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<p>D-galactose (D-Gal) is used to induce aging-associated pathological complications; however, its dose-dependent effects on RAGE-NF-κB and Nrf2 pathways remain unexplored. We examine the effects of D-Gal (400, 500, and 600&#xa0;mg/kg body weight) on glycation, inflammation, and detoxification parameters in the liver and kidney tissues of Wistar rats. Rats received subcutaneous D-Gal injections for 56&#xa0;days, while the control rats received 0.9% saline. Blood samples were collected at 15-day intervals, and renal function was assessed using 24-h urine samples. After treatment, rats were sacrificed, liver and kidney tissues were harvested. D-Gal administration altered liver and kidney function by a dose-dependent increase in creatinine excretion upto 1.3-fold. Histological analysis revealed glomerular hypertrophy and hepatocellular injury. Additionally, an increase in GFR by 1.8-fold was observed (p &lt; 0.05). D-Gal treatment showed a time-dependent increase in fructosamine (day 15), protein carbonyl content (day 30), and advanced glycation end products (AGEs) by day 56, accompanied by reduced free amino and thiol groups. Similar trends were observed in tissues, with D-Gal 500 showing the most pronounced effects (p &lt; 0.001). Antioxidant and detoxification parameters exhibited time-dependent alterations, with changes in GSH levels and catalase activity in tissues (p &lt; 0.001). D-Gal treatment significantly modulated RAGE and NF-κB expression at the gene and protein levels. D-Gal 600 induced a 7.5-fold increase in RAGE expression (p &lt; 0.0001). NF-κB and Nrf2 expression were concentration-dependent, with changes at the protein level. Overall, D-Gal 500 exerted maximal effects via the RAGE-NF-κB-Nrf2 axis without significant cellular damage.</p>

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Modulation of glycation, inflammation, and detoxification pathways by D-Galactose through the RAGE–NF-κB–Nrf2 signaling axis in liver and kidney of Wistar rats

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  • 出版模式：

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  • 发表日期：

    2026年8月2日

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  • Nilima S. Bangar,
  • Baishali Chakraborty,
  • Rashmi S. Tupe

摘要

D-galactose (D-Gal) is used to induce aging-associated pathological complications; however, its dose-dependent effects on RAGE-NF-κB and Nrf2 pathways remain unexplored. We examine the effects of D-Gal (400, 500, and 600 mg/kg body weight) on glycation, inflammation, and detoxification parameters in the liver and kidney tissues of Wistar rats. Rats received subcutaneous D-Gal injections for 56 days, while the control rats received 0.9% saline. Blood samples were collected at 15-day intervals, and renal function was assessed using 24-h urine samples. After treatment, rats were sacrificed, liver and kidney tissues were harvested. D-Gal administration altered liver and kidney function by a dose-dependent increase in creatinine excretion upto 1.3-fold. Histological analysis revealed glomerular hypertrophy and hepatocellular injury. Additionally, an increase in GFR by 1.8-fold was observed (p < 0.05). D-Gal treatment showed a time-dependent increase in fructosamine (day 15), protein carbonyl content (day 30), and advanced glycation end products (AGEs) by day 56, accompanied by reduced free amino and thiol groups. Similar trends were observed in tissues, with D-Gal 500 showing the most pronounced effects (p < 0.001). Antioxidant and detoxification parameters exhibited time-dependent alterations, with changes in GSH levels and catalase activity in tissues (p < 0.001). D-Gal treatment significantly modulated RAGE and NF-κB expression at the gene and protein levels. D-Gal 600 induced a 7.5-fold increase in RAGE expression (p < 0.0001). NF-κB and Nrf2 expression were concentration-dependent, with changes at the protein level. Overall, D-Gal 500 exerted maximal effects via the RAGE-NF-κB-Nrf2 axis without significant cellular damage.