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Kidney Week

Abstract: SA-PO1202

Suppressing Exocytosis of Mast Cells and Its Therapeutic Efficacy for Peritoneal Fibrosis in Rats with Chronic Kidney Failure

Session Information

  • CKD: Mechanisms - 3
    October 26, 2024 | Location: Exhibit Hall, Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms

Author

  • Kazama, Itsuro, Miyagi Daigaku Kango Gakugun Daigakuin Kangogaku Kenkyuka, Kurokawa-gun, Miyagi, Japan
Background

In addition to their exocytotic release of chemical mediators, mast cells produce fibroblast-activating factors to facilitate the progression of organ fibrosis in chronic inflammatory diseases. The process of exocytosis in mast cells can be monitored electro-physiologically by the changes in the membrane capacitance (Cm).

Methods

Employing the standard patch-clamp whole-cell recording technique in rat peritoneal mast cells, we examined the effects of anti-allergic drugs on the changes in the Cm. Additionally, using rat models with chronic renal failure (CRF) induced by 5/6 nephrectomy, we actually examined the therapeutic efficacy of these drugs for peritoneal fibrosis complicated with CRF.

Results

Among anti-allergic drugs, second-generation antihistamines, such as olopatadine, loratadine and ketotifen, markedly suppressed the increase in the Cm and directly inhibited the exocytotic process, suggesting their potency as mast cell stabilizers. Of note, tranilast, a potent anti-allergic drug, most effectively and strongly suppressed the increase in the Cm. Therefore, using rat models with CRF, we examined the effects of tranilast (200 mg/kg) on the histopathological features of CRF rat peritoneum. In the fibrotic areas of CRF rat peritoneum, mast cells proliferated in situ and increased their activity by producing fibroblast growth factors. Therapeutic intervention with tranilast actually slowed the progression of peritoneal fibrosis.

Conclusion

From these results, the activation of mast cells was considered to be responsible for the progression of peritoneal fibrosis in uremic condition. Additionally, the results suggested the therapeutic potency of mast cell stabilizers in the treatment of peritoneal fibrosis in CRF.