{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T16:03:10Z","timestamp":1777910590971,"version":"3.51.4"},"reference-count":54,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"\u201cFundac\u00e3o para a Ci\u00eancia e Tecnologia,\u201d Portugal","award":["PTDC\/SAU-FCF\/102958\/2008"],"award-info":[{"award-number":["PTDC\/SAU-FCF\/102958\/2008"]}]},{"name":"\u201cFundac\u00e3o para a Ci\u00eancia e Tecnologia,\u201d Portugal","award":["SFRH\/BPD\/30776\/2006"],"award-info":[{"award-number":["SFRH\/BPD\/30776\/2006"]}]},{"name":"\u201cFunda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia,\u201d Portugal","award":["PTDC\/SAU-FCF\/102958\/2008"],"award-info":[{"award-number":["PTDC\/SAU-FCF\/102958\/2008"]}]},{"name":"\u201cFunda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia,\u201d Portugal","award":["SFRH\/BPD\/30776\/2006"],"award-info":[{"award-number":["SFRH\/BPD\/30776\/2006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Toxicology"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>Paraquat (PQ), a cationic nonselective bipyridyl herbicide, has been used as neurotoxicant to modulate Parkinson\u2019s disease in laboratory settings. Other compounds like rotenone (ROT), a pesticide, and 1-methyl-4-phenylpyridinium ion (MPP<jats:sup>+<\/jats:sup>) have been widely used as neurotoxicants. We compared the toxicity of these three neurotoxicants using differentiated dopaminergic SH-SY5Y human cells, aiming to elucidate their differential effects. PQ-induced neurotoxicity was shown to be concentration and time dependent, being mitochondrial dysfunction followed by neuronal death. On the other hand, cells exposure to MPP<jats:sup>+<\/jats:sup>induced mitochondrial dysfunction, but not cellular lyses. Meanwhile, ROT promoted both mitochondrial dysfunction and neuronal death, revealing a biphasic pattern. To further elucidate PQ neurotoxic mechanism, several protective agents were used. SH-SY5Y cells pretreatment with tiron (TIR) and 2-hydroxybenzoic acid sodium salt (NaSAL), both antioxidants, and<jats:italic>N<\/jats:italic><jats:sub><jats:italic>\u03c9<\/jats:italic><\/jats:sub>-nitro-L-arginine methyl ester hydrochloride (L-NAME), a nitric oxide synthase inhibitor, partially protected against PQ-induced cell injury. Additionally, 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenyl-propyl)piperazine (GBR 12909), a dopamine transporter inhibitor, and cycloheximide (CHX), a protein synthesis inhibitor, also partially protected against PQ-induced cell injury. In conclusion, we demonstrated that PQ, MPP<jats:sup>+<\/jats:sup>, and ROT exerted differential toxic effects on dopaminergic cells. PQ neurotoxicity occurred through exacerbated oxidative stress, with involvement of uptake through the dopamine transporter and protein synthesis.<\/jats:p>","DOI":"10.1155\/2013\/347312","type":"journal-article","created":{"date-parts":[[2013,3,20]],"date-time":"2013-03-20T21:00:58Z","timestamp":1363813258000},"page":"1-10","source":"Crossref","is-referenced-by-count":28,"title":["Differential Effects of Methyl-4-Phenylpyridinium Ion, Rotenone, and Paraquat on Differentiated SH-SY5Y Cells"],"prefix":"10.1155","volume":"2013","author":[{"given":"Jo\u00e3o Barbosa","family":"Martins","sequence":"first","affiliation":[{"name":"REQUIMTE (Rede de Qu\u00edmica e Tecnologia), Laborat\u00f3rio de Toxicologia, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Maria de Lourdes","family":"Bastos","sequence":"additional","affiliation":[{"name":"REQUIMTE (Rede de Qu\u00edmica e 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