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.
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This work was supported by the Universiti Putra Research Grant (grant number 9578200).
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Nazmun Nahar (executed the experiments, planning, data collection, and manuscript preparation), Seng Fong Lau and Noordin Mohamed Mustapha (attending veterinary clinicians for animal studies), and Suhaila Mohamed (grant recipient, main supervisor, project planning coordinator and manuscript writing/editing, and principal researcher). Shahira Solehah Umran and Nur Iliyani Mohd Ishak assisted in the animal study. All researchers approved the final manuscript. The authors declare that all data were generated in-house and no paper mill was used.
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Nahar, N., Mohamed, S., Mustapha, N.M. et al. Metformin attenuated histopathological ocular deteriorations in a streptozotocin-induced hyperglycemic rat model. Naunyn-Schmiedeberg's Arch Pharmacol 394, 457–467 (2021). https://doi.org/10.1007/s00210-020-01989-w
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DOI: https://doi.org/10.1007/s00210-020-01989-w