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BMC Complementary Medicine and Therapies

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Open Access 01-12-2023 | Research

Gallic acid rescues uranyl acetate induced-hepatic dysfunction in rats by its antioxidant and cytoprotective potentials

Authors: Ibtisam M. H. Elmileegy, Hanan S. A. Waly, Alshaimaa A. I. Alghriany, Nasser S. Abou Khalil, Sara M. M. Mahmoud, Eman A. Negm

Published in: BMC Complementary Medicine and Therapies | Issue 1/2023

Abstract

Background

The liver was identified as a primary target organ for the chemo-radiological effects of uranyl acetate (UA). Although the anti-oxidant and anti-apoptotic properties of gallic acid (GA) make it a promising phytochemical to resist its hazards, there is no available data in this area of research.

Methods

To address this issue, eighteen rats were randomly and equally divided into three groups. One group was received carboxymethyl cellulose (vehicle of GA) and kept as a control. The UA group was injected intraperitoneally with UA at a single dose of 5 mg/kg body weight. The third group (GA + UA group) was treated with GA orally at a dose of 100 mg/kg body weight for 14 days before UA exposure. UA was injected on the 15th day of the experiment in either the UA group or the GA + UA group. The biochemical, histological, and immunohistochemical findings in the GA + UA group were compared to both control and UA groups.

Results

The results showed that UA exposure led to a range of adverse effects. These included elevated plasma levels of aspartate aminotransferase, lactate dehydrogenase, total protein, globulin, glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very-low-density lipoprotein and decreased plasma levels of high-density lipoprotein cholesterol. The exposure also disrupted the redox balance, evident through decreased plasma total antioxidant capacity and hepatic nitric oxide, superoxide dismutase, reduced glutathione, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase and increased hepatic oxidized glutathione and malondialdehyde. Plasma levels of albumin and alanine aminotransferase did not significantly change in all groups. Histopathological analysis revealed damage to liver tissue, characterized by deteriorations in tissue structure, excessive collagen accumulation, and depletion of glycogen. Furthermore, UA exposure up-regulated the immuno-expression of cleaved caspase-3 and down-regulated the immuno-expression of nuclear factor-erythroid-2-related factor 2 in hepatic tissues, indicating an induction of apoptosis and oxidative stress response. However, the pre-treatment with GA proved to be effective in mitigating these negative effects induced by UA exposure, except for the disturbances in the lipid profile.

Conclusions

The study suggests that GA has the potential to act as a protective agent against the adverse effects of UA exposure on the liver. Its ability to restore redox balance and inhibit apoptosis makes it a promising candidate for countering the harmful effects of chemo-radiological agents such as UA.

Yue YC, Li MH, Wang HB, Zhang BL, He W. The toxicological mechanisms and detoxification of depleted uranium exposure. Environ Health Prev Med. 2018;23:1–9.CrossRef

Soltani M, Zarei MH, Salimi A, Pourahmad J. Mitochondrial protective and antioxidant agents protect toxicity induced by depleted uranium in isolated human lymphocytes. J Environ Radioact. 2019;203:112–6.PubMedCrossRef

Shaki F, Hosseini MJ, Shahraki J, Ghazi-Khansari M, Pourahmad J. Toxicity of depleted uranium on isolated liver mitochondria: a revised mechanistic vision for justification of clinical complication of depleted uranium (DU) on liver. Toxicol Environ Chem. 2013;95:1221–34.CrossRef

Yuan Y, Zheng J, Zhao T, Tang X, Hu N. Hydrogen sulfide alleviates uranium-induced acute hepatotoxicity in rats: role of antioxidant and antiapoptotic signaling. Environ Toxicol. 2017;32:581–93.PubMedCrossRef

Yuan G, Dai S, Yin Z, Lu H, Jia R, Xu J, Song X, Li L, Shu Y, Zhao X. Sub-chronic lead and cadmium co-induce apoptosis protein expression in liver and kidney of rats. Int J Clin Exp Pathol. 2014;7:2905.PubMedPubMedCentral

