Rutin Protects from Destruction by Interrupting the Pathways Playing a Role in the Possible Damage Mechanism of Sodium Valproate in the Liver and Kidney Tissues of Rats

Abstract

Background: The present study investigated the effects of rutin (RUT), which has various biological and pharmacological properties, on liver and kidney damage caused by histone deacetylase inhibitor valproic acid (VLP), which is used in the treatment of many psychiatric disorders.Methods and Results: In the study, 50 or 100 mg/kg RUT treatment was administered 30 minutes after 500 mg/kg VLP was given to rats for 14 days. Then, some pathways that may be involved in the damage mechanism of VLP in liver and kidney tissues were investigated using biochemical, RT-PCR and Western blotting techniques. The results show that the levels of MDA induced by VLP in liver and kidney tissues decreased after RUT treatment, and the levels of SOD, CAT, GPx and GSH suppressed by VLP increased after RUT administration. It was observed that ER stress induced by oxidative stress was alleviated by suppressing the expressions of ATF-6, PERK, IRE1 and GRP78 after RUT treatment. It was observed that the expressions of NF-kB, TNF-a, IL-6, JAK2 and STAT3 in the inflammatory pathway increased after VLP administration, while RUT treatment decreased the levels of these markers. It is also among the data obtained that the levels of markers that play a role in the regulation of apoptosis (Bax, Bcl-2, kaspaz-3, pERK, pJNK) or autophagy (Beclin-1, LC3A, LC3B) approach the control group after RUT treatment.Conclusions: Taken together, it was determined that RUT treatment protected against liver and kidney damage by attenuating VLP-induced oxidative stress, ER stress, inflammation, apoptosis and autophagy.