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Abstract: SA-PO0418

Exogenous Adrenomedullin Attenuate Zymosan Induced Severe Peritoneal Injury with Complement Activation in Rats

Session Information

Category: Dialysis

  • 802 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

  • Kim, Hangsoo, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan
  • Yokoi, Jumpei, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan
  • Kamegai, Naoki, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan
  • Ototake, Satoshi, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan
  • Fukui, Sosuke, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan
  • Maruyama, Shoichi, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan
  • Kitamura, Kazuo, Miyazaki Daigaku, Miyazaki, Miyazaki Prefecture, Japan
  • Mizuno, Masashi, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan
Background

Fungal/yeast peritonitis in peritoneal dialysis (PD) patients causes severe peritoneal damage and is associated with PD discontinuation and high mortality.
Adrenomedullin (ADM), first discovered as a vasodilating peptide, has been reported to have multiple physiological functions, including anti-inflammatory effects. In the context of PD, the presence of ADM has been documented in the peritoneal effluent and mesothelial cells. Although ADM may protect the peritoneum, its role in the peritoneal cavity remains to be elucidated.
In the present study, we investigated whether the administration of ADM offers protective benefits to peritoneal injuries in a rat model of fungal/yeast peritonitis.

Methods

A model of fungal/yeast peritonitis was induced in Sprague Dawley rats through the injection of methylglyoxal (MGO), followed by zymosan (MGO/Zy peritonitis). The administration of human ADM (ADM group) or vehicle (control group) was performed intraperitoneally on the rats. Macroscopic and microscopic findings of peritoneal injury in the rats were compared within the groups.

Results

The Macroscopic score, which includes gastrointestinal adhesions, was lower in the ADM group than in the control group. A microscopic examination revealed that the ADM group had reduced peritoneal thickness, decreased infiltration of inflammatory cells, and reduced complement deposition. The administration of ADM with ADM (22-52), an antagonist for the ADM receptor, did not fully reverse the effects on peritoneal injury in MGO/Zy peritonitis. The findings suggested that the impact of ADM was not exclusively attributable to the ADM signal transmitted through the ADM receptor; it was also associated with other functions. Subsequently, the focus shifts to complement, as ADM binds with complement factor H. To evaluate the role of ADM in the complement system, The C5b-9 levels were quantified using an ELISA assay after zymosan was incubated in rat serum in the presence of ADM. The assay demonstrated that C5b-9 levels were reduced by the addition of ADM.

Conclusion

We demonstrated the therapeutic potential of exogenous administration of ADM to inhibit peritoneal injury in fungal/yeast peritonitis through its anti-inflammatory effects, including complement modulatory properties.

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)