Carisoprodol (Somadril) induced histological and histochemical changes in renal cortex of pregnant rats and their fetuses

Abstract

Background: Carisoprodol is a generally prescribed skeletal muscle relaxant whose primary active metabolite is meprobamate, a substance with well-established abuse potential similar to that of benzodiazepines. A number of reports showed that carisoprodol has been abused for its anodyne and relaxant effects. Aim: The diversion and misuse of carisoprodol and its adverse health effects appeared to be dramatically increased over the last several years. This study aimed to detect the histological and histochemical changes in the cortex of renal tissue of pregnant rats and their fetuses after treatment with carisoprodol. Materials and Methods: Thirty pregnant female rats were randomly categorized into three groups (ten pregnant female rats in each group). The first was administered oral doses of distilled water and served as control. The other two groups were administered oral doses of carisoprodol (Somadril compound) in the distilled water equivalent to 10.8 and 21.6 mg/100g body weight/day respectively for 15 days from the 6 th day to the 20 th day of gestation. Results: Maternal and fetal renal cortex tissue of both treated groups showed lots of degenerative changes post-treatment with carisoprodol. The severity of these changes was more obvious in fetal cortex of renal tissue of both groups this was accompanied with numerous histochemical changes. Conclusion: Treatment of pregnant rats with carisoprodol led to numerous dystrophic changes in the maternal and fetal renal cortex tissue. These findings provide evidence to support current recommendations to avoid the use of carisoprodol in pregnant rats except if the potential benefit justifies the risk to the fetuses.

Histological, Histochemical and Immunohistochemical Alterations Induced in Rat’s fetalskeletal Muscle Fibres and Skin Intoxicated Maternally with

“…In the present study, amyloid-beta protein increased in the fetal skeletal muscles in S1 and S2 sets compared to the control set.These results agree with those of Abdelhafez and AbdRabou (20) who found increased amyloid-beta protein in the liver tissue of the fetal rat maternally treated with carisoprodol.The same authors added that amyloids are insoluble fibrous protein and they result from polypeptides and nearly 18 unsuitably folded forms of protein that present normally in the body.These misfolded constructions alter their good configuration and they erroneously interact with each other or other cell components forming insoluble amyloid fibers.Also, the present results agree with the study of AbdRabou and Alotibi (34) who found an increase in amyloid-beta protein in the fetal ileum tissues of the pregnant rat treated with carisoprodol. The same authors stated that the abnormal accretion of amyloidbeta protein in the tissues may play an important function in numerous neurodegenerative syndrome and cause amyloidosis.…”

“…In this work highly increased collagen fibres was detected in the epidermal and dermal layers especially hair follicles, hemorrhage and dilated capillaries were also observed in the treated fetal groups S1 and S2 compared to the control fetal groups. This investigation agrees with those of Abdelhafez and AbdRabou (20) who treated rats with somadril and they noticed highly increased collagen fibres in the renal tissues of pregnant rats of group S1 and S2 especially in the brush borders and basement membranes of the convoluted tubules.…”

“…In the liver, carisprodol is metabolized to meprobamate ( the primary active metabolites) which is excreted via the renal and non-renal pathways. In the pregnant rat, carisoprodol can cross the placenta (20) and congenital abnormalities were occurred (9) .The same author added that carisoprodol was excreted in breast milk at concentrations two to four times that in maternal plasma.skin is probably the path for excretion of risky substances occurred in the environment.skin is one of the pathways for removing risky substances occurred in the environment. Also, the skin is considered as a mirror for the internal body and its healthy look gives a good idea about the state of the organs (30) .In the present work, fetuses of mothers treated with carisoprodol showed many alterations in the skin of groups S1 and S2 compared to the control group.…”

“…Normally, collagen is essential for formation of muscles, skin, ligaments and blood vessels.The increased collagen may lead to an increase in the defense reaction against toxic materials (31) . Increased collagen deposition may be due to encourage of expression of genes involved in collagen biosynthesis due to oxidative stress (9,20) . Results of the current study revealed an increase of polysaccharides in the fetal skeletal muscle fibres of S1 and S2 groups in a dose-dependent manner as compared to the control group.…”