Šömen Joksić A, Katz SA. Chelation therapy for treatment of systemic intoxication with uranium: a review. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2015;50:1479–88.PubMedCrossRef

Ohmachi Y. Decorporation agents for internal radioactive contamination. J Pharm Soc Jpn. 2015;135:557–63.CrossRef

Waly H, Ragab SMM, Hassanein KMA, Abou Khalil NS, Ahmed EA. Uranium exposure increases spermatocytes metaphase apoptosis in rats: inhibitory effect of thymoquinone and N-acetylcysteine. Gen Physiol Biophys. 2019;38:145–55.PubMedCrossRef

Nair GG, Nair CKK. Radioprotective effects of gallic acid in mice. Biomed Res Int. 2013;2013:953079.PubMedPubMedCentralCrossRef

10.

Ferk F, Chakraborty A, Jäger W, Kundi M, Bichler J, Mišík M, Wagner KH, Grasl-Kraupp B, Sagmeister S, Haidinger G, Hoelzl C, Nersesyan A, Dušinská M, Simić T, Knasmüller S. Potent protection of gallic acid against DNA oxidation: results of human and animal experiments. Mutat Res Fundam Mol Mech Mutagen. 2011;715:61–71.CrossRef

11.

Ma S, Lv L, Lu Q, Li Y, Zhang F, Lin M, Gao D, Liu L, Tian X, Yao J. Gallic acid attenuates dimethylnitrosamine-induced acute liver injury in mice through Nrf2-mediated induction of heme oxygenase-1 and glutathione-s-transferase alpha 3. Med Chem. 2014;4:663–9.CrossRef

12.

Esmaeilzadeh M, Heidarian E, Shaghaghi M, Roshanmehr H, Najafi M, Moradi A, Nouri A. Gallic acid mitigates diclofenac-induced liver toxicity by modulating oxidative stress and suppressing IL-1β gene expression in male rats. Pharm Biol. 2020;58:590–6.PubMedPubMedCentralCrossRef

13.

Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.PubMedCrossRef

14.

Saravanan R, Pari L. Effect of a novel insulinotropic agent, succinic acid monoethyl ester, on lipids and lipoproteins levels in rats with streptozotocin-nicotinamide-induced type 2 Diabetes. J Biosci. 2006;31:581–7.PubMedCrossRef

15.

Rojas MM, Villalpando DM, Ferrer M, Alexander-Aguilera A, García HS. Conjugated linoleic acid supplemented Diet influences serum markers in Orchidectomized Sprague‐Dawley rats. Eur J Lipid Sci Technol. 2020;122:1900098.CrossRef

16.

Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351–8.PubMedCrossRef

17.

Ding AH, Nathan CF, Stuehr DJ. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for Independent production. J Immunol. 1988;141:2407–12.PubMedCrossRef

18.

Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247:3170–5.PubMedCrossRef

19.

Beutler E. Red cell metabolism. A manual of biochemical methods. 3rd ed. New York: Grune and Startton; 1984.

20.

Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem. 1969;27:502–22.PubMedCrossRef

21.

Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science. 1973;179:588–90.PubMedCrossRef

22.

Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249:7130–9.PubMedCrossRef

23.

Bancroft JD, Gamble M. Theory and practice of histological techniques. 6th ed. Churchill Livingstone: Elsevier Health Sciences; 2008.

24.

Bhutda S, Surve MV, Anil A, Kamath K, Singh N, Modi D, Banerjee A. Histochemical staining of collagen and identification of its subtypes by picrosirius red dye in mouse reproductive tissues. Bio-protocol. 2017;7:e2592.PubMedPubMedCentralCrossRef

25.

Atia MM, Alghriany AA. Adipose-derived mesenchymal stem cells rescue rat hippocampal cells from aluminum oxide nanoparticle-induced apoptosis via regulation of P53, Aβ, SOX2, OCT4, and CYP2E1. Toxicol Rep. 2021;8:1156–68.PubMedPubMedCentralCrossRef

26.

