Possible Effects of Mirabegron on Rat Liver in Renal Ischemia Reperfusion Injury: Histological and Immunohistochemical Studies

Liver and kidney are both critical controller organs in our body and any liver or kidney damage including 
organ ischemia, may affect the other. Renal ischemia reperfusion injury diminishes antioxidant protein 
and increases neutrophils and lymphocytes amassing in liver tissue. Mirabegron is a medication used to 
treat overactive bladder. It works by activating the β3 adrenergic receptor in the bladder, resulting in its 
relaxation. We aimed in this study to investigate the possible histological and immmunohistochemical 
effects of mirabegron on the rat liver in cases of induced renal ischemia reperfusion injury. Fifteen rats 
were used and randomly classified into 5 groups, 10 rats each. Control group in which the rats received 
the vehicle; CMC without any surgical procedures. Sham group in which the rats received the vehicle 
then undergone laboratomy without ligation of renal pedicle. Mirabegron group in which the rats received
0.3mg/kg mirabegron without surgical procedures. Renal Ischemia Reperfusion group (RIR), rats 
administered the vehicle, after which ischemia induced (30 min) followed by reperfusion (3 hours). 
Mirabegron + RIR group in which the rats pretreated with 0.3 mg/kg mirabegron then RIR induced using 
the same procedures as that for the RIR group. The liver tissues from all groups were collected and then 
processed for histological and iNOs immunohistological studies.Liver sections from RIR rats showed loss 
of normal architecture of hepatic lobules in the form of congested central vein, restricted inflammatory 
cell infiltration and dilated hepatic sinusoids. Most of hepatocytes looked vacuolated with eccentric nuclei 
and others showed pyknotic dense nuclei. In comparison, pretreating the RIR rats with mirabegron 
showed restoration of the normal architecture of the hepatic lobules to great extent. Positive iNOS 
immunostaining in hepatocytes of RIR rats was noticed and pretreating the RIR rats with mirabegron 
reversed this positivity. We can conclude that mirabegron has a protective role on the rat liver in induced 
renal ischemia reperfusion injury.