Protective effects of HBSP on ischemia reperfusion and cyclosporine a induced renal injury.

Abstract

Ischemia reperfusion (IR) and cyclosporine A (CsA) injuries are unavoidable in kidney transplantation and are associated with allograft dysfunction. Herein, the effect and mechanism of a novel tissue protective peptide, helix B surface peptide (HBSP) derived from erythropoietin, were investigated in a rat model. The right kidney was subjected to 45 min ischemia, followed by left nephrectomy and 2-week reperfusion, with or without daily treatment of CsA 25 mg/kg and/or HBSP 8 nmol/kg. Blood urea nitrogen was increased by CsA but decreased by HBSP at 1 week and 2 weeks, while the same changes were revealed in urinary protein/creatinine only at 2 weeks. HBSP also significantly ameliorated tubulointerstitial damage and interstitial fibrosis, which were gradually increased by IR and CsA. In addition, apoptotic cells, infiltrated inflammatory cells, and active caspase-3+ cells were greatly reduced by HBSP in the both IR and IR + CsA groups. The 17 kD active caspase-3 protein was decreased by HBSP in the IR and IR + CsA kidneys, with decreased mRNA only in the IR + CsA kidneys. Taken together, it has been demonstrated, for the first time, that HBSP effectively improved renal function and tissue damage caused by IR and/or CsA, which might be through reducing caspase-3 activation and synthesis, apoptosis, and inflammation.

• Authors: Yuanyuan Wu, Junlin Zhang, Feng Liu, Cheng Yang, Yufang Zhang, Aifen Liu, Lan Shi, Yajun Wu, Tongyu Zhu, Michael L Nicholson, Yaping Fan, Bin Yang
• Journal: Clinical & developmental immunology (Clin Dev Immunol) Vol. 2013 Pg. 758159 ( 2013) ISSN: 1740-2530 [Electronic] Egypt
• PMID: 24282430 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptide Fragments
• Protective Agents
• RNA, Messenger
• glutaminyl-glutamyl-glutaminyl-leucyl-glutamyl-arginyl-alanyl-leucyl-asparagyl-seryl-serine
• Erythropoietin
• Cyclosporine
• Caspase 3

Topics

• Acute Kidney Injury (etiology, pathology, physiopathology, prevention & control)
• Animals
• Apoptosis
• Caspase 3 (genetics, metabolism)
• Cyclosporine (adverse effects)
• Enzyme Activation
• Erythropoietin (therapeutic use)
• Fibrosis
• Gene Expression
• Inflammation (pathology)
• Kidney (pathology, physiopathology)
• Kidney Function Tests
• Male
• Peptide Fragments (therapeutic use)
• Protective Agents (therapeutic use)
• RNA, Messenger (genetics, metabolism)
• Rats
• Reperfusion Injury (complications)