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Therapeutic Effects of Corm3 and Nahs in Chronic Kidney Disease Induced Cognitive Impairment Via the Interaction Between Carbon Monoxide and Hydrogen Sulfide on Nrf2/Ho-1 Signaling Pathway in Rats Publisher Pubmed



Hamidizad Z1 ; Kadkhodaee M1 ; Karimian SM1 ; Ranjbaran M1 ; Heidari F2 ; Bakhshi E3 ; Kianian F1 ; Zahedi E1 ; Seifi B1
Authors
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Authors Affiliations
  1. 1. Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Anatomy, School of Medicine, Qom University of Medical Sciences, Qom, Iran
  3. 3. Department of Statistics and Computer, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran

Source: Chemico-Biological Interactions Published:2022


Abstract

Cognitive impairment is one of the major complications of chronic kidney disease (CKD). The present study aims to evaluate the protective effects of carbon monoxide (CO) and hydrogen sulfide (H2S) and their interactions on CKD-induced cognitive deficits by considering the Nrf2/HO-1 signaling pathway. Sixty rats were divided into six experimental groups: sham, five-sixth (5/6) nephrectomy (CKD), CKD + H2S donor (NaHS), CKD + CO-releasing molecule (CORM3), CKD + NaHS and zinc protoporphyrin IX (Znpp), CKD + CORM3 and amino-oxy acetic acid (AOAA). Eleven weeks after 5/6Nx, behavioral tests (Novel object recognition test, Passive avoidance test and Barnes maze test) were performed to evaluate the cognitive level. At the end of the twelfth week, blood urea nitrogen (BUN) and serum creatinine (sCr) levels, as well as the expression levels of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and neuronal loss in the hippocampus and prefrontal cortex were evaluated. CKD caused enhancement of BUN and sCr, reduction of Nrf2 and HO-1 proteins and enhancement of neuronal loss in the hippocampus and prefrontal cortex. In addition, CKD led to cognitive disturbances and memory impairment. CORM3 and NaHS returned all above indices to the levels measured in the control group. However, improving effects of CORM3 on cognitive impairment and Nrf2/HO-1 signaling pathway were prevented by AOAA and decreased H2S level as well as reciprocally improving effects of NaHS on cognitive disturbances and Nrf2/HO-1 signaling pathway were prevented by Znpp and decreased CO level. In conclusion, this study demonstrated that formation of CO and H2S were interdependently improved CKD-induced cognitive dysfunctions, through interaction with Nrf2/HO-1 signaling pathway. © 2022 Elsevier B.V.
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