title: Pharmacological inhibition of CXCR2 chemokine receptors modulates paraquat-induced intoxication in rats.
abstract: Paraquat (PQ) is an agrochemical agent commonly used worldwide, which is allied to potential risks of intoxication. This herbicide induces the formation of reactive oxygen species (ROS) that ends up compromising various organs, particularly the lungs and the brain. This study evaluated the deleterious effects of paraquat on the central nervous system (CNS) and peripherally, with special attempts to assess the putative protective effects of the selective CXCR2 receptor antagonist SB225002 on these parameters. PQ-toxicity was induced in male Wistar rats, in a total dose of 50 mg/kg, and control animals received saline solution at the same schedule of administration. Separate groups of animals were treated with the selective CXCR2 antagonist SB225002 (1 or 3 mg/kg), administered 30 min before each paraquat injection. The major changes found in paraquat-treated animals were: decreased body weight and hypothermia, nociception behavior, impairment of locomotor and gait capabilities, enhanced TNF-α and IL-1β expression in the striatum, and cell migration to the lungs and blood. Some of these parameters were reversed when the antagonist SB225002 was administered, including recovery of physiological parameters, decreased nociception, improvement of gait abnormalities, modulation of striatal TNF-α and IL-1β expression, and decrease of neutrophil migration to the lungs and blood. Taken together, our results demonstrate that damage to the central and peripheral systems elicited by paraquat can be prevented by the pharmacological inhibition of CXCR2 chemokine receptors. The experimental evidence presented herein extends the comprehension on the toxicodynamic aspects of paraquat, and opens new avenues to treat intoxication induced by this herbicide.
authors.affiliation: Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre/RS, Brazil.
authors.forename: Kesiane M
authors.initials: KM
authors.lastname: Costa
authors.affiliation: Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre/RS, Brazil.
authors.forename: Izaque S
authors.initials: IS
authors.lastname: Maciel
authors.affiliation: Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre/RS, Brazil; Laboratory of Genomics and Molecular Biology, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre/RS, Brazil.
authors.forename: Luiza W
authors.initials: LW
authors.lastname: Kist
authors.affiliation: Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre/RS, Brazil; Institute of Toxicology and Pharmacology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre/RS, Brazil; Faculty of Dentistry, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre/RS, Brazil.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Campos
authors.affiliation: Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre/RS, Brazil; Laboratory of Genomics and Molecular Biology, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre/RS, Brazil; Postgraduate Program in Cellular and Molecular Biology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre/RS, Brazil.
authors.forename: Maurício R
authors.initials: MR
authors.lastname: Bogo
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005684:Gait / Q000187:drug effects; D006540:Herbicides / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology*; D010671:Phenylurea Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018925:Chemokines; D006540:Herbicides; D053583:Interleukin-1beta; D010671:Phenylurea Compounds; D017382:Reactive Oxygen Species; D023063:Receptors, Interleukin-8B; C112019:SB 225002; D014409:Tumor Necrosis Factor-alpha; D010269:Paraquat