John_2019_Life.Sci_228_98

AIMS: Protective efficacy of Nacetylcysteine (NAC) was assessed against sub-acute diisopropyl phosphorofluoridate (DFP) poisoning in mice. MAIN METHODS: Mice were allocated into nine groups of six each: vehicle control; DFP (0.125 LD50 approximately 0.483mg/kg bwt, s.c.); DFP+Atropine (ATR, 10mg/kg bwt, i.p., 0min); DFP+Pralidoxime (2-PAM, 30mg/kg bwt, i.m., 0min); DFP+NAC (150mg/kg bwt, i.p., -60min); DFP+ATR+NAC; DFP+2-PAM+NAC; DFP+ATR+2-PAM; and DFP+ATR+2-PAM+NAC. Animals received various treatments for 21d daily. Plasma butyrylcholinesterase (BChE) was measured after 7, 14 and 21d of exposure. Brain acetylcholinesterase (AChE) and reduced glutathione (GSH), malondialdehyde (MDA), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD) were measured (brain, liver and kidney) after 21d of exposure. Histopathology, immunohistochemistry, and Western blot for inducible nitric oxide synthase (iNOS) and c-fos were also performed. KEY FINDINGS: DFP significantly reduced BChE and AChE levels. Diminished GSH, CAT, SOD (brain and liver), GPx, GR, and elevated MDA (Brain) levels were also observed. DFP caused notable histopathology (brain, liver and kidney) and over expression of iNOS, and c-fos proteins (brain). NAC enhanced the protective efficacy of ATR and 2-PAM in most parameters, without any appreciable protection in iNOS and c-fos expression. SIGNIFICANCE: NAC as an adjunct with ATR and 2-PAM, exhibited marked beneficial effects against sub-acute DFP poisoning, indicating its possible implications in the management of OP poisoning.