Rutin protects rat liver and kidney from sodium valproate-induce damage by attenuating oxidative stress, ER stress, inflammation, apoptosis and autophagy.
Kidney
Liver
Oxidative stress
Rutin
Sodium valproate
Toxicity
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
received:
18
12
2021
accepted:
16
03
2022
pubmed:
31
3
2022
medline:
14
7
2022
entrez:
30
3
2022
Statut:
ppublish
Résumé
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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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.
Identifiants
pubmed: 35352204
doi: 10.1007/s11033-022-07395-0
pii: 10.1007/s11033-022-07395-0
doi:
Substances chimiques
Biomarkers
0
Rutin
5G06TVY3R7
Valproic Acid
614OI1Z5WI
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6063-6074Subventions
Organisme : Atatürk Üniversitesi
ID : 2021-9188
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Zhou L, Chen L, Zeng X, Liao J, Ouyang D (2020) Ginsenoside compound K alleviates sodium valproate-induced hepatotoxicity in rats via antioxidant effect, regulation of peroxisome pathway and iron homeostasis. Toxicol Appl Pharmacol 386:114829
pubmed: 31734319
Koroglu OF, Gunata M, Vardi N, Yildiz A, Ates B, Colak C et al (2021) Protective effects of naringin on valproic acid-induced hepatotoxicity in rats. Tissue Cell 72:101526
pubmed: 33756270
Adewole KE, Attah AF, Osawe SO (2021) Exploring phytotherapeutic approach in the management of valproic acid-induced toxicity. Adv Tradit Med. https://doi.org/10.1007/s13596-021-00575-6
doi: 10.1007/s13596-021-00575-6
Chaudhary S, Ganjoo P, Raiusddin S, Parvez S (2015) Nephroprotective activities of quercetin with potential relevance to oxidative stress induced by valproic acid. Protoplasma 252:209–217
pubmed: 25000991
Oztopuz O, Turkon H, Buyuk B, Coskun O, Sehitoglu MH, Ovali MA et al (2020) Melatonin ameliorates sodium valproate-induced hepatotoxicity in rats. Mol Biol Rep 47:317–325
pubmed: 31624995
Galaly SR, Abdella EM, Mohammed HM (2014) Effects of royal jelly on genotoxicity and nephrotoxicity induced by valproic acid in albino mice. Beni-Suef Univ J Basic Appl Sci 3:1–15
Tong V, Teng XW, Chang TK, Abbott FS (2005) Valproic acid I: time course of lipid peroxidation biomarkers, liver toxicity, and valproic acid metabolite levels in rats. Toxicol Sci 86:427–435
pubmed: 15858223
Kiang TK, Teng XW, Surendradoss J, Karagiozov S, Abbott FS, Chang TK (2011) Glutathione depletion by valproic acid in sandwich-cultured rat hepatocytes: role of biotransformation and temporal relationship with onset of toxicity. Toxicol Appl Pharmacol 252:318–324
pubmed: 21397622
Jin J, Xiong T, Hou X, Sun X, Liao J, Huang Z et al (2014) Role of Nrf2 activation and NF-κB inhibition in valproic acid induced hepatotoxicity and in diammonium glycyrrhizinate induced protection in mice. Food Chem Toxicol 73:95–104
pubmed: 25152329
Jahan S, Munawar A, Razak S, Anam S, Ain QU, Ullah H et al (2018) Ameliorative effects of rutin against cisplatin-induced reproductive toxicity in male rats. BMC Urol 18:1–11
Kandemir FM, Kucukler S, Caglayan C, Gur C, Batil AA, Gülçin İ (2017) Therapeutic effects of silymarin and naringin on methotrexate-induced nephrotoxicity in rats: biochemical evaluation of anti-inflammatory, antiapoptotic, and antiautophagic properties. J Food Biochem 41:e12398
Yardim A, Kandemir FM, Ozdemir S, Kucukler S, Comakli S, Gur C et al (2020) Quercetin provides protection against the peripheral nerve damage caused by vincristine in rats by suppressing caspase 3, NF-κB, ATF-6 pathways and activating Nrf2, Akt pathways. Neurotoxicology 81:137–146
