Administration of minocycline ameliorates damage in a renal ischemia/reperfusion injury model.

PURPOSE

The purpose of this study was to investigate the effects of minocycline on the renal dysfunction and injury caused by bilateral ischemia/reperfusion (I/R) of murine kidneys in vivo.

METHODS

Male C57BL/6 mice were administered minocycline (45 mg/kg i.v.) or saline (0.9%, v/v, NaCl) 36 hours prior to I/R. Mice were subjected to bilateral renal ischemia (35 min) followed by reperfusion (6 hours). Serum creatinine (sCr) and blood urea nitrogen (BUN) levels were measured. Additionally, renal superoxide dismutase (SOD) levels, malondialdehyde (MDA) levels and myeloperoxidase (MPO) activity were determined. The expression of intercellular adhesion molecule-1 (ICAM-1), caspase-3, caspase-8 and caspase-9 was determined using real time RT-PCR and Western blot analysis.

RESULTS

Minocycline administration significantly reduced the increases in sCr and BUN caused by I/R, indicating attenuation of renal dysfunction and injury, and reduced histological evidence of renal damage caused by I/R. Minocycline administration also markedly reduced the evidence of oxidative stress (MPO activity, SOD and MDA levels), inflammation (ICAM-1 expression and MPO activity) and apoptosis (caspase-3, caspase-8 and caspase-9 expression) in mouse kidneys subjected to I/R.

CONCLUSION

These findings provide good evidence that minocycline can reduce the renal dysfunction and injury caused by I/R of the kidney. Its mechanism may involve suppression of apoptosis, inflammatory response and oxidative stress.