Abstract
This study investigated the ameliorative effect of protocatechuic acid (PCA) in oxidative stress induced by cisplatin (CPL) in the brain and liver of Wistar rats and its involvement in the activation of nuclear factor-kappaB (NF-κB) and p53 gene pathways in cisplatin-induced brain toxicity. Experimental animals were randomly assigned to five groups. Group A (control) received normal saline orally for five days. Group B received a single dose of CPL (7 mg/kg body weight) on the 5th day intraperitoneally. Group C was administered 10 mg/kg/day of PCA orally for 5 days and CPL (7 mg/kg body weight) on the 5th day intraperitoneally. Group D received 20 mg/kg/day of PCA orally for 5 days and CPL (7 mg/kg body weight) on the 5th day intraperitoneally. Group E received 20 mg/kg/day of PCA orally for 5 days to study the effect of PCA at a higher dose. The rats were sacrificed on the 6th day. The biochemical assessments carried out included liver function test, serum lipid profile, and hepatic and neuronal antioxidant status. Histoarchitecture of the liver and brain and neuronal expressions of NF-κB and p53 were assessed through staining techniques. PCA maintained the serum protein, albumin, lipid profile, and prevented lipid peroxidation and reduction in the activities of antioxidant enzymes induced by a single dose of CPL. Moreover, PCA alleviated the CPL-induced degeneration of the hepatocytes, neuronal injuries and reduced the expressions of the neuronal NF-κB and p53 gene. Our data showed that PCA might be exerting its antioxidant activities in the brain through NF-kB and p53-dependent pathways. Overall, our results indicated that PCA could attenuate oxidative stress induced by CPL in both organs and also modulate the expression of NF-kB and p53 in the brain.
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References
Adefegha SA, Oboh G, Omojokun OS (2015) Modulatory effect of protocatechuic acid on cadmium induced nephrotoxicity and hepatoxicity in rats in vivo. Springerplus 4:619
Aldossary SA (2019) Review on pharmacology of cisplatin: clinical use, toxicity and mechanism of resistance of cisplatin. Biomed Pharmacol J 12(1):7–15
Arain SQ, Talpur FN, Channa NA, Ali MS, Afridi HI (2017) Serum lipid profile as a marker of liver impairment in hepatitis B Cirrhosis patients. Lipids Health Dis 16:51
Aubrey B, Kelly G, Janic A, Herold MJ, Strasser A (2018) How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ 25:104–113
Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888
Catalá A, Díaz M (2016) Editorial: impact of lipid peroxidation on the physiology and pathophysiology of cell membranes. Front Physiol 7:423
Ciftci O, Disli OM, Timurkaan N (2013) Protective effects of protocatechuic acid on TCDD-induced oxidative and histopathological damage in the heart tissue of rats. Toxicol Industl Health 29(9):806–811
Cui Y (2017) RIG-I: a double-edged sword between inflammation and cancer. Integr Cancer Sci Therap 4(2):1–3
Farombi EO, Adedara IA, Awoyemi OV, Njoku CR, Micah GO, Esogwa CU, Owumi SE, Olopade JO (2016) Dietary protocatechuic acid ameliorates dextran sulphate sodium induced ulcerative colitis and hepatotoxicity in rats. Food Funct 7(2):913–921
Gao L, Wu W-F, Dong L, Ren G-L, Li H-D, Yang Q, Li X-F, Xu T, Li Z, Wu B-M, Ma T-T, Huang C, Huang Y, Zhang L, Lv X, Li J, Meng X-M (2016) Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing nox-mediated oxidative stress and renal inflammation. Front Pharmacol 7:479
Guttenplan JB, Chen KM, Sun YW, Kosinska W, Zhou Y, Kim SA, Sung Y, Gowda K, Amin S, Stoner GD, El-Bayoumy K (2016) Effects of black raspberry extract and protocatechuic acid on carcinogen-dna adducts and mutagenesis, and oxidative stress in rat and human oral cells. Cancer Prev Res 9:704–712
Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249(22):7130–7139
Islam SS, Al-Sharif I, Sultan A, Al-Mazrou A, Remmal A, Aboussekhra A (2018) Eugenol potentiates cisplatin anti-cancer activity through inhibition of ALDH-positive breast cancer stem cells and the NF-kappaB signaling pathway. Mol Carcinog 57(3):333–346
Kakkar S, Bais S (2014) A review on protocatechuic acid and its pharmacological potential. ISRN Pharmacol, Article ID 952943
Kim HJ, Park DJ, Kim JH et al (2015) Glutamine protects against cisplatin induced nephrotoxicity by decreasing cisplatin accumulation. J Pharmacol Sci 127(1):117–126
Krzysztoforska K, Mirowska-Guzel D, Widy-Tyszkiewicz E (2017) Pharmacological effects of protocatechuic acid and its therapeutic potential in neurodegenerative diseases: review on the basis of in vitro and in vivo studies in rodents and humans. Nutr Neurosci 26:1–11
Lingappan K (2018) NF-κB in oxidative stress. Curr Opin Toxicol 7:81–86
Liu CL, Lim YP, Hu ML (2013) Fucoxanthin enhances cisplatin-induced cytotoxicity via NFkappa B-mediated pathway and downregulates DNA repair gene expression in human hepatoma HepG2 cells. Mar Drugs 11(1):50–66
