Background: Hind limb ischemia/reperfusion injury (I/R) inducing testicular damage is a medical urgency that requires urgent intervention. Aim of the work: to investigate involvement of HMGB1 and the effect of Lipoxin-A 4 (LX A4) on remote testicular injury caused by hind limb (I/R). Methods: 45 adult male Wister rats were divided into 3 equal
groups; sham-operated group, untreated hind limb (I/R) group and LXA4 pretreated hind limb (I/R) group. Malondialdehyde (MDA), catalase activity, nitrite/ nitrate, tumor necrosis factor-alpha (TNF- α), caspase-3 activity and high mobility group box-1 protein (HMGB-1) concentration and its relative mRNA expression were measured in testicular tissue. Serum level of free testosterone was also measured. Histopathological examination of testicular tissue was done as well as caspase-3 activity. Results: The untreated hind limb (I/R) injury group showed significant increase in testicular MDA, nitrite/ nitrate, TNF-α, caspase-3, as well as relative mRNA expression and concentration of HMGB-1, with significant reduction of testicular catalase activity and serum free testosterone. These biochemical results were significantly reversed in LXA4 pretreated hind limb (I/R) group. In addition there was significant negative correlation between serum free testosterone level and either HMGB1 concentration and its relative mRNA expression, testicular MDA, nitrite/nitrate, TNF-α
and caspase-3 activity and significant positive correlation with catalase activity. These results were corroborated by immunehistochemistry of caspase-3 and histopathological results of testicular tissue. Conclusion: HMGB1 has a role in pathophysiology in I/R remote injury of testis and LXA4may play an important ameliorative effect on it due to antioxidant, anti-inflammatory, antiapoptotic effects and its ability to increase NO production