The effect of humanin on rat renal ischemia reperfusion model

Objective: Ischemia/reperfusion (I/R) injury causes acute tubular necrosis and renal failure, initiates mechanisms such as inflammation, formation of reactive oxygen species, apoptosis and mitochondrial dysfunction. A mitochondrial-derived peptide HN has been reported to reduce oxidative stress and mitochondrial dysfunction. It has been demonstrated that HN has antiapoptotic and anti-inflammatory effects. The aim of our study is to investigate the effects of HN on renal I/R damage. Method: Sprague-Dawley male rats were divided into 4 groups (n=48); 1. Sham, 2. I/R, 3. HN-Sham, 4. HN-I/R. Pseudo-Surgery was performed in Sham groups; In I/R groups, renal artery ligation performed for 45 minutes, followed by reperfusion for 24 hours. HN treatment (2mg/kg/iv) was administered 10 minutes before reperfusion. During the 24-hour reperfusion period, the urine of the rats was collected and then the experiment was terminated by collecting blood and tissue samples. Renal functions, inflammation, oxidative stress, antioxidant capacity and mitochondrial functions were investegated Histopathological methods were used to evaluate kidney tissue damage and apoptosis. Results: Blood urea nitrogen, serum creatinine, urine albumin levels and sodium and potassium excretions were found to be high and creatine clearance was low in the I/R group and; were not affected by HN treatment. Glutathione levels, superoxide dismutase and catalase enzyme activity, which decreased in the I/R group, were significantly higher in the HN-I/R group. It was found that the myeloperoxidase activity of the I/R group was higher than the HN-I/R group. Adenosine triphosphate levels and mitochondrial complex 1 activity levels were higher in the HN-I/R group than in the I/R group. It was determined that the increased percentage of apoptotic cells in the I/R group decreased significantly in the HN-I/R animals. Conclusion: HN may play a role to attenuating renal I/R damage by reducing oxidative stress, inflammation and apoptosis, improving antioxidant capacity and mitochondrial functions.