Lactucaxanthin protects retinal pigment epithelium from hyperglycemia-regulated hypoxia/ER stress/VEGF pathway mediated angiogenesis in ARPE-19 cell and rat model.

Anitha, Rani Elavarasan and Janani, Rajasekar and Divya, P. and Baskaran, V. (2021) Lactucaxanthin protects retinal pigment epithelium from hyperglycemia-regulated hypoxia/ER stress/VEGF pathway mediated angiogenesis in ARPE-19 cell and rat model. European Journal of Pharmacology, 899. p. 174014.

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Abstract

Hyperglycemia mediated perturbations in biochemical pathways induce angiogenesis in diabetic retinopathy (DR) pathogenesis. The present study aimed to investigate the protective effects of lactucaxanthin, a predominant lettuce carotenoid, on hyperglycemia-mediated activation of angiogenesis in vitro and in vivo diabetic model. ARPE-19 cells cultured in 30 mM glucose concentration were treated with lactucaxanthin (5 μM and 10 μM) for 48 h. They were assessed for antioxidant enzyme activity, mitochondrial membrane potential, reactive oxygen species, and cell migration. In the animal experiment, streptozotocin-induced diabetic male Wistar rats were gavaged with lactucaxanthin (200 μM) for 8 weeks. Parameters like animal weight gain, feed intake, water intake, urine output, and fasting blood glucose level were monitored. In both models, lutein-treated groups were considered as a positive control. Hyperglycemia-mediated angiogenic marker expressions in ARPE-19 and retina of diabetic rats were quantified through the western blot technique. Expression of hypoxia, endoplasmic reticulum stress markers, and vascular endothelial growth factor were found to be augmented in the hyperglycemia group compared to control (P < 0.05). Hyperglycemia plays a crucial role in increasing cellular migration and reactive oxygen species besides disrupting tight junction protein. Compared to lutein, lactucaxanthin aids retinal pigment epithelium (RPE) function from hyperglycemia-induced stress conditions via downregulating angiogenesis markers expression. Lactucaxanthin potentiality observed in protecting tight junction protein expression via modulating reactive oxygen species found to conserve RPE integrity. Results demonstrate that lactucaxanthin exhibits robust anti-angiogenic activity for the first time and, therefore, would be useful as an alternative therapy to prevent or delay DR progression.

Item Type:	Article
Uncontrolled Keywords:	Angiogenesis Diabetic retinopathy Endoplasmic reticulum stress Hypoxia Lactucaxanthin Vascular endothelial growth factor
Subjects:	500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 14 Carotenoid Chemistry 600 Technology > 01 Medical sciences > 04 Diabetes Mellitus
Divisions:	Dept. of Biochemistry
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	23 Nov 2021 09:37
Last Modified:	23 Nov 2021 09:37
URI:	http://ir.cftri.res.in/id/eprint/15068

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