Uptake of Inorganic Mercury in the Olfactory Bulbs via Olfactory Pathways in Rats

Henriksson, Jörgen; Tjälve, Hans

doi:10.1006/enrs.1997.3817

Cited by 66 publications

(31 citation statements)

References 23 publications

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“…To date, lot of work has been reported for brain targeting using intanasal route (Mathison et al, 1998;Stevens et al, 2011). Few of them include nerve growth factor (Chou & Donovan, 1998), inorganic mercury (Henriksson & Tjalve, 1998), dihydroergotamine (Wang et al, 1998), taurine (Brittebo & Eriksson, 1995), carboxylic acids (Eriksson et al, 1999), 2 0 ,3 0 -didehydro-3 0 -deoxythymidine (Yajima et al, 1998) and many high molecular weight peptides (Frey et al, 1997) bagged in INDD. Kumar et al (1982) who showed that progesterone (MW 314.46 Da) achieved a higher distribution in the CSF than in the blood after intranasal administration.…”

Section: Introductionmentioning

confidence: 99%

Brain targeting by intranasal drug delivery (INDD): a combined effect of trans-neural and para-neuronal pathway

et al. 2014

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The effectiveness of intranasal drug delivery for brain targeting has emerged as a hope of remedy for various CNS disorders. The nose to brain absorption of therapeutic molecules claims two effective pathways, which include trans-neuronal for immediate action and para-neuronal for delayed action. To evaluate the contribution of both the pathways in absorption of therapeutic molecules and nanocarriers, lidocaine, a nerve-blocking agent, was used to impair the action potential of olfactory nerve. An anti-Parkinson drug ropinirole was covalently complexes with 99m Tc in presence of SnCl 2 using in-house developed reduction technology. The radiolabeled formulations were administered intranasally in lidocaine challenged rabbit and rat. The qualitative and quantitative outcomes of neural and non-neural pathways were estimated using gamma scintigraphy and UHPLC-MS/MS, respectively. The results showed a significant (p 0.005) increase in radioactivity counts and drug concentration in the brain of rabbit and rat compared to the animal groups challenged with lidocaine. This concludes the significant contribution (p 0.005) of trans-neuronal and para-neuronal pathway in nose to brain drug delivery. Therefore, results proved that it is an art of a formulator scientist to make the drug carriers to exploit the choice of absorption pathway for their instant and extent of action.

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Section: Introductionmentioning

confidence: 99%

Brain targeting by intranasal drug delivery (INDD): a combined effect of trans-neural and para-neuronal pathway

et al. 2014

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“…That is true for some metals like Al, Cd, Co, Hg, Mn, Ni, and Zn (Henriksson et al, 1998;Tjälve et al, 1999;Tjälve et al, 1996) (and see Sunderman, 2001 for review), viruses (Huneycutt et al, 1994;Schultz et al, 1937), and ultrafine particles (Oberdörster et al, 2004), and also for dopamine (Dahlin et al, 2001) or morphine (Westin et al, 2006). Cadmium (Cd) is a heavy metal having important environmental and occupational concerns.…”

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confidence: 96%

Harmful Effects of Cadmium on Olfactory System in Mice

Bondier

Michel

Propper

et al. 2008

Inhalation Toxicology

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The inhalation of certain metals can result in olfactory epithelial injury, an altered sense of smell, and direct delivery of the metal from the olfactory epithelium to the olfactory bulbs and other parts of the central nervous system. The purpose of this study was to examine whether mice given an intranasal instillation of cadmium would develop altered olfactory function and to assess whether cadmium may be transported directly from the olfactory epithelium to the central nervous system. To evaluate cadmium's ability to induce anosmia and on the basis of olfactory epithelium sensitivity to metals, the aim of this study was first to study cadmium effects on the olfactory function and secondly to check whether cadmium may be transported from the nasal area to the central nervous system. After an intranasal instillation of a solution containing CdCl 2 at 136 mM, we observed in treated mice: (1) a partial destruction of the olfactory epithelium, which is reduced to three or four basal cell layers followed by a progressive regeneration; (2) a loss of odor discrimination with a subsequent recovery; and (3) a cadmium uptake by olfactory bulbs demonstrated using atomic absorption spectrophotometry, but not by other parts of the central nervous system. Cadmium was delivered to the olfactory bulbs, most likely along the olfactory nerve, thereby bypassing the intact blood-brain barrier. We consider that cadmium can penetrate olfactory epithelium and hence be transported to olfactory bulbs. The olfactory route could therefore be a likely way to reach the brain and should be taken into account for occupational risk assessments for this metal.

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“…To our knowledge, a possible efflux of organic and inorganic mercury species out of the brain side has yet not been evaluated. Although inorganic Hg does not seem to be able to cross the blood-brain barrier [32], it is present in the brain due to dealkylation of organic species or an oxidation of elemental Hg [18, 21]. Thus, the elucidation of an efflux of inorganic Hg besides the organic compounds is of special interest.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, because of a possible dealkylation of the organic compounds as well as an oxidation of elemental Hg, e.g. resulting from the outgassing of amalgam fillings, inorganic Hg has to be taken into account, when investigating mechanisms of Hg species dependent transfer into/out of the brain and Hg species induced neurotoxicity [20, 21]. Toimela et al demonstrated transfer differences between mercury chloride (HgCl 2 ) and methylmercury chloride (MeHgCl) within an in vitro blood-brain barrier model composed of rat brain endothelial cells accompanied with glia cells and neuronal SH-SY5Y cells as target cells [22].…”

Section: Introductionmentioning

confidence: 99%

Effects on and transfer across the blood-brain barrier in vitro—Comparison of organic and inorganic mercury species

Lohren

Bornhorst

Fitkau

et al. 2016

BMC Pharmacol Toxicol

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BackgroundTransport of methylmercury (MeHg) across the blood-brain barrier towards the brain side is well discussed in literature, while ethylmercury (EtHg) and inorganic mercury are not adequately characterized regarding their entry into the brain. Studies investigating a possible efflux out of the brain are not described to our knowledge.MethodsThis study compares, for the first time, effects of organic methylmercury chloride (MeHgCl), EtHg-containing thiomersal and inorganic Hg chloride (HgCl2) on as well as their transfer across a primary porcine in vitro model of the blood-brain barrier.ResultsWith respect to the barrier integrity, the barrier model exhibited a much higher sensitivity towards HgCl2 following basolateral incubation (brain-facing side) as compared to apical application (blood-facing side). These HgCl2 induced effects on the barrier integrity after brain side incubation are comparable to that of the organic species, although MeHgCl and thiomersal exerted much higher cytotoxic effects in the barrier building cells. Hg transfer rates following exposure to organic species in both directions argue for diffusion as transfer mechanism. Inorganic Hg application surprisingly resulted in a Hg transfer out of the brain-facing compartment.ConclusionsIn case of MeHgCl and thiomersal incubation, mercury crossed the barrier in both directions, with a slight accumulation in the basolateral, brain-facing compartment, after simultaneous incubation in both compartments. For HgCl2, our data provide first evidence that the blood-brain barrier transfers mercury out of the brain.

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Uptake of Inorganic Mercury in the Olfactory Bulbs via Olfactory Pathways in Rats

Cited by 66 publications

References 23 publications

Brain targeting by intranasal drug delivery (INDD): a combined effect of trans-neural and para-neuronal pathway

Brain targeting by intranasal drug delivery (INDD): a combined effect of trans-neural and para-neuronal pathway

Harmful Effects of Cadmium on Olfactory System in Mice

Effects on and transfer across the blood-brain barrier in vitro—Comparison of organic and inorganic mercury species

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