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Vaccinia Virus Complement Control Protein (VCP) Ameliorates Kidney Damage Following Ischemia/Reperfusion Injury In Rats
Author(s) -
Ghebremariam Yohannes T,
Engelbrecht Gert,
Tyler Marilyn,
Lotz Zoe,
Govender Dhirendra,
Kotwal Girish J,
Kahn Del
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1144
Subject(s) - saline , immunohistochemistry , medicine , creatinine , reperfusion injury , kidney , ischemia , pathology , transplantation , h&e stain , pharmacology
Aim: The aim of the study was to evaluate the roles of the natural VCP and the humanized recombinant VCP (hrVCP) in a renal ischemia/reperfusion (I/R) injury model. Methods: Long Evans rats weighing 422–479g were subjected to bilateral I/R injury by clamping both the renal arteries for 60 min followed by 24 h of reperfusion. The animals were randomly allocated to receive VCP, hrVCP, phosphate‐buffered saline (PBS) or sham groups. Blood samples were collected and the kidneys removed for histopathological and immunohistochemical studies. Results: The biochemical studies showed that the PBS group displayed 2.7‐fold and 10‐fold increases in the serum urea and creatinine concentrations respectively compared to the VCP/hrVCP groups. Moreover, the histopathological study revealed severe tubular damage and aggregation of neutrophils in the PBS group compared to the focal tubular injury in the VCP and hrVCP treated animals. The immunohistochemical study displayed marked deposition of C3 in the renal tubules of the PBS group compared to the focal C3 staining in the VCP/hrVCP groups. Conclusion: The vaccinia virus complement control proteins ameliorated renal I/R injury possibly by inhibiting the local biosynthesis of the C3 complement component. Source of Funding: The research was supported by the Wellcome Trust UK (GJK) and the Poliomyelitis Research Foundation & the University of Cape Town (YTG).