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acute renal failure ( arf ) or acute kidney injury includes a wide range of disturbance in kidney function .
renal ischemia / reperfusion injury ( riri ) which occurs mainly in different clinical circumstances such as renal transplantation is responsible for high morbidity and mortality rate .
endothelin-1 ( et-1 ) as one of the most known potent vasoconstrictors is up - regulated during renal ischemia , so it increases renal vascular resistance and causes reduction in renal blood flow after reperfusion .
et-1 seems to exacerbate riri , because administration of bosentan ( bos ) - a dual et-1 receptor antagonist demonstrated protective effects on experimental riri . et-1 and
therefore , et-1 is probably a key mediator in the maintenance of gender - mediated differences after riri . in this short study ,
groups 1 ( male , n = 6 ) and 2 ( female , n = 6 ) as sham - operated were subjected to surgery without ischemia . the groups 3 ( male , n = 6 ) and 4 ( female , n = 6 ) received saline as vehicle 2 h before induction of ischemia .
groups 5 ( male , n = 6 ) and 6 ( female , n = 6 ) were treated similar to groups 3 and 4 except they received bos ( 50 mg / kg ) instead of vehicle .
twenty - four hours postreperfusion , the animal was anesthetized again , and blood samples were obtained via heart puncture . after sacrificing the animals ,
the serum levels of creatinine ( cr ) and blood urea nitrogen ( bun ) were measured by quantitative diagnostic kits ( pars azmoon , tehran , iran ) .
serum and tissue levels of nitrite were measured by an assay kit ( promega corporation , usa ) that involves the griess reaction .
the data were expressed as mean  standard error of mean the groups were compared in terms of the serum levels of bun , cr , nitrite , and mda ; and tissue nitrite and mda levels and kidney weight ( kw ) using the one - way analysis of variance followed by the least significant difference test .
the serum levels of creatinine ( cr ) and blood urea nitrogen ( bun ) were measured by quantitative diagnostic kits ( pars azmoon , tehran , iran ) .
serum and tissue levels of nitrite were measured by an assay kit ( promega corporation , usa ) that involves the griess reaction .
the data were expressed as mean  standard error of mean the groups were compared in terms of the serum levels of bun , cr , nitrite , and mda ; and tissue nitrite and mda levels and kidney weight ( kw ) using the one - way analysis of variance followed by the least significant difference test .
riri significantly increased the serum levels of bun and cr in both genders when compared with the sham operated groups .
serum levels of blood urea nitrogen and creatinine , and kidney weight per 100 g body weight in three experimental groups of sham , ischemia and ischemia treated with bosentan in male and female rats .
star ( * ) and ( # ) indicate significant differences ( p < 0.05 ) from sham or ischemia group , respectively .
n = 6 in each group kw was significantly increased by the riri , and it was significantly decreased by bos in female rats [ figure 1 ] .
body weight change indicated no significant difference between the males and females groups [ table 1 ] .
sn ( mole / l ) and smda ( mole / l ) , kn ( mole / g tissue ) and kmda(nanomole / g tissue ) , and w ( g ) in three experimental groups of sham , ischemia and ischemia treated with bos in male and female rats there were significant differences in serum and kidney levels of mda in male but not those of female .
neither male nor female groups demonstrated no significant changes in serum and kidney levels of nitrite [ table 1 ] .
riri significantly increased the serum levels of bun and cr in both genders when compared with the sham operated groups .
serum levels of blood urea nitrogen and creatinine , and kidney weight per 100 g body weight in three experimental groups of sham , ischemia and ischemia treated with bosentan in male and female rats .
star ( * ) and ( # ) indicate significant differences ( p < 0.05 ) from sham or ischemia group , respectively .
kw was significantly increased by the riri , and it was significantly decreased by bos in female rats [ figure 1 ] .
body weight change indicated no significant difference between the males and females groups [ table 1 ] .
sn ( mole / l ) and smda ( mole / l ) , kn ( mole / g tissue ) and kmda(nanomole / g tissue ) , and w ( g ) in three experimental groups of sham , ischemia and ischemia treated with bos in male and female rats
there were significant differences in serum and kidney levels of mda in male but not those of female .
neither male nor female groups demonstrated no significant changes in serum and kidney levels of nitrite [ table 1 ] .
riri is the first most common cause of inpatient 's arf . over the past years
, studies have identified a variety of methods to treat renal riri . in the present study
, we attempted to investigate the gender - related effect of bos as et-1 blocker on renal riri .
