Thymoquinone and curcumin attenuate gentamicin-induced renal oxidative stress, inflammation and apoptosis in rats

Abstract

The present study was aimed to investigate the possible protective effects of thymoquinone (TQ) and curcumin (Cur) on gentamicin (GM)-induced nephrotoxicity in rats. Rats were divided into four groups as follows: group 1 received normal saline and served as normal controls, group 2 received GM only, group 3 concurrently received GM and TQ and group 4 concurrently received GM and Cur. At day 21, rats were sacrificed and samples were collected for assaying serum tumor necrosis factor alpha (TNF-α), urea and creatinine levels, and renal lipid peroxidaion, glutathione (GSH) content as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. In addition, kidneys were collected for histopathological examination and immunohistochemical determination of the antiapoptotic protein, B-cell lymphoma 2 (Bcl-2). The biochemical results showed that GM-induced nephrotoxicity was associated with a significant increase in serum TNF-α, urea and creatinine as well as renal lipid peroxidation. On the other hand, renal GSH content and GPx and SOD activities were significantly declined. Concomitant administration of either TQ or Cur efficiently alleviated the altered biochemical and histopathological features. In conclusion, both TQ and Cur showed more or less similar marked renoprotective effect against GM-induced nephrotoxicity through their antioxidant, anti-inflammatory and anti-apoptotic efficacies.

Keywords: Bcl-2; apoptosis; curcumin; gentamicin; inflammation; nephrotoxicity; thymoquinone.

Table 1. Effect of TQ and Cur on serum urea and creatinine levels in GM-administered rats

Figure 1. Effect of TQ and Cur on serum TNF-α in GM-administered rats. Data are expressed as Mean ± SE. Means which share the same superscript symbol(s) are not significantly different, P < 0.001.

Figure 2. Effect of TQ and Cur on renal malondialdehyde (MDA) levels in GM-administered rats. Data are expressed as Mean ± SE. Means which share the same superscript symbol(s) are not significantly different, P < 0.001.

Figure 3. Effect of TQ and Cur on renal GSH levels in GM-administered rats. Data are expressed as Mean ± SE. Means which share the same superscript symbol(s) are not significantly different, P < 0.001.

Figure 4. Effect of TQ and Cur on renal GPx activity in GM-administered rats. Data are expressed as Mean ± SE. Means which share the same superscript symbol(s) are not significantly different, P < 0.001.

Figure 5. Effect of TQ and Cur on renal SOD activity in GM-administered rats. Data are expressed as Mean ± SE. Means which share the same superscript symbol(s) are not significantly different, P < 0.001.

Figure 6. Photomicrographs of kidney sections of normal rat showing glomerulus (G), proximal tubules (p) and distal tubules (d). (6a) (X100) and (6b) (X400).

Figure 7. A photomicrograph of H&E stained kidney section of GM-administered rats (Group 2) showing dilated hypermic portal vein (hg), inflammatory cells infiltration (if) (7a), damaged and dilated tubule (t) with if (7b), complete atrophy of some glomeruli (arrow), desquamation of tubular epithelium with cytoplasmic vaculations (v) (7c), odema (o) with a number of inflammatory cells, proximal tubular necrosis (arrow) (7d), and interstitial haemorrhage (arrow) accompanied with proximal tubular necrosis and shrinkage of glomerular capillary (7e and f), (X400)

Figure 8. (8a) Kidney section of group 3 (GM + TQ) showing nearly normal renal tubules (t) and renal corpuscles (g), (8b) kidney section of group 4 (GM + Cur) showing normal renal corpuscles (g), normal renal tubules (t) with interstitial haemorrhage (arrow), (H&E, X400)

Figure 9. Representative Bcl-2 immunohistochemistry of kidney sections of N (9a), GM (9b), GM + TQ (9c) and GM + Cur (9d)