Fatih Mehmet Kandemir1, Mustafa Ileriturk2, Cihan Gur2. 1. Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, 25240, Erzurum, Turkey. fmehmet.kandemir@atauni.edu.tr. 2. Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, 25240, Erzurum, Turkey.
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 (VPA), 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 min after 500 mg/kg VPA was given to rats for 14 days. Then, some pathways that may be involved in the damage mechanism of VPA in liver and kidney tissues were investigated using biochemical, RT-PCR and Western blotting techniques. The results displayed that the levels of MDA induced by VPA in liver and kidney tissues decreased after RUT treatment, and the levels of SOD, CAT, GPx and GSH suppressed by VPA 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-κB, TNF-α, IL-6, JAK2 and STAT3 in the inflammatory pathway increased after VPA administration, while RUT treatment decreased the levels of these markers. It was also among the data obtained that the levels of markers that played a role in the regulation of apoptosis (Bax, Bcl-2, caspase-3, pERK, pJNK) or autophagy (Beclin-1, LC3A, LC3B) approached the control group after RUT treatment. CONCLUSIONS: Taken together, it was determined that RUT treatment protected against liver and kidney damage by attenuating VPA-induced oxidative stress, ER stress, inflammation, apoptosis and autophagy.
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 (VPA), 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 min after 500 mg/kg VPA was given to rats for 14 days. Then, some pathways that may be involved in the damage mechanism of VPA in liver and kidney tissues were investigated using biochemical, RT-PCR and Western blotting techniques. The results displayed that the levels of MDA induced by VPA in liver and kidney tissues decreased after RUT treatment, and the levels of SOD, CAT, GPx and GSH suppressed by VPA 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-κB, TNF-α, IL-6, JAK2 and STAT3 in the inflammatory pathway increased after VPA administration, while RUT treatment decreased the levels of these markers. It was also among the data obtained that the levels of markers that played a role in the regulation of apoptosis (Bax, Bcl-2, caspase-3, pERK, pJNK) or autophagy (Beclin-1, LC3A, LC3B) approached the control group after RUT treatment. CONCLUSIONS: Taken together, it was determined that RUT treatment protected against liver and kidney damage by attenuating VPA-induced oxidative stress, ER stress, inflammation, apoptosis and autophagy.
Authors: Tony K L Kiang; Xiao Wei Teng; Jayakumar Surendradoss; Stoyan Karagiozov; Frank S Abbott; Thomas K H Chang Journal: Toxicol Appl Pharmacol Date: 2011-03-22 Impact factor: 4.219