Abderrahim Nemmar
Departments of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

Notes

Badreldin H Ali. Emails: [email protected]; [email protected]

Authors' Contributions

Conceived and designed the experiments: BHA. Performed the experiments: MZ, ES, PM, MIW, JY, AN, MF. Analyzed the data: BHA, MZ, AN. Wrote the MS: BHA. Revised the MS: MZ, AN. All authors read and approved the submission.

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