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Communications to the Editor |

High-Dose Dexfenfluramine May Cause Alveolitis and Pulmonary Fibrosis in Rats FREE TO VIEW

Oguzhan Yildiz, MD, PhD; Semih Senöz, MD; Cagatay Oktenli, MD
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Gülhane School of Medicine Ankara, Turkey

Correspondence to: Oguzhan Yildiz, MD, PhD, Department of Pharmacology, Gülhane School of Medicine, 06018-Etlik, Ankara, Turkey; e-mail: oyildiz@gata.edu.tr



Chest. 2000;118(2):568. doi:10.1378/chest.118.2.568
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To the Editor:

The use of fenfluramine derivatives is a well-established risk factor for primary pulmonary hypertension.12 Previously, we used dexfenfluramine (DF) to test its effects on glucose intake in rats.3Although, at the beginning, we did not plan to test its side effects, by the end of the study period we did observe some histopathologic tissue changes (unpublished observation). We read, with great interest, the fine article by Higenbottam et al4 on the acute effects of DF on human and porcine pulmonary vascular tone and resistance. Although we used high-dose and long-term DF treatment in rats, we now want to mention about our observations, as the histopathologic changes may be related to pulmonary hypertension. In our study,3 we used 10 adult male Wistar albino rats (100 to 150 g), divided into two groups. DF (10 mg/kg/d) was given orally by gavage to the first group (n = 5) for 30 days. During this period, the second (control) group (n = 5) received equivalent volumes of saline orally. The weight gain was recorded weekly. DF prevented weight gain throughout the study (p < 0.05 vs control group). On the 31st day, the rats were killed by cervical dislocation. Lungs, testicles, kidneys, and retroperitoneal tissues (iliopsoas muscle and abdominal aorta) were examined macroscopically and histologically. No particular changes in testicular, renal, or retroperitoneal tissue morphology were observed in the animals treated with DF compared with the animals in the control group. However, while the lungs of the control group animals were morphologically normal, peribronchial diffuse lymphoid infiltration and dense hemorrhagic areas were seen in all alveolar regions of the lungs in the animals treated with DF. Interstitial lung disease and pleural and retroperitoneal fibrosis through serotonergic drugs had been previously reported.12,5 However, there is no report as to whether DF causes tissue fibrosis. In conclusion, high-dose and long-term use of DF may cause alveolitis, which may further lead to pulmonary fibrosis in rats.

References

Simonneau, G, Eartoukh, M, Sitbon, O, et al (1998) Primary pulmonary hypertension associated with the use of fenfluramine derivatives.Chest114,1958-1998
 
Vivero, LF, Anderson, PO, Clark, RF A close look at fenfluramine and dexfenfluramine.J Emerg Med1998;16,197-205. [CrossRef] [PubMed]
 
Yildiz, O, Bolu, E, Deniz, G, et al Effects of dexfenfluramine on glucose drinking and glucose-conditioned flavour preferences in rats: taste versus post-ingestive conditioning.Pharmacol Res1996;33,41-46. [CrossRef] [PubMed]
 
Higenbottam, T, Marriott, H, Cremona, G, et al The acute effects of dexfenfluramine on human and porcine pulmonary vascular tone and resistance.Chest1999;116,921-930. [CrossRef] [PubMed]
 
Gelford, GJ, Cromwell, DK Methysergide, retroperitoneal fibrosis, and rectosigmoid stricture.AJR Am J Roentgenol1968;104,566-570
 

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References

Simonneau, G, Eartoukh, M, Sitbon, O, et al (1998) Primary pulmonary hypertension associated with the use of fenfluramine derivatives.Chest114,1958-1998
 
Vivero, LF, Anderson, PO, Clark, RF A close look at fenfluramine and dexfenfluramine.J Emerg Med1998;16,197-205. [CrossRef] [PubMed]
 
Yildiz, O, Bolu, E, Deniz, G, et al Effects of dexfenfluramine on glucose drinking and glucose-conditioned flavour preferences in rats: taste versus post-ingestive conditioning.Pharmacol Res1996;33,41-46. [CrossRef] [PubMed]
 
Higenbottam, T, Marriott, H, Cremona, G, et al The acute effects of dexfenfluramine on human and porcine pulmonary vascular tone and resistance.Chest1999;116,921-930. [CrossRef] [PubMed]
 
Gelford, GJ, Cromwell, DK Methysergide, retroperitoneal fibrosis, and rectosigmoid stricture.AJR Am J Roentgenol1968;104,566-570
 
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