Abstract
DL-3-n-butylphthalide (NBP) is a therapeutic drug used for ischemic stroke treatment. Here, we investigated the impact of NBP on the development of rat diabetic cataract induced by intraperitoneal injection of streptozotocin (STZ). NBP was then administrated by oral gavage for nine weeks. Cataract development was monitored through ophthalmoscope inspections. The levels of blood glucose and serum reactive oxygen species (ROS), malondialdehyde (MDA) and 8-Hydroxydeovexyguanosine (8-OHdG) were measured. Total and soluble protein and oxidative stress parameters, such as 2, 4- dinitrophenylhydrazone (DNP), 4-hydroxynonenal (4-HNE) and MDA in the lenses were determined by Western blot and thiobarbituric acid analyses. The expressions of NF-E2-related factor 2 (Nrf2) and its downstream antioxidant enzymes, thioredoxin (TRX), Catalase and nuclear accumulation of Nrf2 were determined by Western blot and immunohistochemistry analyses. We showed that NBP treatment significantly improved the cataract scores, the levels of DNP, 4-HNE, and MDA in the lens compared to the non-treated groups. NBP also enhanced the expressions of Nrf2, TRX and catalase in the lens of diabetic rats. In addition, NBP treatment also decreased levels of blood glucose, serum MDA and 8-OHdG. These results suggested that NBP treatment significantly delayed the onset and progression of diabetic cataract by inhibiting the oxidative stresses.
Highlights
Cataract is characterized by cloudiness and opacification of the eye’s natural lens
We have previously showed that NBP upregulated the expressions of Nrf[2] and its downstream antioxidants enzyme, heme oxygenase-1 (HO-1) in a mouse model of amyotrophic lateral sclerosis[14]
We demonstrated that NBP administration effectively inhibited the development and progress of STZ-induced diabetic cataract by morphological observations, histological examinations, and biochemical analyses
Summary
NBP increased body weight and reduced the blood glucose level in diabetic rats. No rats in the control group died and no statistical mortality was observed in the DM (2 of 15) and DM + NBP (3 of 15) groups during the experiment. Following treatment with NBP, the concentrations of MDA and 8-OHdG were significantly reduced compared to that of non-treated diabetic rats at nine weeks (p < 0.001; p < 0.01, respectively). A robust increase of 4-HNE levels in the lens was observed in DM rats by 242% compared with the control animals (p < 0.001); and NBP treatment significantly attenuated the elevation of 4-HNE levels in diabetic rats by 40% (p < 0.001, Fig. 3b). The increased Nrf[2] expression was observed in the NBP-treated DM group, especially in lens epithelial cells. In concordance with Nrf[2], the expression of TRX and Catalase were significantly decreased in the DM group while remarkably increased 4 folds (TRX, Fig. 4d) and 2.5 folds (Catalase, Fig. 4e) respectively following NBP treatment
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