Abstract

AMELIORATION OF PARAQUAT-INDUCED CEREBRAL INJURY BY THE ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITOR (SACUBITRIL/VALSARTAN) VIA TARGETING INFLAMMATION & OXIDATIVE STRESS

Nourhane M. Elemam*, Manar A. Nader and Marwa E. Abdelmageed

ABSTRACT

Background: Paraquat (PQ) is a nonselective herbicide that is widely used especially in developing countries. The present study focussed on the cerebral damage caused by PQ and the efficacy of (sacubitril/valsartan), the angiotensin receptor neprilysin inhibitor (ARNI) in mitigation of such neurodegeneration. Methods: Rats were divided into five groups: control, ARNI, PQ, ARNI 64 + PQ, ARNI 32 + PQ. Brain tissues were separated after euthanasia and histopathological examination was performed. Additionally, oxidative stress biomarkers and inflammatory markers: nuclear factor kappa B (NF-κB), Tumour necrosis factor α (TNFα), and interleukin 1beta (IL-1β) were assessed using ELISA technique. Results: PQ group showed an ultimately abnormal alterations in brain structure, beside extremely high levels of malondialdehyde (MDA) along with low levels of reduced glutathione (GSH), and total antioxidant capacity (TAC).Moreover, inflammatory biomarkers, NF-κB, TNFα, and IL-1β were abnormally elevated. However, ARNI-treated groups reversed all alterations precipitated by PQ in a dose dependent manner. Conclusion: ARNI could attenuate cerebral degeneration induced by PQ via suggested antioxidant anti-inflammatory properties.

Keywords: Paraquat, ARNI, oxidative stress, NF-?B.