Abstract
Systemic hypobaric hypoxia is reported to cause renal damage; nevertheless the exact pathophysiological mechanisms are not completely understood. Therefore, the present study aims to explore renal pathophysiology by using proteomics approach under hypobaric hypoxia. Six to eight week old male Sprague Dawley rats were exposed to hypobaric hypoxia equivalent to altitude of 7628 metres (pO2-282mmhg) at 28°C and 55% humidity in decompression chamber for different time intervals; 1, 3, and7 days. Various physiological, proteomic and bioinformatic studies were carried out to examine the effect of chronic hypobaric hypoxia on kidney. Our data demonstrated mild to moderate degenerative tubular changes, altered renal function, injury biomarkers and systolic blood pressure with increase in duration of hypobaric hypoxia exposure. Renal proteomic analysis showed 38 differential expressed spots, out of which 25 spots were down regulated and 13 were up regulated in 7 dayhypobarichypoxic exposure group of rats as compared to normoxia control. Identified proteins were involved in specific molecular changes pertinent to endogenous redox pathways, cellular integrity and energy metabolism. The study provides an empirical evidence of renal homeostasis under hypobaric hypoxia by investigating both physiological and proteomics changes. The identification of explicit key proteins provides a valuable clue about redox signalling mediated renal damage under hypobaric hypoxia.
Highlights
Hypoxia occurs when tissue supply of oxygen is decreased and it is encountered in many pathophysiological conditions, such as atherosclerosis, obstructive sleep apnea, mountain sickness, ischemic diseases, cancer and during embryonic development
To understand the effect of hypobaric hypoxia, we carefully examined the kidney tissue sectioned from rats exposed to different durations (1, 3 and 7 day) of hypobaric hypoxia and normoxia control groups
Using in-vivo physiological studies coupled with proteomic analysis, we evaluated the effect of hypobaric hypoxia on renal structure, function and proteomic profile in rat model
Summary
Hypoxia occurs when tissue supply of oxygen is decreased and it is encountered in many pathophysiological conditions, such as atherosclerosis, obstructive sleep apnea, mountain sickness, ischemic diseases, cancer and during embryonic development. Hypoxia is a very important factor affecting the health and life activities of individuals at high altitude, which has serious impacts on physiology and induces pathological changes in the body [1,2]. Several high altitude studies speculate that there is an increased risk for the development of kidney dysfunction characterized by micro albuminuria, hypertension, and hyper. Many pathological conditions including chronic respiratory insufficiency, prolonged cardiovascular dysfunction, acute diabetes, hypertension, aging, renal hypertrophy, anemia and obstructive uropathy reduce renal oxygenation and results in kidney dysfunction [8]. The available clinical and experimental evidences strongly indicate that kidney is vulnerable to hypoxia and play a very important role in high altitude adaptation
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