Retroperitoneal fibrosis

To the Editor:

The use of fenfluramine derivatives is a well-established risk factor for primary pulmonary hypertension.[1,2] Previously, we used dexfenfluramine (DF) to test its effects on glucose intake in rats.[3] Although, 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not plan to test its side effects, by the end of the study period we did observe some histopathologic tissue changes (unpublished observation).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 al[4] 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 garage 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 [is less than] 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.[1,2,5] 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.

Oguzhan Yildiz, MD, PhD Semih Senoz, MD Cagatay Oktenli, MD Gulhane School of Medicine Ankara, Turkey

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

REFERENCES

[1] Simonneau G, Eartoukh M, Sitbon O, et al. Primary pulmonary hypertension associated with the use of fenfluramine derivatives. Chest 1998; 114:1958-1998

[2] Vivero LF, Anderson PO, Clark RF. A close look at fenfluramine and dexfenfluramine. J Emerg Med 1998; 16:197-205

[3] 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 Res 1996; 33:41-46

[4] Higenbottam T, Marriott H, Cremona G, et al. The acute effects of dexfenfluramine on human and porcine pulmonary vascular tone and resistance. Chest 1999; 116:921-930

[5] Gelford GJ, Cromwell DK. Methysergide, retroperitoneal fibrosis, and rectosigmoid stricture. AJR Am J Roentgenol 1968; 104:566-570

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