our results showed that renal ischemia - reperfusion induced renal failure that characterized by increasing bun and cr as well as kw in both genders .
there are some reports suggesting that et-1 is involved in the development of postischemic arf in clinical transplantation .
recent studies suggest the importance of enhanced renal production of et-1 in the pathogenesis of ischemic arf .
for example , plasma et-1 levels are elevated in arf , and renal ischemia increases renal et-1 content and et receptor affinity
. infusion of et-1 decreases glomerular filtration rate , renal blood flow , sodium excretion and increases filtration fraction and renal vascular resistant while co - injection of vml 588 ( et - a antagonist ) will reduce all sequences except glomerular filtration rate .
. showed that et-1 contributes to experimental renal cold ischemia - reperfusion injury , and bos can attenuate this injury .
the present study showed that pretreatment with bos as a nonselective dual eta / etb receptor antagonist could attenuate post - ischemic renal injury in both genders .
moreover , several investigators have noted that exogenous monoclonal or polyclonal antibody to et , eta receptor antagonists , or eta / etb dual receptor antagonists ameliorated declines in glomerular filtration rate and tubular damage in ischemia - reperfusion injury .
bos was shown to have a beneficial effect on experimental ischemia / reperfusion injury in the spinal cord , testis , heart and kidney .
it was showed that bos treated rats had higher renal blood flow , cr clearance , glomerular filtration rate and lower plasma cr after riri .
also , administration of an et receptor antagonist 24 h after the ischemic damage was highly effective in reversing arf .
despite sexual dimorphism in the majority of physiological and pathophysiological conditions , the majority of experiments on ischemia - induced arf have been conducted in male animals only .
the course of post - ischemic renal failure has not been systematically compared between males and females . therefore in this study to gain further insights into the role of gender in ischemic renal damage , we compared this process in male and female rats .
there is identified that female mice were more resistant to renal insulin receptor ( ir ) injury compared with male mice .
williams et al . measured the serum level of bun and cr levels for 0 , 0.5 , 1 , 2 , 4 , 6 , 9 , and 24 h and 1 week post - riri , and reported that the earliest renal injury started at the 4 h following ischemia and peaked at the 1 day .
commonly used definitions of arf include an increase in serum cr , a reduction in the calculated cr clearance of 50% , or a decrease in renal function that results in the need for dialysis .
however , serum cr production changes significantly according to age , sex , muscle mass and dietary intake . the possible effect of sex on serum cr level might be one of the reasons that we did not infer any significant difference in cr level among different genders .
by contrast , mller et al . suggested that gender has a major impact on ischemia - induced renal damage and sex hormones play a crucial role in this difference .
sex hormones have been reported to have an important role in i / r - induced inflammatory processes in the kidneys .
previous studies have demonstrated that testosterone has an important role in increasing the susceptibility to ischemic renal injury .
by contrast , other experimental results suggest that estrogen has a protective effect in ischemic renal injury in female via suppression of et-1 production and activation of the phopsphatidylinositol-3 kinase / protein kinase b signaling pathway .
our result showed no difference in nitrite level between the male and female groups , and kidney mda level reduced only in male , but other study showed that kidney mda level decreased in male and female ischemic animals , and ir decreased serum and kidney level of nitrite .
we conclude that bos can be used in both genders to attenuate injury induced in kidney ischemia possibly due to its effect in the renal vascular system .
background : renal ischemia / reperfusion injury ( riri ) is the most common cause of acute kidney injury . 
 we tested the protective role of endothelin-1 receptor blocker ; bosentan ( bos ) in animal model of riri in two different genders.methods:male and female wistar rats were assigned as sham operated ( sham ) , control group ( ischemia ) , and case group ( ischemia + bos ) treated with bos ( 50 mg / kg ) 2 h before bilateral kidney ischemia induced by clamping renal vessels for 45 min followed by 24 h of renal reperfusion.results:the riri significantly increased the serum levels of blood urea nitrogen and creatinine in both genders ( p < 0.05 ) . 
 these values were significantly decreased by bos in both genders . in male rats , 
 the serum levels of malondialdehyde in the ischemia + bos group were decreased significantly when compared with ischemia group ( p < 0.05).conclusions : bos can be used in both genders to attenuate kidney ischemia injury possibly due to its effect in the renal vascular system .