Immunohistochemical Localization of Paraquat in Lung and Brain

Abstract

In order to observe the localization and dynamics of paraquat in lung and brain, immunohistochemical approaches were conducted by using animals. Experimental paraquat-poisoned rats were sacrificed 3 hours, 12 hours, 24 hours, 3 days, 7 days and 10 days after intravenous administration of paraquat (5 mg/kg). In lung tissues, paraquat was localized in histiocytes, walls of blood vessels and bronchiolar epithelial cells from 3 hours to 10 days after the paraquat exposure, and interstitial pulmonary fibrosis was being developed with time. On the other hand, in brain tissues, paraquat was localized only in capillary walls and glial cells but not observed in nerve cells 10 days after the administration of paraquat.

Carrier-mediated processes in blood–brain barrier penetration and neural uptake of paraquat

“…Thus, conflicting findings on paraquat BBB penetration have been reported [23,25]. The present results using the brain microdialysis technique with the HPLC/UV detection clearly demonstrated that paraquat penetrates the BBB in a dose-dependent manner.…”

“…Although a number of clinical and experimental studies have indicated that paraquat could induce neural damage [4,8,18,32], the possibility that this herbicide itself was responsible for neurotoxic events has been challenged [23,25,39] because of its structural similarity to MPP + , which cannot penetrate into the central nervous system. In other words, the BBB penetration of paraquat has not yet been supported by the conclusive findings.…”

“…However, paraquat has induced brain damage in fatal poisoning cases [11], and induces dopaminergic neuronal damage in experimental animals [4,18], indicating that this herbicide might cross the BBB. However, the possibility that this herbicide itself was responsible for neurotoxic events has been challenged, because the BBB penetration of paraquat has been controversial [23,25]. The BBB penetration of paraquat has not yet been supported by conclusive findings.…”

Immunohistochemical Studies on Paraquat-Induced Damage to Neuronal and Glial Cells in Rat Hippocampus.

“…Furthermore, this drug has been reported to be transported into glial cells [9]. It therefore seems conceivable that the metabolism of paraquat is prerequisite to its toxic effect on hippocampal neurons, and astrocytes may play a potential role in the expression of paraquat neurotoxicity as a putative site for metabolizing this drug.…”

“…Furthermore, this drug has also been shown to cause limbic motor seizures followed by pathological changes of hippocampal neurons in the rat brain [1,10], thereby suggesting that paraquat may cause oxidative damage to neuronal cells through the generation of radicals in the brain. However, paraquat has been shown to be transported into glial cells and capillary walls, but not localized in neurons [9]. Therefore, it seems possible that the neurotoxic effect of paraquat may be due to radicals generated in non-neuronal cells, but direct evidence for the involvement of these cells in the neuronal cell damage, particularly the oxidative damage to neurons, has not yet been elucidated.…”