Metformin attenuated histopathological ocular deteriorations in a streptozotocin-induced hyperglycemic rat model

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2021-03, Vol.394 (3), p.457-467
• Main Authors: Nahar, Nazmun, Mohamed, Suhaila, Mustapha, Noordin Mohamed, Lau, SengFong, Ishak, Nur Iliyani Mohd, Umran, Norshahira Solehah
• Format: Article
• Language: English
• Subjects: Animals; Antidiabetics; Biomedical and Life Sciences; Biomedicine; Blood glucose; Body weight; Claudin-1 - blood; Conjunctiva; Cornea; Diabetes; Diabetes Complications - blood; Diabetes Complications - drug therapy; Diabetes Complications - pathology; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - pathology; Diabetic retinopathy; Eye Diseases - blood; Eye Diseases - drug therapy; Eye Diseases - etiology; Eye Diseases - pathology; Eye disorders; Fasting; Glucose; Glutathione; Glutathione - blood; Hyperglycemia; Hyperglycemia - blood; Hyperglycemia - chemically induced; Hyperglycemia - drug therapy; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Inflammation; Iris; Male; Malondialdehyde; Malondialdehyde - blood; Metformin; Metformin - pharmacology; Metformin - therapeutic use; Neurosciences; Optic nerve; Original Article; Oxidative stress; Pharmacology/Toxicology; Rats; Rats, Sprague-Dawley; Retina; Retinopathy; Rodents; Streptozocin; Tumor Necrosis Factor-alpha - blood; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - blood; Vascularization
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-020-01989-w

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.