Prenatal exposure to a non‐steroidal anti‐inflammatory drug or saline solution impairs sciatic nerve morphology: a stereological and histological study

Abstract

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 In the present study, sciatic nerves withdrawn from three experimental groups of 4-week-old rats, prenatally exposed to either saline solution, or diclofenac sodium, and controls not exposed to any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.

Effects of prenatally exposed diclofenac sodium on rat heart tissue:a stereological and histological study

“…The results showed that this drug decreases the number of cells. Similar results of the side effects of prenatal exposure to DS on the central and peripheral nervous tissues were also found by our group (4)(5)(6). On the other hand, even prenatal exposure of DS increased total Purkinje cell number in the female rats (37), but no significant differences were found between the granular cell numbers of male juvenile and adult rats exposed to DS prenatally (38).…”

Original article Prenatal exposure of diclofenac sodium affects morphology but not axon number of the median nerve of rats

“…Few of these mention the morphological and/or developmental characteristics of these nerves. The neurotoxic effects of DS on the sciatic nerve were investigated in rats exposed to DS during the gestational period [5], and a substantial axon loss was found in the nerve in DS-exposed groups. In contrast, in the present study, no significant difference was found regarding axon number among the control, saline, and DS groups, which included both male and female rats (p > 0.05).…”

“…We previously re ported a toxic effect of DS on sciatic nerve, pyramidal and granular cells of hippocampus, and Purkinje cells of male rats but not female rats following prenatal exposure [5,10,16,19]. These studies showed that the toxic ef fects of prenatal exposure to DS are gender dependent.…”

The Axon Number of the Rat Sciatic Nerve: A Stereological Study

“…A manual stereological workstation composed of a digital camera (Nikon COOLPX5400, Tokyo, Japan) a manual dial indicator controlled specimen stage and a light microscope (Nikon Microphot-FX Tokyo. Japan) was used for axon number counting [10] . To obtain an estimation of total myelinated axon number in an unbiased manner the axon profiles in the nerve cross-section are sampled with equal probability regardless of shape size orientation and location that means each sampled item was selected with a systematic random manner [11] .…”