pubmed: 33038355
Kucukler S, Benzer F, Yildirim S, Gur C, Kandemir FM, Bengu AS et al (2021) Protective effects of chrysin against oxidative stress and inflammation induced by lead acetate in rat kidneys: a biochemical and histopathological approach. Biol Trace Elem Res 199:1501–1514
Kandemir FM, Caglayan C, Aksu EH, Yildirim S, Kucukler S, Gur C et al (2020) Protective effect of rutin on mercuric chloride-induced reproductive damage in male rats. Andrologia 52:e13524
pubmed: 32022330
Caglayan C, Kandemir FM, Darendelioğlu E, Yıldırım S, Kucukler S, Dortbudak MB (2019) Rutin ameliorates mercuric chloride-induced hepatotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. J Trace Elem Med Biol 56:60–68
pubmed: 31442956
Çelik H, Kandemir FM, Caglayan C, Özdemir S, Çomaklı S, Kucukler S et al (2020) Neuroprotective effect of rutin against colistin-induced oxidative stress, inflammation and apoptosis in rat brain associated with the CREB/BDNF expressions. Mol Biol Rep 47:2023–2034
pubmed: 32030599
Aktaş MS, Kandemir FM, Özkaraca M, Hanedan B, Kırbaş A (2017) Protective effects of rutin on acute lung injury induced by oleic acid in rats. Kafkas Univ Vet Fak Derg 23:443–451
Semwal R, Joshi SK, Semwal RB, Semwal DK (2021) Health benefits and limitations of rutin—a natural flavonoid with high nutraceutical value. Phytochem Lett 46:119–128
Garber JC, Wayne Barbee R, Bielitzki JT, Clayton LA, Donovan JC, Hendriksen C et al (2011) Committee for the update of the guide for the care and use of laboratory animals. Guide for the care and use of laboratory animals, 8th edn. National Academy of Sciences, Washington DC
Caglayan C, Kandemir FM, Yildirim S, Kucukler S, Eser G (2019) Rutin protects mercuric chloride-induced nephrotoxicity via targeting of aquaporin 1 level, oxidative stress, apoptosis and inflammation in rats. J Trace Elem Med Biol 54:69–78
pubmed: 31109623
Gad AM (2018) Study on the influence of caffeic acid against sodium valproate–induced nephrotoxicity in rats. J Biochem Mol Toxicol 32:e22175
pubmed: 29968957
Placer ZA, Cushman LL, Johnson BC (1966) Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem 16:359–364
pubmed: 6007581
Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500
pubmed: 3349599
Aebi H (1984) [13] Catalase in vitro. Methods Enzymol 105:121–126
pubmed: 6727660
Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952–958
pubmed: 971321
Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205
pubmed: 4973948
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
pubmed: 14907713
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25:402–8
pubmed: 11846609
Kandemir FM, Yıldırım S, Kucukler S, Caglayan C, Darendelioğlu E, Dortbudak MB (2020) Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: a multi-biomarker approach. Food Cheml Toxicol 138:111190
Küçükler S, Çomaklı S, Özdemir S, Çağlayan C, Kandemir FM (2021) Hesperidin protects against the chlorpyrifos-induced chronic hepato-renal toxicity in rats associated with oxidative stress, inflammation, apoptosis, autophagy, and up-regulation of PARP-1/VEGF. Environ Toxicol. https://doi.org/10.1002/tox.23156
doi: 10.1002/tox.23156
pubmed: 33908150
Ardianto C, Wardani HA, Nurrahmi N, Rahmadi M, Khotib J (2020) Alpha-lipoic acid ameliorates sodium valproate-induced liver injury in mice. Vet World 13:963
pubmed: 32636594
pmcid: 7311888
Caglayan C, Kandemir FM, Darendelioğlu E, Küçükler S, Ayna A (2021) Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms. Life Sci 281:119730
pubmed: 34147482
