Ascorbic Acid Attenuates Cadmium Nitrate-Induced Cytotoxicity and Insulin Secretion Deficits in Pancreatic Beta Cells (RIN-m5F)
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Abstract
Cadmium exposure contributes to metabolic disorders, such as type 2 diabetes mellitus, by inducing oxidative stress and impairing pancreatic beta cell’s function. This study investigated the cytotoxic mechanisms of cadmium nitrate in beta cells (RIN-m5F) and evaluated the protective efficacy of ascorbic acid. Cadmium nitrate treatment resulted in a dose-dependent reduction in cell viability (significant at ≥ 5 µM). At the half maximal inhibitory concentration (IC50) of 1.7 µM, cadmium significantly elevated intracellular reactive oxygen species (ROS) and upregulated oxidative stress markers (Nox1 and Nox4) and pro-apoptotic genes (Bax and p53), while downregulating Bcl-2 and pre-insulin expression. Pretreatment with 100 µM ascorbic acid effectively mitigated ROS accumulation and reversed these apoptotic and oxidative gene expression profiles. Functionally, cadmium exposure severely compromised glucose-stimulated insulin secretion (GSIS), reducing levels to 1.43 ± 0.21 ng/mL compared to 6.07 ± 0.91 ng/mL in controls, and suppressed the stimulation index to 1.74 ± 0.26. Ascorbic acid pretreatment significantly attenuated these deficits, partially restoring GSIS (3.59 ± 0.54 ng/mL) and improving the SI to 3.95 ± 0.59. These findings provide mechanistic evidence that ascorbic acid protects beta cells against cadmium-induced toxicity by suppressing oxidative stress and pro-apoptosis genes, thereby preserving insulin secretory function.
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References
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