DL-3-n-butylphthalide delays the onset and progression of diabetic cataract by inhibiting oxidative stress in rat diabetic model

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.

Chrysin Reduces Oxidative Stress but Does Not Affect Polyol Pathway in the Lenses of Type 1 Diabetic Rats

“…We also noted that in the lenses of the DM rats, MDA level was elevated, which may be a result of the oxidant/antioxidant imbalance. Our results overlap with other studies in which an increase in the MDA level was described in the lenses of diabetic animals [48][49][50][51]. ROS and free radicals may also interact directly with the thiol groups of amino acids in peptides and proteins, which promotes oxidation of these compounds and their structure and/or function change, and may lead to protein aggregation [52].…”

Nrf2 as a target for prevention of age‐related and diabetic cataracts by against oxidative stress

“…NBP‐treated mice were also shown improvement in oxidative stress, as indicated by the levels of DNP, 4‐HNE, and MDA in lens. Even though the precise mechanisms of NBP in preventing diabetic cataract are still needed to investigate, NBP might be a promising therapeutic drug to prevent or treat diabetic cataract (Wang et al ., ).…”

Potential Protective and Therapeutic Roles of the Nrf2 Pathway in Ocular Diseases: An Update

“…Puerarin [88], Rosa laevigata Michx. extract [89], hyperoside [90], acetyl-Lcarnitine [91], morin [92], trimetazidine [93], rosmarinic acid [94], and DL-3-n-butylphthalide [95] have been shown to protect LECs from OS by activating the Nrf2 pathways. Besides, the inhibition of miRNA-4532 protected human LECs from UV-induced oxidative injury via activating SIRT6-Nrf2 signaling [96].…”

“…Corneal fibroblasts Inhibits TGF-β-induced ROS accumulation and myofibroblast differentiation via enhanced Nrf2-ARE signaling [195] DL-3-n-butylphthalide (NBP) Rat diabetic cataract model Delays the onset and progression of diabetic cataract by enhancing the expressions of Nrf2, TRX, and CAT [95] Acetyl-L-carnitine LECs Prevents homocysteine-induced suppression of Nrf2/Keap1-mediated antioxidation [91] Puerarin Rat diabetic cataract model Prevents cataract development and progression in diabetic rats through Nrf2/HO-1 signaling [88] RPEs Activates Nrf2/HO-1 antioxidant signaling pathway [196] Rosmarinic acid Sprague-Dawley rat pup selenite-induced cataractogenesis model Increases the protein expressions of filensin, calpain 2, Nrf2, SOD, HO-1, and NQO1; the antioxidant enzyme activities; and the GSH level [94] Morin LECs Induces HO-1 via the ERK-Nrf2 signaling pathway [92] Calcium dobesilate…”