Effect of Experimental Renal Ischemia Reperfusion Injury on Hypothalamic-Pituitary-Gonadal Axis in Male Rats: Role of Hypoxia Inducible Factor-1a (HIF-1a)
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- Category: Vol. 82, December 2014
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Effect of Experimental Renal Ischemia Reperfusion Injury on Hypothalamic-Pituitary-Gonadal Axis in Male Rats: Role of Hypoxia Inducible Factor-1a (HIF-1a), SAMIA M. ELEWA and MAHA M. ATTIA
Abstract
Background: Renal ischemia-reperfusion (I/R) is an important Etiopathological mechanism of acute renal failure (ARF). It occurs during renal transplantation and leads to reduced allograft survival. Deterioration of kidney function is associated with disturbance in hypothalamic-pituitary-gonadal (HPG) axis. Hypoxia-inducible factor-1a (HIF-1a) plays an essential role in cellular and systemic oxygen ho-meostasis. It is also believed to be a key component of the cellular response to hypoxia and ischemia under Pathophysi-ological conditions. However, its role in renal ischemia is still controversial.
Aim of the Study: This study was carried out to inves-tigate the effect of renal Ischemia Reperfusion Injury (IRI) on hypothalamic-pituitary-gonadal axis, and its relation to HIF-1a.
Material and Methods: Fifty adult male albino rats were divided into five groups. Control group, renal ischemic groups (unilateral and bilateral) groups (II and IV), two ischemia/ reperfusion groups (unilateral and bilateral) in which ischemia is followed by 24h reperfusion groups (III and V). Kidney function tests (urea, creatinine and cystatin C), serum levels of HIF-1a, Nitric Oxide (NO), and hypothalamic-pituitary-gonadal hormones (prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone) were measured.
Results: Serum urea, creatinine and cystatin C were significantly elevated in both ischemic and IRI groups as compared with control p<0.001. HIF-1a levels were signifi-cantly elevated in both ischemic and IRI groups as compared with control, although its levels were more elevated in IRI groups. Significant reduction in NO levels was detected in both ischemic and IRI groups. Significant elevation in prolactin, FSH and LH was detected in both ischemic and IRI groups. On the other hand, significant reduction in testosterone was observed in the same groups. Significant positive correlation between HIF-1a and both of prolactin in bilateral ischemic group with r=0.661 & p=0.038 and FSH in unilateral IRI groups with r=0.964 & p<0.001 were detected. HIF-1a was positively correlated with LH in both ischemic groups (uni & bilateral) and unilateral IRI group, with r=0.936, 0.790 & 0.80 and p<0.001, =0.007 & 0.005 respectively. On the other hand, HIF-1a was negatively correlated with testosterone in all ischemic and IRI groups.
Conclusion: The results of the present study provide evidence that activation of HIF-1a is a part of homeostatic response to the deleterious effects of renal ischemic injury. HIF-1a expression in renal pathological conditions could prove useful in providing further insight into the role of hypoxia in the progression of renal ischemia. HIF-1a elevation not only indicates cellular hypoxia but also modulates the extent of hypoxic injury. It was also associated with disturbance of male sex hormone production in response to IRI. So, exogenous modulation of HIF-1a may represent a new ther-apeutic approach to prevent testosterone suppression in re-sponse to IRI.