Asia Pac Allergy.  2011 Oct;1(3):138-144. 10.5415/apallergy.2011.1.3.138.

Investigation of the antiallergic activity of olopatadine on rhinitis induced by intranasal instillation of antigen in sensitized rats using thermography

Affiliations
  • 1Pharmacological Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., Shizuoka 411-8731, Japan. tadafumi.tamura@kyowa-kirin.co.jp

Abstract

BACKGROUND
The main symptoms of allergic rhinitis (AR) are sneezing, rhinorrhea and nasal obstruction. It was reported that the nasal skin temperature after intranasal administration of histamine or grass pollen rose. In patients with AR, the levels of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) have increased in nasal fluids and mucosa.
OBJECTIVE
The present study were to determine the temperature changes of the nose in rat allergic rhinitis model, and if olopatadine, an antiallergic agent with histamine H1 receptor antagonistic action, proved to be effective, were studied the productions of NGF and VEGF in nasal lavage fluids (NALF). In the present study, we used ovalbumin (OVA)-sensitized rats as an animal model of nasal allergy and examined the effects of olopatadine on the skin temperature of the nose area, and the productions of NGF and VEGF in NALF.
METHODS
The temperature changes of the nose area were carried out with thermo tracer in rat passively sensitized with OVA antiserum. The numbers of sneezing episodes were counted and, NGF and VEGF levels in NALF were examined using the specific ELISA.
RESULTS
In OVA-sensitized rats, the number of sneezing episodes increase and the nasal skin temperature rise were provoked after OVA challenge. The levels of NGF and VEGF in NALF also were increased. Olopatadine reduced the increased frequency of sneezing and the nasal skin temperature rise. It also inhibited the increased NGF and VEGF productions in NALF.
CONCLUSION
The nasal skin temperature after OVA challenge rose even in OVA-sensitized rats. These results suggest that the suppression of the increased NGF and VEGF levels might partially be involved in the improvement of allergy-like behavior (sneezing and nasal skin temperature rise) by the treatment of olopatadine.

Keyword

Olopatadine; Antihistamine; Animal model; Rhinitis; Thermography

MeSH Terms

Administration, Intranasal
Animals
Enzyme-Linked Immunosorbent Assay
Histamine
Humans
Hypersensitivity
Models, Animal
Mucous Membrane
Nasal Lavage Fluid
Nasal Obstruction
Nerve Growth Factor
Nose
Olopatadine Hydrochloride*
Ovalbumin
Ovum
Poaceae
Pollen
Rats*
Receptors, Histamine H1
Rhinitis*
Rhinitis, Allergic
Skin Temperature
Sneezing
Thermography*
Vascular Endothelial Growth Factor A
Histamine
Nerve Growth Factor
Olopatadine Hydrochloride
Ovalbumin
Receptors, Histamine H1
Vascular Endothelial Growth Factor A

Figure

  • Fig. 1 Protocol for ovalbumin (OVA) sensitization and challenge. OVA was prepared at 400 µg/mL in physiological saline and precipitated at 1:1 ratio with Al(OH)3 (20 mg/mL). Rats were sensitized by intraperitoneal injections of 200 µg OVA (1 mL OVA-Al(OH)3 suspension) on Days 1, 2, 3 and 11. Bordetella (B.) pertussis (1010 organisms in physiological saline) were injected into the four footpads on Day 1. Rats were challenged with OVA in physiological saline (100 mg/mL, 25 µL × 2) into the bilateral nasal cavities using a micropipette for 2 or 4 consecutive days. Drugs were orally administered 1 h before each OVA challenge. NALF: nasal lavage fluids.

  • Fig. 2 Nasal skin temperature change after the last nasal ovalbumin (OVA) challenge. The images of thermograph were at 1 h after the OVA challenge. The temperature is color coded. A change from blue to red indicates an increase in temperature. Olopatadine was orally administered 1 h before the OVA challenge.

  • Fig. 3 Nasal skin temperature change after the last nasal ovalbumin (OVA) challenge. Maximum (A) and mean (B) temperature change. Olopatadine and prednisolone were orally administered 1 h before the OVA challenge. The nasal skin temperature was measured at 0.25, 0.5, 1, 2, 3, 4 and 6 h after the OVA challenge. □: saline, ●: OVA challenge, □: olopatadine, ■: prednisolone. Each point represents the mean ± SE of 6 rats. †p < 0.05, ††p < 0.01, †††p < 0.001: significantly different from the OVA challenged group.

  • Fig. 4 Effects of olopatadine and prednisolone on the number of sneezing induced by the ovalbumin (OVA) challenge. Olopatadine and prednisolone were orally administered before the OVA challenge. The number of sneezing was measured for 10 min. Each column represents the mean ± SE of 7 rats. Saline: physiological saline challenge, OVA: OVA challenged control. †††p < 0.001: significantly different from the OVA challenged group (Student's t-test). ‡‡‡p < 0.001: significantly different from the OVA challenged group (Aspin-Welch test). **p < 0.01, ***p < 0.001: significantly different from the OVA challenged group (Dunnett test).

  • Fig. 5 Effects of olopatadine and prednisolone on the production of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) in the nasal lavage fluids (NALF) induced by the ovalbumin (OVA) challenge. NGF (A) and VEGF (B) levels in the NALF were measured 6 h after OVA challenge. Each column represents the mean ± SE of 6-7 rats. *p < 0.05: significantly different from the OVA challenged group (Dunnett test). †p < 0.05: significantly different from the OVA challenged group (Student's t-test). ‡p < 0.05: significantly different from the OVA challenged group (Aspin-Welch test).


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