Abstracts / Toxicology Letters 259S (2016) S73S247
at 3 and 45 days post NIL. All values were compared with their
control group. Also we blocked the V1a and V2 AVP receptors using
conivaptan and the MBP effects were measured.
Results: NIL caused signicant and permanent low AVP and
OT serum level (10.6 0.8 vs 2.4 0.16 (pg/ml) (SE), SHAM vs NIL
respectively), transient diabetes insipidus of 15 days of duration
and a signicant and permanent decrease of the MBP in 70% of the
NIL animals. Hypotension was apparent 30 min after NIL. No signif-
icant differences in the RAAS and serum electrolytes were evident,
whereas urine electrolytes were lower in NIL rats (Na; 33.08 6.177
vs 58.99 15.061 and K; 67.148 12.515 vs 126.9 26.97 respec-
tively). Conivaptan decreases the MBP in the 85% of the SHR treated
animals.
Conclusions: (1) The permanent deciency of AVP (NIL ani-
mals) is responsible of the low BP levels. (2) The normal Na and
K serum levels are due to the remnant basal concentrations of AVP.
(3) The NIL surgery and the AVP receptor blockers represent a novel
model for the study of homeostatic, cardiovascular and endocrine
mechanisms of essential hypertension.
http://dx.doi.org/10.1016/j.toxlet.2016.07.573
PO26.3
Erythrophagocytosis of lead-exposed
erythrocytes by renal tubular cells may
contribute to lead-induced nephrotoxicity
So-Youn Kwon, Jin-Ho Chung
College of Pharmacy, Seoul National University, Seoul, South Korea
Introduction: Nephrotoxicity associated with lead poisoning
has been frequently reported in epidemiological studies; but the
underlying mechanisms have not yet been fully elucidated.
Objective: We examined the role of erythrocytes, one of the
major bodily lead reservoirs, in lead-associated nephrotoxicity.
Methods and results: Co-incubation of lead-exposed eryth-
rocytes with renal proximal tubular cells (HK-2) signicantly
potentiated renal tubular cytotoxicity, reecting a role of eryth-
rocytes in lead-induced nephrotoxicity. Morphological and ow
cytometric analysis revealed that HK-2 actively phagocytized
lead-exposed erythrocytes, mediated by phosphatidylserine (PS)
externalization on erythrocyte membrane and generation of PS-
bearing microvesicles. Increased oxidative stress and expression
of nephrotoxic biomarkers such as NGAL or KIM-1 were observed
in HK-2 cells undergoing erythrophagocytosis. Moreover, TGF-,
a marker of brosis, was signicantly up-regulated in HK-2 cells
by erythrophagocytosis. The signicance of erythrophagocytosis in
lead-induced nephrotoxicity was examined in vivo in rats exposed
to lead via drinking water for 12 weeks. Increased iron depo-
sition and generation of oxidative stress in renal tissues were
found in lead-exposed rats, which matched well the histopatho-
logical alteration, brosis and expression of KIM-1, NGAL and
TGF-.
Conclusions: Our data strongly suggest that erythrophagocyto-
sis and iron deposition could signicantly enhance nephrotoxicity
following lead exposure, shedding a new light on the understanding
of lead-associated kidney damage.
http://dx.doi.org/10.1016/j.toxlet.2016.07.574
S239
PO26.4
Inammatory mediators produced by the
ocular surface after mycotoxin exposure impact
the nasal epithelium
S. Achard 1 , M. Bossou 1 , Y. Serssar 1 , J. Menotti 1 , I. Momas 1 , N.
Seta 1,2
1 Paris Descartes University, Faculty of Pharmacy of Paris, Public
Health Environment Laboratory (EA4064), Paris, France
2 Bichat Hospital, Biochemistry Laboratory, Paris, France
Background: Mycotoxin exposure is associated with asthma
and chronic airway inammation in farm workers after long-
term exposures with cereals or forages. However, if inhalation is
the main exposure pathway, exposure of biological contaminants
concerns also the ocular surface leading to irritations, underly-
ing phenomena to the allergic manifestations. These gateways
communicate between them by humoral or cellular exchanges
such as cytokines or dendritic cells respectively, and participate
to respiratory diseases exacerbation by increasing inammatory
responses.
Objective: In order to test the hypothesis that the eye takes part
in the occurrence of respiratory symptoms, we studied, using an
in vitro approach, the relationship between the eye and the nose for
the occurrence of respiratory symptoms, via inammatory markers.
Material and methods: Human corneal epithelial cells (HCE,
Episkin) and human reconstituted nasal epithelium (MucilAir,
Epithelix) were used. Mycotoxins tested were aatoxin B1 and
gliotoxin. To dene both concentration and exposure time allowing
to produce conditioned medium containing inammatory mark-
ers in the absence of toxicity, HCE cells were rst exposed to each
mycotoxin at different times and concentrations. Then, conditioned
media were brought into contact with MucilAir during 4 weeks. The
effects were assessed by viability tests (xCELLigence and MTT) and
cytokine production (IL-8).
Results: For each mycotoxin tested, a relationship dose- and
time-dependent was observed. The following conditions were con-
sidered to produce conditioned medium: aatoxin at 32 g/mL
and gliotoxin at 250 ng/mL for 48 h of exposure. The reconstructed
epithelium of nasal origin brought into contact with the condi-
tioned medium showed an increase in IL-8 production.
Conclusions: Our results reveal essential data on the interac-
tions that can exist between ocular and nasal routes of exposure.
These results may lead to strengthen our understanding of the
mechanisms leading to the occurrence of respiratory symptoms,
and to propose guidelines for personal protective equipment to be
used by exposed workers in the farming community.
http://dx.doi.org/10.1016/j.toxlet.2016.07.575