Study on the anti–inflammatory effect of 3–(4–hydroxyphenyl) propionic acid in an in vitro LPS–stimulated acute kidney inflammation model
Abstract
Acute kidney injury (AKI) is a syndrome defined by a rapid decrease in glomerular filtration that can be caused by sepsis, ischemia/reperfusion injury (IRI), or nephrotoxic drugs. Human microbiota makes significant contributions to human health by enzymatic transformation of such active substances and the release of molecules such as 3–4 hydroxyphenyl propionic acid (4–HPPA). Biological effects of 4–HPPA such as anti–inflammatory and antioxidant have been reported in many studies. The aim of the research is to reveal the anti–inflammatory activity of 4–HPPA, one of the microbiota products of flavonoids (especially naringin) found in many fruits, in an in vitro LPS (lipopolysaccharide) stimulated kidney inflammation model. HEK 293 kidney cells of human origin were used as material in the research. The trial consisted of 4 groups: control group, LPS group, 4–HPPA group and 4–HPPA+LPS group. LPS and 4–HPPA were applied to the cells at different concentrations for 24 hours. Effective concentrations of LPS and 4–HPPA were investigated by MTT viability test. Finally, IL–1β, TNF–α and NFkβ gene expression analyzes responsible for inflammatory responses were investigated by qRT–PCR method. According to the findings, after 24 hours of incubation, LPS at 2.5 ng·mL-1 and 4–HPPA at 6.25 μg·mL-1 were determined to be effective concentrations for the experiment. Again, it was observed that 4–HPPA downregulated LPS–induced IL–1β, TNF–α and NFkβ gene expressions by 7, 42 and 40%, respectively. According to the data obtained from the research, it was revealed that 4–HPPA had effective anti–inflammatory properties in the in vitro LPS–stimulated kidney inflammation model. However, it was concluded that in vivo and more advanced molecular methods are needed to fully elucidate the issue.
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Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. [Internet]. 2005; 294(7):813–818. doi: https://doi.org/bpxx33
Thakar CV, Christianson A, Freyberg R, Almenoff P, Render ML. Incidence and outcomes of acute kidney injury in intensive care units: a Veterans Administration study. Crit. Care Med. [Internet]. 2009; 37(9):2552–2558. doi: https://doi.org/bwf73r
Murugan R, Karajala–Subramanyam V, Lee M, Yende S, Kong L, Carter M, Angus DC, Kellum JA. Acute kidney injury in non–severe pneumonia is associated with an increased immune response and lower survival. Kidney Int. [Internet]. 2010; 77(6):527–535. doi: https://doi.org/fwqwp3
Langenberg C, Wan L, Egi M, Bellomo R. Renal blood flow in experimental septic acute renal failure. Kidney Int. [Internet]. 2006; 69(11):1996–2002. doi: https://doi.org/bnz7pq
Bacanlı M, Başaran AA, Başaran N. The antioxidant and antigenotoxic properties of citrus phenolics limonene and naringin. Food Chem. Toxicol. [Internet]. 2015; 81:160–170. doi: https://doi.org/f7gbqz
Amini N, Sarkaki A, Dianat M, Mard SA, Ahanqarpour A, Badavi M. Protective effects of naringin and trimetazidine on remote effect of acute renal injury on oxidative stress and myocardial injury through Nrf–2 regulation. Pharmacol. Rep. [Internet]. 2019; 71(6):1059–1066. doi: https://doi.org/mvxm
Constanza KE, White BL, Davis JP, Sanders TH, Dean LL. Value–added processing of peanut skins: antioxidant capacity, total phenolics, and procyanidin content of spray–dried extracts. J. Agric. Food Chem. [Internet]. 2012; 60(43):10776–10783. doi: https://doi.org/f4b5sh
Martinez–Micaelo N, González–Abuín N, Ardèvol A, Pinent M, Blay MT.Procyanidins and inflammation: Molecular targets and health implications. BioFactors. [Internet]. 2012; 38(4):257–265. doi: https://doi.org/gtd2zm
Sawyer GM, Stevenson DE, McGhie TK, Hurst RD. Suppression of CCL26 and CCL11 generation in human alveolar epithelial cells by apple extracts containing procyanidins. J. Funct. Foods. [Internet]. 2017; 31:141–151. doi: https://doi.org/f93hzh
Fraga CG, Oteiza PI. Dietary flavonoids: Role of (−)–epicatechin and related procyanidins in cell signaling. Free Radical Biol. Med. [Internet]. 2011; 51(4):813–823. doi: https://doi.org/ctkd72
Monagas M, Urpi–Sarda M, Sánchez–Patán F, Llorach R, Garrido I, Gómez–Cordovés C Andres–Lacueva C, Bartolomé B. Insights into the metabolism and microbial biotransformation of dietary flavan–3–ols and the bioactivity of their metabolites. Food Funct. [Internet]. 2010; 1(3):233–253. doi: https://doi.org/cw88gg