Kandemir FM, Caglayan C, Darendelioğlu E, Küçükler S, İzol E, Kandemir Ö (2021) Modulatory effects of carvacrol against cadmium-induced hepatotoxicity and nephrotoxicity by molecular targeting regulation. Life Sci 277:119610
pubmed: 33989663
Rakshit S, Shukla P, Verma A, Kumar Nirala S, Bhadauria M (2021) Protective role of rutin against combined exposure to lipopolysaccharide and D-galactosamine-induced dysfunctions in liver, kidney, and brain: hematological, biochemical, and histological evidences. J Food Biochem 45:e13605
pubmed: 33433008
Cihan GÜ, Kandemir F, Aydın GE (2020) Bortezomib ile Kalp Hasarı Oluşturulan Ratlarda Berberinin Oksidatif ve Nitrozatif Stres Üzerine Etkisi. Türk Doğa ve Fen Dergisi 9:118–26
Gur C, Kandemir O, Kandemir FM (2022) Investigation of the effects of hesperidin administration on abamectin-induced testicular toxicity in rats through oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, autophagy, and JAK2/STAT3 pathways. Environ Toxicol 37:401-412
Abdel-Daim MM, Abd Eldaim MA, Hassan AG (2015) Trigonella foenum-graecum ameliorates acrylamide-induced toxicity in rats: roles of oxidative stress, proinflammatory cytokines, and DNA damage. Biochem Cell Biol 93:192–198
pubmed: 25607344
Semis HS, Gur C, Ileriturk M, Kandemir FM, Kaynar O (2021) Evaluation of therapeutic effects of quercetin against achilles tendinopathy in rats via oxidative stress, inflammation, apoptosis, autophagy, and metalloproteinases. Am J Sports Med. https://doi.org/10.1177/03635465211059821
doi: 10.1177/03635465211059821
pubmed: 34908488
El-Shenawy NS (2010) Effects of insecticides fenitrothion, endosulfan and abamectin on antioxidant parameters of isolated rat hepatocytes. Toxicol In Vitro 24:1148–1157
pubmed: 20214973
Yardim A, Gur C, Comakli S, Ozdemir S, Kucukler S, Celik H et al (2022) Investigation of the effects of berberine on bortezomib-induced sciatic nerve and spinal cord damage in rats through pathways involved in oxidative stress and neuro-inflammation. NeuroToxicology. https://doi.org/10.1016/j.neuro.2022.01.011
doi: 10.1016/j.neuro.2022.01.011
pubmed: 35121005
Meligi N, Hassan H (2017) Protective effects of Eruca sativa (rocket) on abamectin insecticide toxicity in male albino rats. Environ Sci Pollut Res 24(10):9702–9712
Arora D, Siddiqui MH, Sharma PK, Singh SP, Tripathi A, Mandal P et al (2016) Evaluation and physiological correlation of plasma proteomic fingerprints for deltamethrin-induced hepatotoxicity in Wistar rats. Life Sci 160:72–83
pubmed: 27142831
Kucukler S, Caglayan C, Darendelioğlu E, Kandemir FM (2020) Morin attenuates acrylamide-induced testicular toxicity in rats by regulating the NF-κB, Bax/Bcl-2 and PI3K/Akt/mTOR signaling pathways. Life Sci 261:118301
pubmed: 32827546
Emekli-Alturfan E, Alev B, Tunali S, Oktay S, Tunali-Akbay T, Ozturk LK et al (2015) Effects of edaravone on cardiac damage in valproic acid induced toxicity. Ann Clin Lab Sci 45:166–172
pubmed: 25887870
Semis HS, Gur C, Ileriturk M, Kaynar O, Kandemir FM (2021) Investigation of the anti-inflammatory effects of caffeic acid phenethyl ester in a model of λ-Carrageenan–induced paw edema in rats. Hum Exp Toxicol. https://doi.org/10.1177/09603271211054436
doi: 10.1177/09603271211054436
pubmed: 34789018
Jin H, Peng X, He Y, Ruganzu JB, Yang W (2020) Tanshinone IIA suppresses lipopolysaccharide-induced neuroinflammatory responses through NF-κB/MAPKs signaling pathways in human U87 astrocytoma cells. Brain Res Bull 164:136–145
pubmed: 32860868