Liu Y, Sun X, Zhang Y, Wu H, Wang H, Yang R (2019) Protocatechuic acid inhibits TGF-β1-induced proliferation and migration of human airway smooth muscle cells. J Pharmacol Sci 139:9–14
Makovec T (2019) Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol Oncol 53(2):148–158
Mantovani F, Collavin L, Del Sal G (2019) Mutant p53 as a guardian of the cancer cell. Cell Death Differ 26:199–212
Mendrysa S, Ghassemifar S, Malek R (2011) p53 in the CNS: perspectives on development, stem cells, and cancer. Gene Cancer 2(4):431–442
Misra HP, Fridovich I (1972) The univalent reduction of oxygen by reduced flavins and quinines. J BIol Chem 247:188–192
Molehin OR, Adeyanju AA, Adefegha SA, Akomolafe SF (2018) Protocatechuic acid mitigates adriamycin-induced reproductive toxicities and hepatocellular damage in rats. Comp Clin Path 27(6):1681–1689
Nimse SB, Pal D (2015) Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv 5:27986–28006
NRC (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, National Academies Press, Washington, DC
O’Grady S, Finn SP, Cuffe S, Richard DJ, O’Byrne KJ, Barr MP (2014) The role of DNA repair pathways in cisplatin resistant lung cancer. Cancer Treat Rev 40:1161–1170
Oso BJ, Olaoye IF (2020) Comparative in vitro studies of antiglycemic potentials and molecular docking of Ageratum conyzoides L. and Phyllanthus amarus L. methanolic extracts. SN App Sci 2:629
Park MH, Hong JT (2016) Roles of NF-kappaB in cancer and inflammatory diseases and their therapeutic approaches. Cells 5(2):15
Rasheduzzaman M, Jeong J, Park S (2018) Resveratrol sensitizes lung cancer cell to TRAIL by p53 independent and suppression of Akt/NF-κB signaling. Life Sci 208:208–220
Rodrigues MA, Rodrigues JL, Martins NM, Barbosa F, Curti C, Santos NA, Santos AC (2010) Carvedilol protects against the renal mitochondrial toxicity induced by cisplatin in rats. Mitochondrion 10(1):46–53
Semaming Y, Kumfu S, Pannangpetch P, Chattipakorn SC, Chattipakorn N (2014) Protocatechuic acid exerts a cardiopro-tective effect in type 1 diabetic rats. J Endocrinol 223(1):13–23
Semaming Y, Pannengpetch P, Chattipakorn SC, Chattipakorn N (2015) Pharmacological properties of protocatechuic acid and its potential roles as complementary medicine. Evid Based Complement Alternat Med 2015:593902
Singh L, Aldosary S, Saeedan AS, Ansari MN, Kaithwas G (2018) Prolyl hydroxylase 2: a promising target to inhibit hypoxia-induced cellular metabolism in cancer cells. Drug Discov Today 23(11):1873–1882
Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394
Song J, He Y, Luo C, Feng B, Ran F, Xu H, Ci Z, Xu R, Han L, Zhang D (2020) New progress in the pharmacology of protocatechuic acid: A compound ingested in daily foods and herbs frequently and heavily. Pharmacol Res 161:105109
Varshney R, Kale RK (1990) Effect of calmodulin antagonist on radiation induced lipid peroxidation in microsomes. Int J Rad Biol 58:733–743
Wang J, Tian L, Khan MN, Zhang L, Chen Q, Zhao Y, Yan Q, Fu L, Liu J (2018) Ginsenoside Rg3 sensitizes hypoxic lung cancer cells to cisplatin via blocking of NF-kappaB mediated epithelial-mesenchymal transition and stemness. Cancer Lett 415:73–85
Wang TE, Lai YH, Yang KC, Lin SJ, Chen CL, Tsai PS (2020) Counteracting cisplatin-induced testicular damages by natural polyphenol constituent honokiol. Antioxidants 9(8):723
Yamabe N, Parka JY, Lee S, Cho E, Lee S, Kang KS, Hwang GS, Kim S, Kim HY, Shibamoto T (2015) Protective effects of protocatechuic acid against cisplatin-induced renal damage in rats. J Funct Foods 19:20–27
Yu S, Gong LS, Li NF, Pan YF, Zhang L (2018) Galangin (GG) combined with cis-platin (DDP) to suppress human lung cancer by inhibition of STAT3-regulated NF-kappaB and Bcl-2/Bax signaling pathways. Biomed Pharmacother 97:213–224
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Approval was obtained from the ethics committee of McPherson University. The procedures used in this study comply with standard guidelines set up for the Care and Use of Laboratory Animals for animal experiments. The animals used received care in compliance with standard guidelines set up for the Care and Use of Laboratory Animals (NRC 2011) for animal experiments. The study was carried out in compliance with the quoted standard guidelines under the supervision of the University Ethical Review Board.
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Anne A. Adeyanju has no conflict of interest. Babatunde J. Oso has no conflict of interest. Olorunfemi R. Molehin has no conflict of interest. Joshua O. Fadero has no conflict of interest. Busayo B. Odulote has no conflict of interest.
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Adeyanju, A.A., Oso, B.J., Molehin, O.R. et al. Treatment with protocatechuic acid attenuates cisplatin-induced toxicity in the brain and liver of male Wistar rats. ADV TRADIT MED (ADTM) 23, 121–131 (2023). https://doi.org/10.1007/s13596-021-00589-0
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DOI: https://doi.org/10.1007/s13596-021-00589-0