SAFRANAL AMELIORATES SODIUM VALPROATE-INDUCED LIVER TOXICITY IN RATS BY TARGETING GENE EXPRESSION, OXIDATIVE STRESS AND APOPTOSIS.

  • Alaaeldin A. Hamza1*, Fawkya El hodairy2 AymanM. Badawi3 1*Hormone Evaluation Department, National Organization for Drug Control and Research [NODCAR], Giza, Egypt 2Physiology Department, National Organization for Drug Control and Research, Giza, Egypt 3Biochemistry Department, National Organization for Drug Control and Research, Giza, Egypt

Abstract

Sodium valproate (VPA) is a potentially hepatotoxic antiepileptic drug. Safranal(SAF), an essential oil derived from saffron, possesses a potent antioxidant, anti-apoptotic and anticancer properties. The current study aimed to investigate the protective effect and underlying mechanisms of SAF on the hepatotoxicity induced by VPA. SAF at the dose of 25 mg/kg was orally administered prior to VPA treatment (500 mg/kg) to rats once daily for 14 consecutive days. SAF treatment attenuated VPA-induced liver dysfunction, structural damage, hepatic ATP depletion and reduction in total antioxidant content. Moreover, SAF attenuated VPA-induced elevation in hepatic oxidant contents and lipid peroxidation. These effects were accompanied by a significant increase in gene expression of carnitine palmitoyltransferase 1A, fibroblast growth factor 21, peroxisome proliferator-activated receptor gamma 1, cytochrome P450 2E1 (CYP2E1) and heme oxygenase 1. SAF combat these effects especially in the group of rats treated VPA plus SAF. Furthermore, VPA provoked apoptotic responses evidenced by increasing protein expression of Bax and caspases-3. SAF pretreatment significantly ameliorated these apoptotic signals indicating its anti-apoptotic actions. SAF attenuates VPA-induced liver injury through decreasing the expression CYP2E1 with consequently, alleviation of oxidative stress and apoptotic signals as well as depletions of ATP. Keywords: Liver damage, Safranal, Sodium valproate, Oxidative stress, Apoptosis.

Published
2017-10-30
How to Cite
AymanM. Badawi3A. A. H. F. E. hodairy2. (2017). SAFRANAL AMELIORATES SODIUM VALPROATE-INDUCED LIVER TOXICITY IN RATS BY TARGETING GENE EXPRESSION, OXIDATIVE STRESS AND APOPTOSIS. Journal of Biomedical and Pharmaceutical Research, 4(6). Retrieved from https://jbpr.in/index.php/jbpr/article/view/235
Section
Research Articles