Lee J. Proanthocyanidin A2 purification and quantification of American cranberry (Vaccinium macrocarpon Ait.) products. J. Funct. Foods. [Internet]. 2013; 5(1):144–153. doi: https://doi.org/mvxn
López–Cobo A, Gómez–Caravaca AM, Pasini F, Caboni MA, Segura–Carretero A, Fernández–Gutiérrez A. HPLC–DAD–ESI–QTOF–MS and HPLC–FLD–MS as valuable tools for the determination of phenolic and other polar compounds in the edible part and by–products of avocado. LWT. [Internet]. 2016; 73:505–513. doi: https://doi.org/f8249q
Appeldoorn MM, Sanders M, Vincken JP, Cheynier V, Le Guernevé C, Hollman PCH, Gruppen H. Efficient isolation of major procyanidin A–type dimers from peanut skins and B–type dimers from grape seeds. Food Chem. [Internet]. 2009; 117(4):713–720. doi: https://doi.org/fh8czf
Zhang JY, Wang M, Tian L, Genovese G, Yan P, Wilson JG, Thadhani R, Mottl AK, Appel GB, Bick AG, Sampson MG, Alper SL, Friedman DJ, Pollak MR. UBD modifies APOL1–induced kidney disease risk. Proc. Natl. Acad. Sci. USA. [Internet]. 2018; 115(13):3446–3451. doi: https://doi.org/gdbrfg
Chen Y, Wu H, Nie YC, Li PB, Shen JG, Su WW. Mucoactive effects of naringin in lipopolysaccharide–induced acute lung injury mice and beagle dogs. Environ. Toxicol. Pharmacol. [Internet]. 2014; 38(1):279–287. doi: https://doi.org/f6gj2x
Tsan MF, Gao B. Cytokine function of heat shock proteins. Am. J. Physiol. Cell Physiol. 2004; 286(4):739–744. doi: https://doi.org/cx2h33
Zhang W, Zhou P, Jiang X, Zhe Fan, Xu X, Wang F. Negative Regulation of Tec Kinase Alleviates LPS–Induced Acute Kidney Injury in Mice via the TLR4/NF–[kappa] B Signaling Pathway. Biomed Res. Int. [Internet]. 2020; 20:3152043. doi: https://doi.org/mvxq
Fu H, Hu Z, Di X, Zhang Q, Zhou R. Tenuigenin exhibits protective effects against LPS–induced acute kidney injury via inhibiting TLR4/NF–κB signaling pathway. European J. Pharmacol. [Internet]. 2016; 791:229–234. doi: https://doi.org/f9dq9z
Darehgazani R, Peymani M, Hashemi MS, Omrani MD, Movafagh A, Ghaedi K, Nasr–Esfahani MH. PPARγ ameliorated LPS induced inflammation of HEK cell line expressing both human Toll–like receptor 4 (TLR4) and MD2. Cytotechnol. [Internet]. 2016; 68(4):1337–1348. doi: https://doi.org/f8w3kd
Chen Y, Nie YC, Luo YL, Lin F, Zheng YF, Cheng GH, Wu H, Zhang KJ, Su WW, Shen JG, Li PB. Protective effects of naringin against paraquat–induced acute lung injury and pulmonary fibrosis in mice. Food Chem. Toxicol. [Internet]. 2013; 58:133–140. doi: https://doi.org/f47xw4
Pu P, Gao DM, Mohamed S, Chen J, Zhang J, Zhou XY, Zhou NJ, Xie J, Jiang H. Naringin ameliorates metabolic syndrome by activating AMP–activated protein kinase in mice fed a high–fat diet. Arch. Biochem. Biophys. [Internet]. 2012; 518(1):61–70. doi: https://doi.org/bjcwzd
Gopinath K, Sudhandiran G. Protective effect of naringin on 3–nitropropionic acid–induced neurodegeneration through the modulation of matrix metalloproteinases and glial fibrillary acidic protein. Can. J. Physiol. Pharm. [Internet]. 2016; 94(1):65–71. doi: https://doi.org/f8jksj
Feng D, Wang Y, Liu Y, Wu L, Li X, Chen Y, Chen Y, Chen Y, Xu C, Yang K, Zhou T. DC–SIGN reacts with TLR–4 and regulates inflammatory cytokine expression via NF–κB activation in renal tubular epithelial cells during acute renal injury. Clin. Exp. Immunol. [Internet]. 2018; 191(1):107–115. doi: https://doi.org/gcrf7d
Chen C, Wei YZ, He XM, Li DD, Wang GQ, Li JJ, Zhang F. Naringenin produces neuroprotection against LPS–induced dopamine neurotoxicity via the inhibition of microglial NLRP3 inflammasome activation. Front. Immunol. [Internet]. 2019; 10:936. doi: https://doi.org/gnkq96
Baggiolini M, Dewald B, Moser B: Interleukin–8 and related chemotactic cytokines–CXC and CC chemokines. Adv. Immunol. [Internet]. 1993; 55:97–179. doi: https://doi.org/dmckxf
Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. [Internet]. 1992; 6(12):3051–3064. doi: https://doi.org/gf2cs8
Kitaoka Y, Munemasa Y, Nakazawa T, Ueno S. NMDA induced interleukin–1β expression is mediated by nuclear factor–kappa B p65 in the retina. Brain Res. [Internet]. 2007; 1142:247–255. doi: https://doi.org/dfmgqm
Okun E, Griffioen KJ, Lathia JD, Tang SC, Mattson MP, Arumugam TV. Toll–like receptors in neurodegeneration. Brain Res. Rev. [Internet]. 2009; 59(2):278–292. doi: https://doi.org/ffmm6p
Peng Y, Liu L, Wang Y, Yao J, Jin F, Tao T, Yuan H, Shi L, Lu S. Treatment with toll–like receptor 2 inhibitor ortho–vanillin alleviates lipopolysaccharide–induced acute kidney injury in mice. Exp. Ther. Med. [Internet]. 2019; 18(6):4829–4837. doi: https://doi.org/gsc7ft
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