Ketamine delays progression of oxidative and damaged cataract through regulating HMGB-1/NF-κB in lens epithelial cells

Abstract

Objective: Lens epithelial cell (LEC) membrane damage is one of the pathogenesis of cataract. High mobility group box-1 (HMGB-1) and nuclear factor-κB (NF-κB) play vital roles in a variety of diseases, such as inflammation. Ketamine has numerous pharmacological effects that can inhibit inflammation. However, its role in cataract rats LECs has not yet been elucidated.

Materials and methods: LECs were isolated from SD rats and cultured in vitro. The cells were randomly divided into three groups, including the control group, cataract model group induced by H₂O₂, and ketamine group treated by 10 mM ketamine under H₂O₂ environment. LECs proliferation was assessed by MTT assay. LECs apoptosis was evaluated by Caspase-3 activity detection. NF-κB mRNA and protein expressions were tested by real-time PCR and Western blot. HMGB-1 expressions in cells and supernatant were detected by real-time PCR and ELISA. TNF-α and IL-1β secretions were detected by ELISA.

Results: In H₂O₂ model group, the LECs proliferation was significantly inhibited, the caspase-3 activity significantly increased, HMGB-1 mRNA and secretion significantly enhanced, NF-κB mRNA and protein levels significantly elevated, compared to the Control group (p < .05). While the TNF-α and IL-1β secretions significantly up-regulated in H₂O₂ model group compared to the Control group (p < .05). Ketamine significantly promoted the LECs proliferation, significantly reduced the caspase-3 activity, and significantly declined the HMGB expression compared to H₂O₂ model group (p < .05). The NF-κB mRNA and protein levels were significantly decreased, TNF-α and IL-1β secretions were significantly decreased in the Ketamine group compared with the model group (p < .05).

Conclusions: Ketamine delays the progression of oxidative and damaged cataract by regulating HMGB-1/NF-κB expression, inhibiting TNF-α, IL-1β, and apoptosis, and promoting cell proliferation.

Keywords:

• Ketamine
• HMGB1
• NF-κB
• cataract
• lens epithelial cells

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Zhejiang Science and Technology Program of Traditional Chinese Medicine [No. 2017ZQ014].