Metformin attenuated histopathological ocular deteriorations in a streptozotocin-induced hyperglycemic rat model
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ORIGINAL ARTICLE
Metformin attenuated histopathological ocular deteriorations in a streptozotocin-induced hyperglycemic rat model Nazmun Nahar 1 & Suhaila Mohamed 1 Norshahira Solehah Umran 1
&
Noordin Mohamed Mustapha 2 & SengFong Lau 2 & Nur Iliyani Mohd Ishak 1 &
Received: 22 June 2020 / Accepted: 6 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Diabetes mellitus (DM) often causes ocular disorders leading to vision loss. Metformin is commonly prescribed for type 2 diabetes. This study assessed the effect of metformin on hyperglycemic histopathological eye abnormalities and some possible pathways involved. Male rats were divided into 3 groups (N = 6), namely, healthy control, hyperglycemic non-treated control, and hyperglycemic rats treated with 200 mg/kg metformin. Two weeks after diabetes induction by an intraperitoneal streptozotocin (60 mg streptozotocin (STZ)/kg) injection, the rats develop ocular abnormalities, and metformin (200 mg/kg) treatment was administered daily. Rats underwent dilated retinal digital ophthalmoscope examination and graded for diabetic retinopathy. Rats were sacrificed at 12 weeks, and the cornea, lens, sclera, ciliary body, iris, conjunctiva, retinal, and optic nerve were examined histologically. Rats’ fasting blood glucose and body weight were monitored. Serum tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), claudin-1, and glutathione/malondialdehyde ratios were analyzed. Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-α, VEGF, claudin-1, and glutathione/ malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats. Metformin attenuated hyperglycemia-associated histopathological eye deteriorations, possibly partly by ameliorating vascular leakage, oxidative stress, inflammation, and neovascularization, without affecting the fasting blood glucose levels or body weights in these STZ-induced diabetic rats. Keywords Cornea . Lens . Conjunctiva . Retina . Optic nerve . Claudin-1
Introduction Diabetes mellitus (DM) affects over 240 million people worldwide (International Diabetes Federation 2006; Unwin et al. 2011), and 25% of diabetics have ocular disorders (Webster and Phillips 2014) (retinopathy, glaucoma, cataract, Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00210-020-01989-w) contains supplementary material, which is available to authorized users. * Suhaila Mohamed [email protected]; [email protected] 1
UPM-MAKNA Laboratory of Cancer Research, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
2
Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Malaysia
scotoma, corneal abnormalities, and keratopathy) (CalvoMaroto et al. 2014). Diabetes increases vascular permeability, ocular
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