Semis HS, Kandemir FM, Kaynar O, Dogan T, Arikan SM (2021) The protective effects of hesperidin against paclitaxel-induced peripheral neuropathy in rats. Life Sci 287:120104
pubmed: 34743946
Zhou G-Y, Yi Y-X, Jin L-X, Lin W, Fang P-P, Lin X-Z et al (2016) The protective effect of juglanin on fructose-induced hepatitis by inhibiting inflammation and apoptosis through TLR4 and JAK2/STAT3 signaling pathways in fructose-fed rats. Biomed Pharmacother 81:318–328
pubmed: 27261609
Li Q, Yang H, Wang W, Li N, Zou X, Li Y et al (2020) Brassica rapa polysaccharides ameliorate CCl
pubmed: 31730730
Yang Y, Lin X, Huang H, Feng D, Ba Y, Cheng X et al (2015) Sodium fluoride induces apoptosis through reactive oxygen species-mediated endoplasmic reticulum stress pathway in Sertoli cells. J Environ Sci 30:81–89
Zhang S, Jiang C, Liu H, Guan Z, Zeng Q, Zhang C et al (2013) Fluoride-elicited developmental testicular toxicity in rats: roles of endoplasmic reticulum stress and inflammatory response. Toxicol Appl Pharmacol 271:206–215
pubmed: 23707774
Niu Q, Chen J, Xia T, Li P, Zhou G, Xu C et al (2018) Excessive ER stress and the resulting autophagic flux dysfunction contribute to fluoride-induced neurotoxicity. Environ Pollut 233:889–899
pubmed: 29100748
Deng H, Kuang P, Cui H, Chen L, Luo Q, Fang J et al (2016) Sodium fluoride (NaF) induces the splenic apoptosis via endoplasmic reticulum (ER) stress pathway in vivo and in vitro. Aging (Albany NY) 8:3552
Mostafa DG, Khaleel EF, Badi RM, Abdel-Aleem GA, Abdeen HM (2019) Rutin hydrate inhibits apoptosis in the brains of cadmium chloride-treated rats via preserving the mitochondrial integrity and inhibiting endoplasmic reticulum stress. Neurol Res 41:594–608
pubmed: 30973085
Celik H, Kucukler S, Ozdemir S, Comakli S, Gur C, Kandemir FM et al (2020) Lycopene protects against central and peripheral neuropathy by inhibiting oxaliplatin-induced ATF-6 pathway, apoptosis, inflammation and oxidative stress in brains and sciatic tissues of rats. NeuroToxicology 80:29–40
pubmed: 32544411
Tabeshpour J, Mehri S, Abnous K, Hosseinzadeh H (2020) Role of oxidative stress, MAPKinase and apoptosis pathways in the protective effects of thymoquinone against acrylamide-induced central nervous system toxicity in rat. Neurochem Res 45:254–267
pubmed: 31728856
Thangarajan S, Vedagiri A, Somasundaram S, Sakthimanogaran R, Murugesan M (2018) Neuroprotective effect of morin on lead acetate-induced apoptosis by preventing cytochrome c translocation via regulation of Bax/Bcl-2 ratio. Neurotoxicol Teratol 66:35–45
pubmed: 29353014
Dhanasekaran DN, Reddy EP (2008) JNK signaling in apoptosis. Oncogene 27:6245–6251
pubmed: 18931691
pmcid: 3063296
Cagnol S, Chambard JC (2010) ERK and cell death: mechanisms of ERK-induced cell death–apoptosis, autophagy and senescence. FEBS J 277:2–21
pubmed: 19843174
El-Dessouki AM, El Fattah MA, Awad AS, Zaki HF (2018) Zafirlukast and vincamine ameliorate tamoxifen-induced oxidative stress and inflammation: role of the JNK/ERK pathway. Life Sci 202:78–88
pubmed: 29626531
Suzuki M, Bandoski C, Bartlett JD (2015) Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling. Free Radic Biol Med 89:369–378
pubmed: 26431905
pmcid: 4684823
Wang J, Zhu H, Wang K, Yang Z, Liu Z (2020) Protective effect of quercetin on rat testes against cadmium toxicity by alleviating oxidative stress and autophagy. Environ Sci Pollut Res 27:25278–25286
Rahaman MS, Banik S, Akter M, Rahman MM, Sikder MT, Hosokawa T et al (2020) Curcumin alleviates arsenic-induced toxicity in PC12 cells via modulating autophagy/apoptosis. Ecotoxicol Environ Saf 200:110756
pubmed: 32464442