Prenatal exposure to a non-steroidal anti-inflammatory drug or saline solution impairs sciatic nerve morphology: a stereological and histological study.
The toxic effect of non-steroidal anti-inflammatory drugs (NSAIDs) during development has been widely investigated. While it has been shown that these drugs impair central nervous development and compromise the neural activity, the effects of these substances on the development of peripheral nerves are still not clarified. In the present study, sciatic nerves withdrawn from three experimental groups of 4-week-old rats, prenatally exposed to either saline solution, or diclofenac sodium, and controls not exposed to any substance, were evaluated in terms of axon number, cross-sectional area of axon and myelin sheet thickness as well as of the ultrastructure of nerve fibers. Comparisons of stereological estimations among these three groups showed that axon number and mean axon cross-sectional area, but not average myelin sheet thickness, were significantly decreased in rats that were exposed to both diclofenac sodium and also to the saline solution, in comparison of the control group. Electron microscope analysis revealed, in both treated groups, deterioration of myelin sheaths that was more pronounced in rats that were exposed to diclofenac sodium. Altogether, these findings show that the prenatal administration of both diclofenac sodium and saline solution impairs peripheral nervous system development, thus suggesting that this potential teratogenic effect should be also taken into consideration in the clinical use of these substances in pregnant patients.
Canan
Sinan
S
Department of Physiology, Baskent University School of Medicine, TR-06530 Ankara, Turkey. sinancanan@gmail.com
Aktaş
Abit
A
Ulkay
M Basak
MB
Colakoglu
Serdar
S
Ragbetli
Murat Cetin
MC
Ayyildiz
Mustafa
M
Geuna
Stefano
S
Kaplan
Suleyman
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D048429:Cell Size / Q000187:drug effects; D004008:Diclofenac / Q000633:toxicity; D005260:Female; D019044:Image Cytometry; D008297:Male; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology; D009421:Nervous System Malformations / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D012584:Sciatic Nerve / Q000002:abnormalities* / Q000187:drug effects* / Q000503:physiopathology; D012965:Sodium Chloride / Q000633:toxicity; D013723:Teratogens / Q000633:toxicity; D014855:Wallerian Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013723:Teratogens; D004008:Diclofenac; D012965:Sodium Chloride