title: Sub-chronic exposure of non-observable adverse effect dose of terbufos sulfone: neuroinflammation in diabetic and non-diabetic rats.
abstract: Neuroinflammation (NI) contributes to the pathogenesis of several neurodegenerative disorders. Epidemiological and a few animal studies have shown that chronic exposure of organophosphorus compounds (OPC) may cause neuronal injury and predispose to neuro- as well as psychotic disorders in conjunction with NI. However, in vivo studies are meager and do not represent the entire toxicologically diversified OPC. The present study aimed to investigate the result of non-observable adverse effect level dose of a highly toxic OPC, terbufos sulfone (TBS), on sub-chronic exposure on the status of proinflammatory cytokines; interleukin-1β, interleukin-6 and tumor necrosis factor-α in rats brain. In addition, lactate dehydrogenase, nitric oxide and reduced glutathione were also determined in brain. Red blood cell acetylcholinesterase was measured weekly. Total of four groups' saline control, diabetes control, non-diabetes TBS and diabetes treated with TBS were employed in the study. Control groups received saline and the experimental groups were injected with TBS intraperitonealy for fifteen days daily. Twenty four hours after the last injection, the animals were euthanized for collection of brain and serum samples. The study showed significant elevation of interleukin-6, tumor necrosis factor-α and lactate dehydrogenase in brain of TBS treated groups, while the presence of interleukin-1β was significantly greater in the non-diabetes TBS treated group when compared with saline control. The increase was observed to be independent of acetylcholinesterase level and diabetes condition. The change in reduced glutathione was modest as compared with control. Based on the findings, the study concludes that the non-observable adverse effect level dose of TBS has potential to cause NI and subsequent neurodegeneration, a remarkable sign of many chronic neuronal and psychotic disorders. Further studies with prolonged exposure and other neurodegenerative parameters are warranted.
authors.forename: Syed M
authors.initials: SM
authors.lastname: Nurulain
authors.forename: Ernest
authors.initials: E
authors.lastname: Adeghate
authors.forename: Azimullah
authors.initials: A
authors.lastname: Sheikh
authors.forename: Javed
authors.initials: J
authors.lastname: Yasin
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Kamal
authors.forename: Charu
authors.initials: C
authors.lastname: Sharma
authors.forename: Abdu
authors.initials: A
authors.lastname: Adem
authors.affiliation: Departments of Pharmacology and Therapeutics, United Arab Emirates University, P.O. Box # 17666,Al Ain, Abu Dhabi, United Arab Emirates. shreeshojha@uaeu.ac.ae.
authors.forename: Shreesh
authors.initials: S
authors.lastname: Ojha
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology* / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D009946:Organothiophosphorus Compounds; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D000110:Acetylcholinesterase; D005978:Glutathione; C036515:terbufos sulfone