OBJECTIVE: This study investigates the effect of a superoxide dismutase mimetic, MnTMPyP, on pro- and anti-inflammatory cytokines in acute renal ischemia-reperfusion (IR). MATERIALS AND TREATMENT: Male Sprague-Dawley rats underwent bilateral clamping of the renal arteries for 45 min followed by 1, 4, or 24 h of reperfusion. A subset of animals was treated with MnTMPyP (5 mg/kg, i.p.) or saline. Porcine proximal tubular epithelial cells were ATP-depleted for 4 h followed by recovery for 2 h. METHODS: Cytokines were analyzed by ELISA, and ED1(+) macrophages and CD8(+) T lymphocytes by immunohistochemistry. Statistical analysis was performed using ANOVA. RESULTS: MnTMPyP attenuated the IR-mediated increase in serum creatinine and circulating levels of interleukin (IL)-2 following 24 h of reperfusion. Furthermore, treatment attenuated increases in tissue levels of tumor necrosis factor (TNF)-α, IL-2, IL-4, and IL-13. MnTMPyP partially prevented the IR-induced infiltration of ED1(+) macrophages and CD8(+) T lymphocytes in the kidney. ATP depletion-recovery of porcine proximal tubular epithelial cells resulted in decreased IL-6 and IL-10 levels, and MnTMPyP partially restored these cytokines. CONCLUSIONS: These results show that MnTMPyP is partially effective in reducing inflammation associated with renal IR and that reactive oxygen species play a role in modulating both pro- and anti-inflammatory pathways in acute kidney injury.
OBJECTIVE: This study investigates the effect of a superoxide dismutase mimetic, MnTMPyP, on pro- and anti-inflammatory cytokines in acute renal ischemia-reperfusion (IR). MATERIALS AND TREATMENT: Male Sprague-Dawley rats underwent bilateral clamping of the renal arteries for 45 min followed by 1, 4, or 24 h of reperfusion. A subset of animals was treated with MnTMPyP (5 mg/kg, i.p.) or saline. Porcine proximal tubular epithelial cells were ATP-depleted for 4 h followed by recovery for 2 h. METHODS: Cytokines were analyzed by ELISA, and ED1(+) macrophages and CD8(+) T lymphocytes by immunohistochemistry. Statistical analysis was performed using ANOVA. RESULTS: MnTMPyP attenuated the IR-mediated increase in serum creatinine and circulating levels of interleukin (IL)-2 following 24 h of reperfusion. Furthermore, treatment attenuated increases in tissue levels of tumor necrosis factor (TNF)-α, IL-2, IL-4, and IL-13. MnTMPyP partially prevented the IR-induced infiltration of ED1(+) macrophages and CD8(+) T lymphocytes in the kidney. ATP depletion-recovery of porcine proximal tubular epithelial cells resulted in decreased IL-6 and IL-10 levels, and MnTMPyP partially restored these cytokines. CONCLUSIONS: These results show that MnTMPyP is partially effective in reducing inflammation associated with renal IR and that reactive oxygen species play a role in modulating both pro- and anti-inflammatory pathways in acute kidney injury.
Authors: J Deng; Y Kohda; H Chiao; Y Wang; X Hu; S M Hewitt; T Miyaji; P McLeroy; B Nibhanupudy; S Li; R A Star Journal: Kidney Int Date: 2001-12 Impact factor: 10.612
Authors: P K Chatterjee; S Cuzzocrea; P A Brown; K Zacharowski; K N Stewart; H Mota-Filipe; C Thiemermann Journal: Kidney Int Date: 2000-08 Impact factor: 10.612
Authors: Huan Ling Liang; Gail Hilton; Jordan Mortensen; Kevin Regner; Christopher P Johnson; Vani Nilakantan Journal: Am J Physiol Renal Physiol Date: 2008-12-17
Authors: Xiu-Da Shen; Bibo Ke; Yuan Zhai; Feng Gao; Sei-Ichiro Tsuchihashi; Charles R Lassman; Ronald W Busuttil; Jerzy W Kupiec-Weglinski Journal: Liver Transpl Date: 2007-10 Impact factor: 5.799
Authors: Sang Jun Han; Hee-Seong Jang; Mi Ra Noh; Jinu Kim; Min Jung Kong; Jee In Kim; Jeen-Woo Park; Kwon Moo Park Journal: J Am Soc Nephrol Date: 2016-11-07 Impact factor: 10.121
Authors: Zhen Wang; Joseph H Holthoff; Kathryn A Seely; Elina Pathak; Horace J Spencer; Neriman Gokden; Philip R Mayeux Journal: Am J Pathol Date: 2011-11-24 Impact factor: 4.307