Dose dependent toxicity of streptozotocin inducing diabetic complications in male Sprague Dawley rats with metabolic biochemical histopathological effects

Abstract

Abstract Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, leading to microvascular and macrovascular complications including cardiomyopathy, retinopathy, neuropathy, and nephropathy. This study evaluated the diabetogenic potential and pathological outcomes of two single intraperitoneal doses of streptozotocin (STZ) in male Sprague Dawley rats. Twenty-four rats (200–220 g) were randomly assigned to three groups (n = 8/group): control, STZ 45 mg/kg, and STZ 60 mg/kg. DM was confirmed 72 h post-injection via elevated serum glucose. At the end of the experiment, blood and tissue samples were collected to assess metabolic parameters, lipid profile, liver function, oxidative stress markers, inflammatory cytokines, and histopathological changes. Both doses induced significant hyperglycemia, elevated glycated hemoglobin, and reduced insulin levels. Diabetic rats also showed dyslipidemia, liver dysfunction, increased oxidative stress (↓GSH, ↑MDA), and elevated inflammatory markers (TNF-α, il-6). Histopathological and morphometric analyses confirmed tissue damage and biochemical alterations. Notably, the 60 mg/kg dose produced a more severe and consistent diabetic phenotype, with greater metabolic derangements, oxidative injury, inflammation, and organ pathology compared to the 45 mg/kg dose. These findings suggest that while both doses effectively induce experimental diabetes, 60 mg/kg STZ provides a more robust model for studying DM-associated complications in vital organs.