Sunitinib's Effect on Bilateral Optic Nerve Damage in Rats Following the Unilateral Clamping and Unclamping of the Common Carotid Artery

Abstract

Background/objectives: Common carotid artery occlusion can cause oxidant and inflammatory damage to the optic nerve. In this study, the effect of sunitinib was investigated, the antioxidant and anti-inflammatory properties of which have been previously reported and shown to be protective in I/R injury and in preventing bilateral optic nerve ischemia-reperfusion (I/R) injuries after unilateral common carotid artery ligation in rats. Methods: In this study, 18 Albino Wistar male rats were divided into SG (sham-operated), CCU (clamping and unclamping), and SCCU (sunitinib + clamping and unclamping) groups. One hour before the surgical procedures, sunitinib (25 mg/kg, oral) was given to SCCU rats. Anesthesia was induced with ketamine (60 mg/kg, ip) and sevoflurane. The right common carotid arteries of all rats were accessed under anesthesia. While the skin opened in SG rats was closed with sutures, the right common carotid arteries of CCU and SCCU rats were clipped, and an ischemia period was created for 10 min. Then, reperfusion (6 h) was achieved by unclipping. After euthanasia with ketamine (120 mg/kg, intraperitoneally), the right and left optic nerves of the rats were removed and examined biochemically and histopathologically. Results: Malondialdehyde, tumor necrosis factor α, interleukin-1β, and interleukin-6 were increased, and total glutathione levels had decreased in both ipsilateral and contralateral optic nerves (p < 0.05). These changes were more prominent on the ipsilateral side. Similarly, histopathological damage was observed to be more on the ipsilateral side (p < 0.05). Biochemical and histopathological changes were significantly suppressed in rats receiving sunitinib treatment (p < 0.05). Conclusions: Sunitinib may protect optic nerve tissue against I/R injury by reducing oxidative stress and inflammation.

Keywords: inflammation; ischemia–reperfusion; optic nerve; oxidative stress; sunitinib.

Figure 1

Right and left optic nerve MDA levels in the experimental groups. The bars show the mean ± standard deviation, n = 6. *, p < 0.001 vs. SG (right optic nerve); **, p < 0.001 vs. CCU (right optic nerve); ^†, p < 0.001 vs. SG (left optic nerve); ^‡, p < 0.05 vs. CCU (left optic nerve). MDA, malondialdehyde; SG, sham-operated group; CCU, right common carotid clamping and unclamping operated group; SCCU, sunitinib + common carotid clamping and unclamping operated group.

Figure 2

Right and left optic nerve tGSH levels in experimental groups. Bars show mean ± standard deviation, n = 6. *, p < 0.001 vs. SG (right optic nerve); **, p < 0.001 vs. CCU (right optic nerve); ^†, p < 0.001 vs. SG (left optic nerve); ^‡, p < 0.001 vs. CCU (left optic nerve). tGSH, total glutathione; SG, sham-operated group; CCU, right common carotid clamping and unclamping operated group; SCCU, sunitinib + common carotid clamping and unclamping operated group.

Figure 3

Right and left optic nerve TNF-α levels in experimental groups. Bars show mean ± standard deviation, n = 6. *, p < 0.001 vs. SG (right optic nerve); **, p < 0.001 vs. CCU (right optic nerve); ^†, p < 0.001 vs. SG (left optic nerve); ^‡, p < 0.001 vs. CCU (left optic nerve). TNF-α, tumor necrosis factor α; SG, sham-operated group; CCU, right common carotid clamping and unclamping operated group; SCCU, sunitinib + common carotid clamping and unclamping operated group.

Figure 4

Right and left optic nerve IL-1β levels in experimental groups. Bars show mean ± standard deviation, n = 6. *, p < 0.001 vs. SG (right optic nerve); **, p < 0.001 vs. CCU (right optic nerve); ^†, p < 0.001 vs. SG (left optic nerve); ^‡, p < 0.001 vs. CCU (left optic nerve). IL-1β, interleukin-1β; SG, sham-operated group; CCU, right common carotid clamping and unclamping operated group; SCCU, sunitinib + common carotid clamping and unclamping operated group.

Figure 5

Right and left optic nerve IL-6 levels in experimental groups. Bars show mean ± standard deviation, n = 6. *, p < 0.001 vs. SG (right optic nerve); **, p < 0.001 vs. CCU (right optic nerve); ^†, p < 0.05 vs. SG (left optic nerve); ^‡, p < 0.05 vs. CCU (Left optic nerve). IL-6; interleukin-6; SG, sham-operated group; CCU, right common carotid clamping and unclamping operated group; SCCU, sunitinib + common carotid clamping and unclamping operated group.

Figure 6

(A–C) Histopathological appearances of the right optic nerves of the experimental groups (H&E ×400). (A) SG group: ➔, astrocyte; ★, capillary vessel view. (B) CCU group: ➔, hypertrophied and degenerated astrocyte; ★, vascular dilatation and congestion; ∗, vacuolization; ➲, inflammatory cell; e, edema; curved arrow, increase in thickness. (C) SCCU group: →, hypertrophic and degenerated astrocyte; ★, mild vascular congestion and dilatation; ∗, vacuolization; e, edema. SG, sham-operated group; CCU, right common carotid clamping and unclamping operated group; SCCU, sunitinib + common carotid clamping and unclamping operated group.

Figure 7

(A–C) Histopathological appearances of the left optic nerves of the experimental groups (H&E ×400). (A) SG group: ➔, astrocyte; ★, blood capillary, ×400. (B) CCU group: ➔, hypertrophied and degenerated astrocyte; ★, vascular congestion and dilatation; ∗, vacuolization; e, edema. (C) SCCU group: →, astrocyte; ★, blood capillary. SG, sham-operated group; CCU, right common carotid clamping and unclamping operated group; SCCU, sunitinib + common carotid clamping and unclamping operated group.