N-acetylcysteine (NAC) alleviates the peripheral neuropathy associated with liver cirrhosis via modulation of neural MEG3/PAR2/ NF-ҡB axis.

Autor: Mohamed DI; Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: doaapharma@yahoo.com., Khairy E; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: dr_emankhairy@yahoo.com., Khedr SA; Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: sara_adel08@yahoo.com., Habib EK; Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: emanhabib75@gmail.com., Elayat WM; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: wael_elayat@hotmail.com., El-Kharashi OA; Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: omnyah2011@gmail.com.
Jazyk: angličtina
Zdroj: Neurochemistry international [Neurochem Int] 2020 Jan; Vol. 132, pp. 104602. Date of Electronic Publication: 2019 Nov 18.
DOI: 10.1016/j.neuint.2019.104602
Abstrakt: Background and Aim: Oxidative stress (OS) is accused in pathogenesis of many diseases, including liver cirrhosis by many mechanisms. One of them is the disturbance of long non coding maternally expressed 3 (MEG3)/protease activated receptor 2 (PAR2) downstream pathway. We aimed to investigate the role of this axis in cirrhotic neuropathy and whether an antioxidant compound such as N-acetylcysteine (NAC) could improve the peripheral nerve function through repression of MEG3/PAR2.
Methods: Thirty Wistar rats were used and divided into 5 groups; naive, thiacetamide (TAA) (200 mg/kg 3 times/week. i.p. for 8 weeks) and TAA+NAC (50 or 100 or 200 mg/kg/day) groups. Von Frey (VF) test for mechanical nociceptive responses, hepatic& neural MEG3, NF-ҡB and neural PAR2 expression by PCR, histological studies for liver and sciatic nerve together with the dorsopedal skin thickness were done.
Results: TAA induced significant decrease in liver function, negative VF test, an increase in the expression of hepatic& neural MEG3, NF-ҡB and neural PAR2. The histological studies showed cirrhotic changes with atrophy of the sciatic nerve and the dorsal skin. NAC improved the liver function together with reversal of the neural: functional, biochemical and histological changes in a dose dependent manner.
Conclusions: NAC could improve the peripheral neuropathy in cirrhotic rat through suppression of MEG3/PAR2 expression.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: