Protection by Neostigmine and Atropine Against Brain and Liver Injury Induced by Acute Malathion Exposure

Abstract

We examined the effect of treatment with neostigmine alone or with atropine on brain oxidative stress and on brain and liver tissue damage following acute malathion toxicity. Rats were intraperitoneally treated with malathion 150 mg/kg along with neostigmine (200 or 400 μg/kg) or neostigmine (200 μg/kg) + atropine (1 mg/kg) and euthanized 4 h later. Results indicated that compared with the saline group, malathion resulted in (i) higher brain malondialdehyde (MDA) and nitric oxide (46.4% and 86.2%); (ii) decreased brain reduced glutathione (GSH) (67.6%); (iii) decreased brain paraoxonase-1 (PON1), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities (31.2%, 21.6% and 60%); (iv) decreased brain glucose (-38.1%); (v) neuronal degeneration in cortex and hippocampus and markedly increased glial fibrillary acidic protein (GFAP) immunostaining in the hippocampus; (v) hydropic and fatty degeneration in liver. Rats treated with malathion along with neostigmine or neostigmine + atropine showed no change in brain MDA but decreased nitric oxide (-34.2%-48%). GSH increased after neostigmine 200 μg/kg or neostigmine + atropine (35.8% and 41%). PON1 activity increased (42%-35.2%) and glucose concentrations increased (91.5%-81.5%) by 400 μg/kg neostigmine or neostigmine + atropine. Brain AChE activity remained unchanged but BChE activity showed 18.3% increment after 400 μg/kg neostigmine. Rats treated with 400 μg/kg neostigmine or neostigmine + atropine had normal neuronal appearance in cortex and hippocampus and weak GFAP expression in hippocampus. Liver damage was prevented by neostigmine + atropine. These results suggest that treatment with neostigmine + atropine afforded protection against the deleterious effects of acute malathion on the brain and liver.

Novel Protective Effects of Brilliant Blue G in Acute Malathion Toxicity

“…Organophosphorus insecticides have also been implicated in neuro-degeneration such as that occurring in Parkinson's disease [7,8] and dementia [9]. In rats, exposure to malathion causes neuronal degeneration in the cerebral cortex and hippocampus, reactive gliosis, and increased expression of glial fibrillary acidic protein (GFAP) [10][11][12]. These neurotoxic effects of organophosphates involve such pathogenetic mechanisms as oxidative/nitrosative stress [10][11][12][13][14][15], impaired mitochondrial dynamics, and compromised mitochondrial bioenergetics [16,17].…”

“…In rats, exposure to malathion causes neuronal degeneration in the cerebral cortex and hippocampus, reactive gliosis, and increased expression of glial fibrillary acidic protein (GFAP) [10][11][12]. These neurotoxic effects of organophosphates involve such pathogenetic mechanisms as oxidative/nitrosative stress [10][11][12][13][14][15], impaired mitochondrial dynamics, and compromised mitochondrial bioenergetics [16,17]. Thus, increased lipid peroxidation along with decreased reduced glutathione (GSH) levels and decreased activities of the antioxidant enzymes glutathione reductase and glutathione peroxidase (GPx) and decreased total antioxidant capacity in the brain, liver, and blood have been shown in rats treated with the organophosphate insecticide malathion [10-12, 15, 17, 18].…”

Functions of retinal astrocytes and Müller cells in mammalian myopia

“…Astrocytes are in close contact with blood vessels, and Müller cells provide radial support. Activated astrocytes can produce different mediators [ 13 ]. However, there are few reports of the relationship between retinal glial cells and myopia.…”

Retinal glial cells under hypoxia possibly function in mammalian myopia by responding to mechanical stimuli, affecting hormone metabolism and peptide secretion

“…Retinal Müller cells and astrocytes have also been abundantly tested in a variety of ocular diseases, including retinal detachment, light damage, and ischemia [9, 10] , in which they show increased glial fibrillary acidic protein (GFAP) expression and morphological changes. Activated astrocytes can produce nitric oxide, tumour necrosis factor-alpha (TNF-α), reactive oxygen species, and other neurotoxic mediators [11] . There are few reports of the relationship between retinal glial cells and myopia, although several pathological process, including oxidative stress [12] and hypoxia [13] , are associated with myopia.…”

“…The muscarinic receptors (MRs) and several non-MRs [14] found mainly in the retina and sclera have been proposed as targets of atropine. In malathion-induced brain injury, atropine decreased brain astrocyte GFAP expression by inhibiting nitric oxide rather than inhibiting brain acetylcholine esterase activity [11] . We cannot exclude that atropine may benefit myopia by targeting the glial cells.…”