Background: Gentamicin (GEN) is considered as a main aminoglycoside antibiotic medicine. The top therapeutic side effect of GEN is nephrotoxicity. The current research was proposed to determine the protective effect of thymoquinone (TQ) on GEN-induced acute renal failure (ARF). Methods: The rats were divided into 6 groups: sham group, control group, GEN-treated group and the TQ-treated groups. At the end of the research period, the serum blood urea nitrogen (BUN) and creatinine (Cr) were measured. The kidneys were then removed for evaluating malondialdehyde (MDA), reduced glutathione (GSH), interleukins IL-6, IL-10, IL-18 and IL-1β, tumor necrosis factor α (TNF-α), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. Results: GEN induced a raise in the levels of serum Cr, BUN and also the levels of MDA, IL-6, IL-18, IL-1β and TNF-α with decease in GSH, SOD, GPx and IL-10 in the kidney (p < 0.05). The data illustrated that the significant elevation in the levels of serum Cr, BUN, MDA, IL-6, IL-18, IL-1β, TNF-α and also the reduction of GSH, SOD, SOD, GPx, IL-10 in the kidney were ameliorated in the TQ-treated groups versus the untreated group, in a dose-dependent manner (p < 0.05). Conclusion: The present investigation proposes that TQ may be ameliorated ARF through modulation of the oxidative stress and inflammatory responses.

1.
Sahu BD, Kuncha M, Putcha UK, Sistla R: Effect of metformin against cisplatin induced acute renal injury in rats: a biochemical and histoarchitectural evaluation. Exp Toxicol Pathol 2013;65:933-940.
2.
Parlakpinar H, Tasdemir S, Polat A, Bay-Karabulut A, Vardi N, Ucar M, et al: Protective role of caffeic acid phenethyl ester (CAPE) on gentamicin-induced acute renal toxicity in rats. Toxicology 2005;207:169-177.
3.
Erdem A, Gundogan NU, Usubutun A, Kilinc K, Erdem SR, Kara A, et al: The protective effect of taurine against gentamicin-induced acute tubular necrosis in rats. Nephrol Dial Transplant 2000;15:1175-1182.
4.
Akcay A, Nguyen Q, Edelstein CL: Mediators of inflammation in acute kidney injury. Mediators Inflamm 2009;2009:137072.
5.
Balakumar P, Rohilla A, Thangathirupathi A: Gentamicin-induced nephrotoxicity: do we have a promising therapeutic approach to blunt it? Pharmacol Res 2010;62:179-186.
6.
Samarghandian S, Azimi-Nezhad M, Samini F: Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin induced experimental diabetes mellitus. Biomed Res Int 2014;2014:920857.
7.
Samarghandian S, Borji A, Delkhosh MB, Samini F: Safranal treatment improves hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats. J Pharm Pharm Sci 2013;16:352-362.
8.
Samarghandian S, Borji A, Tabasi SH: Effects of Cichorium intybus linn on blood glucose, lipid constituents and selected oxidative stress parameters in streptozotocin-induced diabetic rats. Cardiovasc Hematol Disord Drug Targets 2013;13:231-236.
9.
Samarghandian S, Hadjzadeh MA, Amin Nya F, Davoodi S: Antihyperglycemic and antihyperlipidemic effects of guar gum on streptozotocin-induced diabetes in male rats. Pharmacogn Mag 2012;8:65-72.
10.
Al-Ghamdi MS: The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol 2001;76:45-48.
11.
Badary OA, Taha RA, Gamal el-Din AM, Abdel-Wahab MH: Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol 2003;26:87-98.
12.
Genet S, Kale RK, Baquer NZ: Alterations in antioxidant enzymes and oxidative damage in experimental diabetic rat tissues: effect of vanadate and fenugreek (Trigonellafoenum graecum). Mol Cell Biochem 2002;236:7-12.
13.
Gupta A, Gupta A, Nigam D, Shukla GS, Agarwal AK: Profile of reactive oxygen species generation and antioxidative mechanisms in the maturing rat kidney. J Appl Toxicol 1999;19:55-59.
14.
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;47:469-474.
15.
Paglia DE, Valentine WN: Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158-169.
16.
Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-254.
17.
