Marjoram Oil Attenuates Valproic Acid-Induced Pancreatic Damage in Adult Male Albino Rats: A Histological and Immunohistochemical Study

Abstract

Background: Valproic acid [VA] is an antiepileptic drug that is extensively prescribed for many neurological disorders. Its use is associated with serious pancreatic complications. Marjoram oil [MO] is a health protective agent with proved anti-oxidant activity.Aim: Study of the effect of valproic acid on pancreas of adult male albino rats exploring novel mechanisms of VA-induced pancreatic damage and to evaluate the potential protective role of marjoram oil. Materials and Methods: Fifty adult male albino rats were used as a control group, a valproic acid group and a valproic acid-marjoram group. Both VA [200mg/kg] and MO [0.5ml/kg] were given once a day orally for eight weeks. Specimens of the pancreas were processed for light and electron microscopic studies. Immunohistochemical study was performed using anti-P53 antibodies. Results: Specimens of the valproic acid group showed an obvious distortion in the pancreatic acini as well as the islets of Langerhans. The acinar and islets cells showed cytoplasmic vacuoles and pyknotic nuclei. Large autophagic vacuoles containing an acidophilic material appeared in many cells. Dilated ducts and blood vessels were seen. There was a significant increase in the P53-immunoreaction of the acinar and islets cells and a significant decrease in the number of the zymogen granules of the acinar cells. Ultrastructurally, there were shrunken nuclei with irregularity, dilated rough endoplasmic reticulum and swollen mitochondria in the acinar cells and beta cells. In contrast, minimal changes occurred in the valproic acid-marjoram group that received MO before VA. Conclusion: Valproic acid administration to albino rats resulted in significant structural alterations in the pancreas. Marjoram oil attenuated VA effect and preserved the pancreas structure.