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Background <p>Lithium is extensively used for mood stabilization in bipolar disorder, but its long-term use can lead to nephrotoxicity, characterized by a reduction in glomerular filtration rate (GFR) and potential progression to end-stage renal disease (ESRD). Exercise has been shown to have protective effects on renal function, yet the impact of varying exercise intensities on lithium-induced nephropathy is not well understood.</p> Aim <p>This study aimed to investigate the effects of different intensities of endurance training on kidney function and inflammation in a rat model of lithium-induced nephropathy, focusing on the expression of aquaporin 2 (AQP2), glycogen synthase kinase 3-beta (GSK-3β), and SIRT1.</p> Methods <p>Thirty-five male Wistar rats were divided into five groups: control, lithium-only, lithium with low-intensity exercise (LIT), lithium with medium-intensity exercise (MIT), and lithium with high-intensity exercise (HIT). The lithium-induced nephropathy model was established by administering lithium in food. Exercise groups underwent treadmill training at specified intensities for eight weeks. Fractional excretion of sodium (FENa) was measured, and GFR was evaluated by Cr clearance. ELISA and Western blotting assessed inflammatory markers (TNF-α, IL-10), SIRT1, GSK-3β, and AQP2 expressions in kidney tissues.</p> Results <p>Lithium significantly reduced Cr clearance and increased FENa compared to controls. All exercise intensities improved Cr clearance and reduced FENa, with HIT showing the most significant improvement. Exercise at all intensities reduced TNF-α levels and increased IL-10 levels, with MIT and HIT significantly enhancing SIRT1 levels. Lithium reduced the expression of GSK-3β and AQP2, whereas exercise increased their expression across all intensities.</p> Conclusion <p>Endurance training, particularly at high intensity, significantly mitigates lithium-induced renal impairment by improving GFR, reducing inflammation, and enhancing the expression of renal protective proteins. These findings suggest that tailored exercise regimens could be beneficial for patients undergoing long-term lithium therapy to prevent renal damage.</p> Clinical trial number <p>Not applicable.</p> Graphical Abstract <p></p>

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Various endurance training intensities improve GFR and Up-regulate AQP2/GSK3β in lithium-induced nephropathic rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月6日

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  • Shadan Saberi,
  • Mohammad Amin Rajizadeh,
  • Mohammad Khaksari,
  • Azadeh Saber,
  • Mohammad Akhbari,
  • Soheil Aminizadeh,
  • Forouzan Rafie

摘要

Background

Lithium is extensively used for mood stabilization in bipolar disorder, but its long-term use can lead to nephrotoxicity, characterized by a reduction in glomerular filtration rate (GFR) and potential progression to end-stage renal disease (ESRD). Exercise has been shown to have protective effects on renal function, yet the impact of varying exercise intensities on lithium-induced nephropathy is not well understood.

Aim

This study aimed to investigate the effects of different intensities of endurance training on kidney function and inflammation in a rat model of lithium-induced nephropathy, focusing on the expression of aquaporin 2 (AQP2), glycogen synthase kinase 3-beta (GSK-3β), and SIRT1.

Methods

Thirty-five male Wistar rats were divided into five groups: control, lithium-only, lithium with low-intensity exercise (LIT), lithium with medium-intensity exercise (MIT), and lithium with high-intensity exercise (HIT). The lithium-induced nephropathy model was established by administering lithium in food. Exercise groups underwent treadmill training at specified intensities for eight weeks. Fractional excretion of sodium (FENa) was measured, and GFR was evaluated by Cr clearance. ELISA and Western blotting assessed inflammatory markers (TNF-α, IL-10), SIRT1, GSK-3β, and AQP2 expressions in kidney tissues.

Results

Lithium significantly reduced Cr clearance and increased FENa compared to controls. All exercise intensities improved Cr clearance and reduced FENa, with HIT showing the most significant improvement. Exercise at all intensities reduced TNF-α levels and increased IL-10 levels, with MIT and HIT significantly enhancing SIRT1 levels. Lithium reduced the expression of GSK-3β and AQP2, whereas exercise increased their expression across all intensities.

Conclusion

Endurance training, particularly at high intensity, significantly mitigates lithium-induced renal impairment by improving GFR, reducing inflammation, and enhancing the expression of renal protective proteins. These findings suggest that tailored exercise regimens could be beneficial for patients undergoing long-term lithium therapy to prevent renal damage.

Clinical trial number

Not applicable.

Graphical Abstract