Stojiljkovic N, Stoiljkovic M, Mihailovic D, Randjelovic P, Ilic S, Gocmanac-Ignjatovic M, Veljkovic M: Beneficial effects of calcium oral coadministration in gentamicin-induced nephrotoxicity in rats. Ren Fail 2012;34:622-627.
18.
Balakumar P, Rohilla A, Thangathirupathi A: Gentamicin-induced nephrotoxicity: do we have a promising therapeutic approach to blunt it? Pharmacol Res 2010;62:179-186.
19.
Bledsoe G, Crickman S, Mao J, Xia CF, Murakami H, Chao L, Chao J: Kallikrein/kinin protects against gentamicin-induced nephrotoxicity by inhibition of inflammation and apoptosis. Nephrol Dial Transplant 2006;21:624-633.
20.
Al-Majed AA, Mostafa AM, Al-Rikabi AC, Al-Shabanah OA: Protective effects of oral arabic gum administration on gentamicin-induced nephrotoxicity in rats. Pharmacol Res 2002;46:445-451.
21.
Jia P, Teng J, Zou J, Fang Y, Jiang S, et al: Intermittent exposure to xenon protects against gentamicin-induced nephrotoxicity. PLoS One 2013;8:e64329.
22.
Polat A, Parlakpinar H, Tasdemir S, Colak C, Vardi N, Ucar M, Emre MH, Acet A: Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats. Acta Histochem 2006;108:365-371.
23.
Kalayarasan S, Prabhu PN, Sriram N, Manikandan R, Arumugam M, Sudhandiran G: Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats. Eur J Pharmacol 2009;606:162-171.
24.
Mansour MA, Mostafa AM, Nagi MN, Khattab MM, Al-Shabanah OA: Protective effect of aminoguanidine against nephrotoxicity induced by cisplatin in normal rats. Comp Biochem Physiol C Toxicol Pharmacol 2002;132:123-128.
25.
Ali BH, Al Za'abi M, Blunden G, Nemmar A: Experimental gentamicin nephrotoxicity and agents that modify it: a mini-review of recent research. Basic Clin Pharmacol Toxicol 2011;109:225-232.
26.
Badary OA: Thymoquinone attenuates ifosfamide-induced Fanconi syndrome in rats and enhances its antitumor activity in mice. J Ethnopharmacol 1999;67:135-142.
27.
Romero F, Perez M, Chavez M, Parra G, Durante P: Effect of uric acid on gentamicin-induced nephrotoxicity in rats - role of matrix metalloproteinases 2 and 9. Basic Clin Pharmacol Toxicol 2009;105:416-424.
28.
Badary OA, Taha RA, Gamal el-Din AM, Abdel-Wahab MH: Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol 2003;26:87-98.
29.
Simmons EM, Himmelfarb J, Sezer MT, et al: Plasma cytokine levels predict mortality in patients with acute renal failure. Kidney Int 2004;65:1357-1365.
30.
Friedewald JJ, Rabb H: Inflammatory cells in ischemic acute renal failure. Kidney Int 2004;66:486-491.
31.
Ramesh G, Reeves WB: TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J Clin Invest 2002;110:835-842.
32.
Donnahoo KK, et al: Early kidney TNF-alpha expression mediates neutrophil infiltration and injury after renal ischemia-reperfusion. Am J Physiol 1999;277(3 pt 2):R922-R929.
33.
Sahu BD, Tatireddy S, Koneru M, Borkar RM, Kumar JM, Kuncha M, Srinivas R, Shyam Sunder R, Sistla R: Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection. Toxicol Appl Pharmacol 2014;277:8-20.
34.
Deng J, Kohda Y, Chiao H, et al: Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. Kidney Int 2001;60:2118-2128.
35.
Sayed-Ahmed MM, Nagi MN: Thymoquinone supplementation prevents the development of gentamicin-induced acute renal toxicity in rats. Clin Exp Pharmacol Physiol 2007;34:399-405.
36.
Nagi MN, Mansour MA: Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol Res 2000;41:283-289.
37.
Ragheb A, Attia A, Eldin WS, Elbarbry F, Gazarin S, Shoker A: The protective effect of thymoquinone, an anti-oxidant and anti-inflammatory agent, against renal injury: a review. Saudi J Kidney Dis Transpl 2009;20:741-752.
38.
Al-Malki AL, Sayed AA: Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa-β. BMC Complement Altern Med 2014;14:282.
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