Histological and histochemical study of oxidative stress effects on pancreatic tissue in diabetic rats and the protective role of Nigella sativa extract

Abstract

Diabetes mellitus (DM) is a chronic metabolic disease characterized by severe hyperglycemia resulting from defects in insulin secretion or action, with oxidative stress driving its pathogenesis via pancreatic beta-cell destruction. This study investigated histopathological and histochemical alterations in the pancreatic tissue of streptozotocin-induced diabetic rats and evaluated the cytoprotective efficacy of a Nigella sativa (black seed) aqueous extract. Forty adult male Wistar albino rats (200–250 g) were randomly assigned to four groups (n = 10 each): Group I (Normal Control), Group II (Diabetic Control; induced with a single i.p. injection of streptozotocin, 60 mg/kg), Group III (diabetic rats treated orally with 400 mg/kg/day of Nigella sativa extract for 8 weeks), and Group IV (normal rats treated with the extract). Pancreatic tissues were processed for Hematoxylin and Eosin (H&E), Periodic Acid-Schiff (PAS), Masson's trichrome, Gomori's aldehyde fuchsin, and immunohistochemical detection of insulin and glucagon, alongside tissue oxidative stress marker quantification (MDA, SOD, CAT, GPx). Streptozotocin-treated rats exhibited severe histopathological alterations (P<0.001), including a 75.0 % reduction in islet density, a 66.6 % decrease in islet cross-sectional area, extensive periinsular and interlobular fibrosis, and severe depletion of both PAS-positive glycoproteins and insulin-immunoreactive beta cells. These structural changes directly correlated with a significant elevation in malondialdehyde (MDA) levels (P<0.001) and a concurrent decline in SOD, CAT, and GPx antioxidant activities (P<0.001). Daily oral administration of Nigella sativa extract in Group III significantly attenuated these microstructural and biochemical abnormalities (P<0.001). The treatment preserved near-normal islet architecture, reduced connective tissue deposition more than twofold, and drove a substantial 2.1-fold recovery in functional insulin expression relative to the untreated diabetic group. These findings demonstrate that chronic oxidative stress induces profound structural and histochemical damage to both the endocrine and exocrine pancreas, whereas Nigella sativa extract exerts a potent cytoprotective effect mediated by its antioxidant, anti-inflammatory, and anti-fibrotic properties, confirming its therapeutic potential as an effective complementary strategy in managing diabetes mellitus and preventing secondary pancreatic complications.