Anti-inflammatory effect of lycopene on endotoxin-induced uveitis in rats

ABSTRACT Purpose: We evaluated the efficacy of lycopene, a dietary carotenoid and potent antioxidant, against ocular inflammation and oxidative stress in an experimental uveitis model. Methods: Endotoxin-induced uveitis (EIU) was induced in Sprague-Dawley rats by a single subcutaneous injection of 200 μg lipopolysaccharide (LPS). Induction of EIU was preceded by daily intraperitoneal injection of 10 mg/kg lycopene for three consecutive days (Lycopene + LPS group) or equivolume vehicle (Vehicle + LPS group). A positive control group received 1 mg/kg dexamethasone pretreatment (DEX + LPS), and a negative control group received daily vehicle injection but no LPS (Vehicle Control). Twenty-four hours after LPS or final vehicle administration, eyes were enucleated, and aqueous humor was collected for measurement of the number of infiltrating cells, total protein concentration, and levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and oxidative stress markers. Inflammatory response severity was compared among groups clinically and histopathologically. Results: Infiltrating cell number, total protein concentration, and NO, TNF-α, and IL-6 levels were significantly elevated in the aqueous humor of Vehicle + LPS group rats compared to Vehicle Controls. Compared to the Vehicle + LPS group, lycopene pretreatment significantly reduced aqueous humor concentrations of oxidative stress markers, NO (0.29 ± 0.1 μM vs. 0.19 ± 0.1 μM, p=0.003), TNF-α (71.0 ± 22.3 ng/ml vs. 50.1 ± 2.1 ng/ml, p=0.043), and IL-6 (121.6 ± 3.0 pg/ml vs. 111.1 ± 5.6 pg/ml, p=0.008). Inflammatory score was also reduced (2.0 ± 0.0 vs. 0.4 ± 0.5, p=0.001). Lycopene reduced the infiltrating cell count and protein concentration, but differences did not reach significance. Most lycopene effects were equivalent to dexamethasone. Conclusions: Lycopene may aid in the clinical management of uveitis by suppressing inflammation and oxidative stress.

摘要：
研究目的：本研究评估膳食类胡萝卜素、强效抗氧化剂番茄红素（lycopene）对实验性葡萄膜炎模型中眼部炎症与氧化应激的干预效果。
实验方法：通过单次皮下注射200 μg脂多糖（lipopolysaccharide, LPS）于Sprague-Dawley大鼠体内构建内毒素诱导性葡萄膜炎（endotoxin-induced uveitis, EIU）模型。造模前连续3天每日腹腔注射10 mg/kg番茄红素（番茄红素+LPS组），或等体积溶剂（溶剂+LPS组）。阳性对照组预先给予1 mg/kg地塞米松预处理（地塞米松+LPS组），阴性对照组每日注射溶剂但不给予LPS（溶剂对照组）。于LPS给药或末次溶剂给药24小时后摘除眼球，收集房水以检测浸润细胞数、总蛋白浓度，以及一氧化氮（nitric oxide, NO）、肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α）、白细胞介素-6（interleukin-6, IL-6）与氧化应激标志物水平。通过临床与组织病理学方法比较各组炎症反应严重程度。
结果：与溶剂对照组相比，溶剂+LPS组大鼠房水中浸润细胞数、总蛋白浓度及NO、TNF-α、IL-6水平均显著升高。相较于溶剂+LPS组，番茄红素预处理可显著降低房水中氧化应激标志物、NO（0.29±0.1 μM vs. 0.19±0.1 μM，p=0.003）、TNF-α（71.0±22.3 ng/ml vs. 50.1±2.1 ng/ml，p=0.043）与IL-6（121.6±3.0 pg/ml vs. 111.1±5.6 pg/ml，p=0.008）的浓度。炎症评分亦有所降低（2.0±0.0 vs. 0.4±0.5，p=0.001）。番茄红素可降低浸润细胞计数与蛋白浓度，但差异未达到统计学显著性。多数番茄红素的干预效果与地塞米松相当。
结论：番茄红素可通过抑制炎症与氧化应激，为葡萄膜炎的临床管理提供潜在辅助策略。