EVALUATION OF THE ANTI-INFLAMMATORY ACTIVITY OF TEST
FORMULATIONS IN MOUSE MODEL OF PORCINE PANCREATIC ELASTASE-INDUCED EMPHYSEMA
1.0
TEST SYSTEM DETAILS:
Species : Mus musculus (Mice)
Strain : C57BL/6
Age :
6-8 weeks
Body Wight : 20- 25g
Sex : Male
No. of animals :
10 /Group: 6 animals for bronchoalveolar lavage and 4 animals for
histopathology
Total animals : 70
Study duration : 60 days
2.0
ALLOCATION OF GROUPS:
|
Group No. |
Group
Description |
Disease
Induction agent administered |
Treatment
administered |
Dose
Volume and Route |
|
G1 |
Normal Control |
Normal saline |
0.5% MC, p.o. |
10 ml/kg, p.o. |
|
G2 |
Disease Control |
50 μL (6.6 units/ mg) of elastase, once only |
0.5% MC, p.o. |
|
|
G3 |
Reference Control |
Roflumilast-10 mpk, q.d. in 0.5% MC |
||
|
G4 |
Treated with low dose of Test X1 |
Test X1
mg/kg, b.i.d. in 0.5% MC |
||
|
G5 |
Treated with intermediate dose 1 of Test X2 |
Test X2
mg/kg, b.i.d. in 0.5% MC |
||
|
G6 |
Treated with intermediate dose 2 of Test X3 |
Test X3
mg/kg, b.i.d. in 0.5% MC |
||
|
G7 |
Treated with high dose of Test X4 |
Test X4
mg/kg, b.i.d. in 0.5% MC |
X1, X2, X3, and X4 are defined as the incremental
doses of the Test formulations. MC-Methyl Cellulose, p.o.-per os. The dose
range will be from 10 mg/kg to 1000 mg/kg, q.d.: quaque die; bid: bis in die
3.0
METHOD:
- Healthy animals will be selected, randomized based on body weight and allocated into 7, different groups consisting of 10 animals each (6 animals for BALF collection and 4 animals for histopathology).
- Prophylactic dosing with test preparations will be initiated 7 days prior to induction.
- For induction, animals will be anaesthetized by ketamine (5 mg/kg) & xylazine (40 mg/kg). Subsequently, they will be held in a vertical position and 50 μL (6.6 units/ mg) of elastase will be administered on the edge of the nostril and inhaled by the mouse.
- Animals of the Group G1 will serve as normal control and administered 0.5% MC, p.o.
- Disease control (G2) animals will receive 0.5% MC, p.o.
- Animals of group G3 will be treated with reference drug Roflumilast 10 mg/kg, p.o.
- Animals of group G4-G7 will be treated with Test formulations (X1, X2, X3, and X4) at different dose levels for 28 days.
4.0 END POINT PARAMETER(S):
·
Evaluation of respiratory mechanics
·
Total and differential leukocyte counts in BALF
·
IL-1,
IL-6, IL-8 and IL-17 in BALF
·
Isoprostane (8-iso-PGF2)/ subunit p-65-NF-κB expression
· Histological analysis of lung tissue
5.0 REFERENCE(S):
1.
Games, E., Guerreiro, M.,
Santana, F.R., Pinheiro, N.M., De Oliveira, E.A., Lopes, F.D., Olivo, C.R.,
Tibério, I.F., Martins, M.A., Lago, J.H.G. and Prado, C.M., 2016. Structurally
related monoterpenes p-cymene, carvacrol and thymol isolated from essential oil
from leaves of Lippia sidoides Cham. (Verbenaceae) protect mice against
elastase-induced emphysema. Molecules, 21(10),
p.1390.
2.
Taguchi, L., Pinheiro,
N.M., Olivo, C.R., Choqueta-Toledo, A., Grecco, S.S., Lopes, F.D., Caperuto,
L.C., Martins, M.A., Tiberio, I.F., Câmara, N.O. and Lago, J.H.G., 2015. A
flavanone from Baccharis retusa (Asteraceae) prevents elastase-induced emphysema
in mice by regulating NF-κB, oxidative stress and metalloproteinases. Respiratory Research, 16(1),
pp.1-15.
3. Hamakawa, H., Bartolák-Suki, E., Parameswaran, H., Majumdar, A., Lutchen, K.R. and Suki, B., 2011. Structure–function relations in an elastase-induced mouse model of emphysema. American Journal of Respiratory Cell and Molecular Biology, 45(3), pp.517-524.
END OF THE DOCUMENT
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