The generation of endogenous
hydrogen sulphide may either limit or contribute to the degree of tissue injury caused by ischaemia/
reperfusion injury. Here, we have attempted to characterise the endogenous
hydrogen sulphide synthesis pathway and the effects of
sodium hydrosulphide, a
hydrogen sulphide donor, in a mouse model of renal ischaemia/
reperfusion injury. Anaesthetised male C57/b mice weighing 20-25 g were divided into two groups; (i) 'Ischaemia/
Reperfusion Injury', in which mice were subjected to bilateral renal ischaemia performed by clamping the renal pedicles for 30 min followed by reperfusion for 24 h, (ii) '
Sham', in which mice were subjected to the same
surgical procedures as above, except for renal ischaemia/reperfusion. Western blot analysis of the kidney taken at the end of the experiment demonstrated that
cystathionine gamma-lyase, the
enzyme responsible for generating
hydrogen sulphide in the cardiovascular system, is expressed in the normal kidney and is significantly increased after ischaemia/
reperfusion injury. Ischaemia/
reperfusion injury significantly increased the rate of
hydrogen sulphide production in kidney homogenates and increased the plasma concentration of
hydrogen sulphide. In addition, we have shown that administration of the
hydrogen sulphide donor
sodium hydrosulphide (100 micromol/kg) 30 min prior to ischaemia and 6 h into reperfusion significantly attenuated ischaemia/
reperfusion injury-induced renal dysfunction indicated by serum
creatinine and
urea. These findings suggest that
hydrogen sulphide protects the kidney against ischaemia/
reperfusion injury and that the increase in expression of the
enzyme cystathionine gamma-lyase during ischaemia/
reperfusion injury may be one of many endogenous mechanisms to limit renal ischaemia/
reperfusion injury.