title: A Mechanistic Study on the Amiodarone-Induced Pulmonary Toxicity.
abstract: Amiodarone- (AM-) induced pulmonary toxicity (AIPT) is still a matter of research and is poorly understood. In attempting to resolve this issue, we treated Sprague-Dawley rats with AM doses of 80 mg/kg/day/i.p. for one, two, three, and four weeks. The rats were weighed at days 7, 14, 21, and 28 and bronchoalveolar lavages (BAL) were obtained to determine total leukocyte count (TLC). For each group, lung weighing, histopathology, and homogenization were performed. Fresh homogenates were used for determination of ATP content, lipid peroxides, GSH, catalase, SOD, GPx, GR activities, NO, and hydroxyproline levels. The results showed a significant decrease in body weight and GSH depletion together with an increase in both lung weight and lung/body weight coefficient in the first week. Considerable increases in lung hydroxyproline level with some histopathological alterations were apparent. Treatment for two weeks produced a significant increase in BAL fluid, TLC, GR activity, and NO level in lung homogenate. The loss of cellular ATP and inhibition of most antioxidative protective enzymatic system appeared along with alteration in SOD activity following daily treatment for three weeks, while, in rats treated with AM for four weeks, more severe toxicity was apparent. Histopathological diagnosis was mostly granulomatous inflammation and interstitial pneumonitis in rats treated for three and four weeks, respectively. As shown, it is obvious that slow oedema formation is the only initiating factor of AIPT; all other mechanisms may occur as a consequence.
authors.affiliation: Saudi Food and Drug Authority, AlKhaleej District, Prince Bander Street, P.O. Box 376067, Riyadh 11335, Saudi Arabia.
authors.forename: Bader
authors.initials: B
authors.lastname: Al-Shammari
authors.affiliation: Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Khalifa
authors.affiliation: Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Bakheet
authors.affiliation: Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Moustafa
authors.initials: M
authors.lastname: Yasser
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000638:Amiodarone / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D017207:Rats, Sprague-Dawley
chemical_list: D009569:Nitric Oxide; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D005978:Glutathione; D000638:Amiodarone; D006909:Hydroxyproline