Vitamin D3 alleviates corticosteroid-mediated gastric damage in rats: targeting HMGB1/inflammation/apoptosis pathway, gastric angiogenesis and proliferation

Long-term use of synthetic corticosteroids has a gastric damaging effect. This research examined the gastro-protective action of Vitamin D3 ‎against corticosteroid-induced gastric injury in rats. Forty male adults Wistar albino rats were allocated into control, Vitamin D3‎, prednisolone-induced gastric injury (PIGI) and Vitamin D3‎ + PIGI groups. Total acidity and mucous content, as well as prostaglandin E2 (PGE2), high mobility group box 1 (HMGB1), malondialdehyde (MDA), superoxide dismutase (SOD) activity, catalase and inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10)] were measured in stomach tissues. Also, gastric tissues were histopathologically examined and evaluated for collagen, gastric B cell lymphoma-2 protein (Bcl-2), endothelial nitric oxide synthase (e-NOS) and proliferating cell nuclear antigen (PCNA) expression. Vitamin D3 reduced stomach acidity and increased gastric mucous secretion and gastric PGE2. It significantly decreased gastric HMGB1, MDA, TNF-α and IL-1β, while increased gastric SOD activity, catalase and IL-10. Moreover, Vitamin D3 mitigated the stomach histopathological abnormalities of corticosteroids. The expressions of Bcl-2, e-NOS and PCNA in stomach were apparently upregulated. Vitamin D3‎ co-administration could protect against the gastric injurious effect of corticosteroids. Vitamin D3 attenuated gastric inflammation and apoptosis through downregulation of HMGB1, while also improving gastric angiogenesis and proliferation.