Paper Information

Title: 

INVESTIGATION OF PENICILLAMINE EFFECTS ON BLEOMYCIN INDUCED PULMONARY FIBROSIS IN RATS

Type: POSTER
Author(s): VAEZ A.*,MIKAEILI P.,AJOUDANI T.,MAHMOUDIFAR F.,SHAYEGH JALAL,HEMATI A.A.,FARAHMANDIAN EHSAN
 
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Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2009Volume 19
 
 
Abstract: 

Penicillamine is indicated in the treatment of Wilson’s disease, a copper poisoning inherited condition. Wilson’sDisease Treatment has two objectives: (1) To minimize dietary intake and absorption of copper. (2) To promote excretion of copper deposited in tissues. For the second objective Penicillamine is the only copper chelating agent that is orally effective. In this study, we have tried a copper-decreasing therapy (Penicillamine) to verify whether it inhibits development of pulmonary fibrosis in the bleomycin mouse model or not. We have also considered a low price of this drug, which is routinely used as a toxicity antidote in the clinical practices, in comparison with other similar agents. Male Sprague-Dawley rats (n=30), received an intratracheal (IT) injection of bleomycin (7.5 IU/kg) in saline solution for induction of pulmonary fibrosis. The animals were divided into the following groups (n=6): Group 1 received only a single-dose bleomycin (7.5IU/kg, IT) as “positive control”. The rats in group 2 received vehicle (normal saline, IT) as “negative control”. Group 3 or “Treatment-P1 group” received daily penicillamine 50mg/kg/day intraperitoneally (IP), 7 days before and 4 weeks after administering a singledose bleomycin (7.5IU/ kg, IT). Group 4 or “Treatment-P2 group” received daily penicillamine 300mg/kg/day (IP), 7 days before and four weeks after administering a single dose bleomycin (7.5 IU/kg, IT). We also investigated the effects of the drugs and the vehicle (without bleomycin) as sham groups and group 5 penicillamine 300mg/kg/day (IP) plus the vehicle (IT) for five weeks as “sham P”. All the ethical issues were considered throughout the experiment based on the Urmia Medical University Ethical Protocols (UMUEP) on animal experiments. The cytokines (IL-8, TNF-a, TGF-b1) through ELISA kits, the amount of collagen in the lungs (hydroxyproline content), and pharmacological activity of the lung strip tissues were determined. Histological investigation of lung tissue showed that rats of group 3 and 4 had less pathological changes in lung tissues as compared to group 1 (p<0.05). The severity of changes in lung tissues is less in group 4 as compared with group 3 (p<0.05). The studies on contractility of lung-tissue strips showed that rats of group 3 and 4 had fewer contractions of lung strip preparations as compared to group 1. The amount of contractions of lung strip preparations is less in group 4 as compared with group 3. The study of collagen and hydroxyproline content of lung tissue revealed that rats of group 3 (P1: penicillamine 50mg/kg/day) and group 4 (P2: penicillamine 300mg/kg/day) had less hydroxyproline content of lung as compared to group one. The amount of lung hydroxyproline content is less in group 4 as compared with group 3. Evaluating the cytokine profile in the studied groups suggested that rats in group 3 and 4 had less amounts of fibrogenic cytokines as compared to group 1. The cytokine levels have been decreased in the treated groups receiving 50 and 300 mg/kg/day penicillamine, in comparison to positive control group (p<0.05 and p<0.01, respectfully). Taken together, there were no other similar works in the literature about the effects of penicillamine on the lung tissue in the lung fibrosis, induced by bleomycin, this agent is suggested in our study for the first time as "a potential protective agent" for pulmonary fibrosis. Penicillamine may have a protective effect against bleomycin induced pulmonary fibrosis as evidenced by the reduction of the severity of lung tissue changes, collagen amounts and cytokines levels caused by bleomycin in rat lung tissues.

 
Keyword(s): PULMONARY FIBROSIS, BLEOMYCIN, PENICILLAMINE, CYTOKINES
 
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