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Alterations in peripheral purinergic and muscarinic signaling of rat bladder after long-term fructose-induced metabolic syndrome

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An Editorial Expression of Concern to this article was published on 23 March 2024

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Abstract

Purpose

We explored the pathophysiologic mechanisms of long-term fructose-induced lower urinary tract symptoms (LUTS) in rats.

Methods

Male Wistar rats were fed with fructose for 3 or 6 months. Biochemical and transcystometric parameters were compared between fructose-fed and age-matched normal-diet rats. Pelvic nerve and external urethral sphincter-electromyogram activity recordings were performed to investigate fructose effects on neural control of bladders. Mitochondrial structure, ATP and acetylcholine content and purinergic and muscarinic cholinergic receptors were examined. Cytosolic cytochrome C staining by Western blot and immunocytochemistry for mitochondrial injury and PGP 9.5 stain for nerve density were also determined.

Results

The fructose-fed rats with higher plasma triglyceride, LDL and fasting glucose levels displayed LUTS with increased frequency and suppressed voiding contractile amplitude in phase 1 and phase 2 duration versus normal-diet control. Fructose feeding altered the firing types in pelvic afferent and efferent nerves and external urethral sphincter-electromyogram activity. Increased mast cell number, disrupted and swollen mitochondria, increased cytosolic cytochrome C stain and expression and decreased nerve density in bladder smooth muscle layers appeared in the fructose-fed rats. Fructose feeding also significantly reduced ATP and acetylcholine content and enhanced protein expression of postsynaptic P2X1, P2X2 and P2X3 purinergic receptors and M2 and M3 muscarinic cholinergic receptors expression in the smooth muscles of urinary bladder.

Conclusion

Long-term fructose feeding induced neuropathy and myopathy in the urinary bladders. Impaired mitochondrial integrity, reduced nerve density, ATP and acetylcholine content and upregulation of purinergic and muscarinic cholinergic receptors expression may contribute to the bladder dysfunction of fructose-fed animals.

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Acknowledgments

This work was supported by the National Science Council of the Republic of China (NSC99-2314-B418-002-MY3 and NSC99-2628-B-002-058-MY3) and research fund from Far-Eastern Memorial Hospital (FEMH-99-D-006).

Conflict of interest

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Authors and Affiliations

  1. Department of Urology, Far-Eastern Memorial Hospital, New Taipei City, Taiwan

    Shiu-Dong Chung

  2. Graduate Institution of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

    Shiu-Dong Chung, Chiang-Ting Chien & Hong-Jeng Yu

  3. Departments of Medical Research, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

    Chiang-Ting Chien

  4. Department of Urology, National Taiwan University Hospital and National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei, Taiwan

    Hong-Jeng Yu

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  1. Shiu-Dong Chung
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  2. Chiang-Ting Chien
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Correspondence to Hong-Jeng Yu.

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Chung, SD., Chien, CT. & Yu, HJ. Alterations in peripheral purinergic and muscarinic signaling of rat bladder after long-term fructose-induced metabolic syndrome. Eur J Nutr 52, 347–359 (2013). https://doi.org/10.1007/s00394-012-0342-4

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  • DOI: https://doi.org/10.1007/s00394-012-0342-4

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