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Sources of Funding: College of Medicine & Health Sciences, United Arab Emirates University

Introduction

Renal ischemia-reperfusion injury (IRI) is an invariable consequence of several urological conditions and procedures and is associated with alterations in renal functions._x000D_ Recently, there has been a growing interest in using natural phytochemical compounds as treatment alternatives to conventional drugs in several diseases. This is due to their relatively low toxicity and price and to wide availability. Thymoquinone, an antioxidant phytochemical compound found in the plant Nigella sativa which is heavily consumed in some parts of the world, has been shown to have a protective effect in several renal conditions. However, its effect on the IRI-induced renal hemodynamic and tubular dysfunction has not been investigated yet. Thus, the aim of this study was to investigate the effect of thymoquinone on the alterations in renal functional parameters following warm IRI in the rat_x000D_

Methods

Wistar rats underwent left renal ischemia for 35 minutes. Group-TQ (n=15) received thymoquinone 10 mg/kg/day (dissolved in a vehicle (corn oil) orally by gavage starting 4 days prior to the IRI and continued 6 days thereafter when the renal functions of the right and left kidneys were measured using clearance techniques. Group-Vx (n=15) underwent similar protocol but received only the vehicle. In addition, gene expression of some markers of kidney injury and cytokines was measured in the kidney tissue using PCR technique

Results

IRI affected all hemodynamic and tubular parameters in the affected kidney. So in Group-Vx, the left renal blood flow (RBF), six days following IRI, was 22% of the right RBF (1.27±0.21 vs. 5.77±0.54, P=0.0001). Similarly, the left kidney glomerular filtration rate (GFR) was 15% that of the right non-ischemic kidney (0.18±0.03 vs. 1.22±0.07, P=0.0001). On the other hand, the fractional excretion of sodium (FENa) in the left kidney was significantly higher than the right kidney (2.40±0.35 vs. 0.59±0.08, P=0.0001). When the right non-ischemic kidneys in both groups were compared, all the variables were similar._x000D_ Thymoquinone attenuated the IRI-related alteration in renal functions so when the left ischemic kidney in Group-TQ and Group-Vx were compared, the left RBF and GFR were significantly higher in Group-TQ (2.02±0.39 vs. 1.27±0.21, P=0.04 and 0.33±0.08 vs. 0.18±0.03, P=0.03, respectively). On the other hand, the left renal FENa was significantly lower in Group-TQ (1.59±0.28 vs. 2.40±0.35, P=0.04). Thymoquinone also decreased the gene expressions of KIM-1, NGAL, TNF-α, TGF-β1 and PAI-1 (143±20 vs. 358±49, 16±3 vs. 34±6, 1.1±0.2 vs. 2.8±0.4, 1.6±0.1 vs. 2.8±0.1, and 2.4±0.3 vs. 5.8±1.0, P<0.05 for all)._x000D_

Conclusions

Thymoquinone ameliorated the IRI effect on the hemodynamic and tubular renal functional parameters as well as the expression of some markers of renal injury and pro-inflammatory and pro-fibrotic cytokines indicating a renoprotective effect of this agent on the IRI-induced renal dysfunction with potential clinical implications.

Funding

College of Medicine & Health Sciences, United Arab Emirates University