Abstract

Chronic renal failure (CRF) is a rapidly growing global health problem and it causes anaemia and cognitive impairment. Recombinant Human erythropoietin (rHu-Epo) has been a promising role in the management of anaemia in CRF subjects and it is well documented. It also shown as a remarkable neuroprotection in both cell cultures and in animal models. Creatine kinase (CK) plays a key role in energy metabolism and its activity found in cytoplasm of several human tissues; major sources of CK include skeletal muscle, myocardium and brain. Studies show brain energy metabolism is key to neuronal cell function and cognitive health. The aim of this study is to investigate the impact of rHu-Epo on CRF induced changes in CK system in serum and brain regions of experimental animals and to test its significance in neurobehavioral changes. Experimental design is divided into two phases to find out the variation between simultaneous and post rHu-Epo Treatment in CRF induced male wistar rats. At the end of 40 days, animals were sacrificed uniformly. In both phases, CK level in serum and selected brain regions such as cerebellum, cerebral cortex and hippocampus were determined by spectrophotometric method and hematological parameters (RBC, Hb, PCV, MCV, MCH, MCHC) were also determined. In results, decreased creatine kinase activity in brain regions and its increased level in serum observed in CRF induced animals. Neurobehavioral changes and alterations in hematological parameters were also seen in CRF induced animals. Supplementation of rHu-Epo in both simultaneous and post treatment group reversed the CRF induced changes including neurobehavioral alterations, significantly. In this study, the protective role of Epo supplementation on CRF induced changes in CK system in both brain and serum and its correlation with neurobehavioral changes were seen along with its antianemic effect.

Highlights

  • Chronic renal failure (CRF) is a global health problem, that causes widespread organ damage and it is related to significant morbidity and mortality [1]

  • The blood urea nitrogen (BUN) and serum creatinine levels were significantly increased in CRF induced groups when compared to control (p value

  • There is a significantly decreased levels of above mentioned hematological parameters were observed in CRF induced animals

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Summary

Introduction

Chronic renal failure (CRF) is a global health problem, that causes widespread organ damage and it is related to significant morbidity and mortality [1]. CRF encompasses a spectrum of disease, ranging from mild kidney damage which can be asymptomatic, to end stage disease, in which kidney function is impaired to such an extent that the retention of metabolic waste products, salt and water become potentially fatal [2]. Many studies have shown that, CRF is associated with uremic encephalopathy and cognitive impairment. Cognition refers to a range of brain functions that include the ability to learn and remember, think through and plan activities, concentrate and carry out tasks. The cerebral cortexes is the outer most part of brain and its many areas process sensory information or coordinate motor output necessary for control of movement. Cerebellum controls equilibrium and the coordination of fine motor movements, and may be involved in some cognitive functions. The hippocampus located in the middle of the brain, is a key structure associated with memory

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