Ndrepepa G, Kastrati A. Alanine aminotransferase—a marker of cardiovascular risk at high and low activity levels. J Lab Precis Med. 2019;4:29–45.CrossRef

27.

Kimmoun A, Novy E, Auchet T, Ducrocq N, Levy B. Hemodynamic consequences of severe lactic acidosis in shock states: from bench to bedside. Crit Care. 2016;19:1–13.

28.

Nouri A, Salehi-Vanani N, Heidarian E. Antioxidant, anti-inflammatory and protective potential of gallic acid against paraquat-induced liver toxicity in male rats. Avicenna J Phytomed. 2021;11:633–44.PubMedPubMedCentral

29.

Suwalsky M, Colina J, Gallardo MJ, Jemiola-Rzeminska M, Strzalka K, Manrique-Moreno M, Sepúlveda B. Antioxidant capacity of gallic acid in vitro assayed on human erythrocytes. J Membr Biol. 2016;249:769–79.PubMedCrossRef

30.

Panghal A, Sathua KB, Flora SJS. Gallic acid and MiADMSA reversed arsenic induced oxidative/nitrosative damage in rat red blood cells. Heliyon. 2020;6:e03431.PubMedPubMedCentralCrossRef

31.

Nahar N, Mohamed S, Mustapha NM, Fong LS, Mohd Ishak NI. Gallic acid and myricetin-rich Labisia pumila extract mitigated multiple diabetic eye disorders in rats. J Food Biochem. 2021;45:e13948.PubMedCrossRef

32.

Hao Y, Ren J, Liu J, Yang Z, Liu C, Li R, Su Y. Immunological changes of chronic oral exposure to depleted uranium in mice. Toxicology. 2013;309:81–90.PubMedCrossRef

33.

Doi H, Hayashi E, Arai J, Tojo M, Morikawa K, Eguchi J, Ito T, Kanto T, Kaplan DE, Yoshida H. Enhanced B-cell differentiation driven by advanced Cirrhosis resulting in hyperglobulinemia. J Gastroenterol Hepatol. 2018;33:1667–76.CrossRef

34.

Tanaka S, Okamoto Y, Yamazaki M, Mitani N, Nakajima Y, Fukui H. Significance of hyperglobulinemia in severe chronic Liver Diseases–with special reference to the correlation between serum globulin/IgG level and ICG clearance. Hepatogastroenterology. 2007;54:2301–5.PubMed

35.

Katz A, Orellana O. Protein synthesis and the stress response. In: Biyani M, editor. Cell-free protein synthesis. Crotia: Intech; 2012. pp. 111–34.

36.

Zimmerman KL, Barber DS, Ehrich MF, Tobias L, Hancock S, Hinckley J, Binder EM, Jortner BS. Temporal clinical chemistry and microscopic renal effects following acute uranyl acetate exposure. Toxicol Pathol. 2007;35:1000–9.PubMedCrossRef

37.

Almalki DA, Alghamdi SA, Al-Attar AM. Comparative study on the influence of some medicinal plants on Diabetes induced by streptozotocin in male rats. Biomed Res Int. 2019;2019:3596287.PubMedPubMedCentralCrossRef

38.

Wang G, Wang YF, Li JL, Peng RJ, Liang XY, Chen XD, Jiang GH, Shi JF, Si-Ma YH, Xu SQ. Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an animal model. Zool Res. 2022;43:301–18.PubMedPubMedCentralCrossRef

39.

Carvalho JR, Machado MV. New insights about albumin and Liver Disease. Ann Hepatol. 2018;17:547–60.PubMedCrossRef

40.

Ali MM, Ahmed OM, Nada AS, Abdel-Reheim ES, Amin NE. Possible protective effect of naringin (a citrus bioflavonoid) against kidney injury induced by?-irradiation and/or iron overload in male rats. Int J Radiat Res. 2020;18:673–84.CrossRef

41.

Hao Y, Huang J, Gu Y, Liu C, Li H, Liu J, Ren J, Yang Z, Peng S, Wang W. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity. Toxicol Appl Pharmacol. 2015;287:306–15.PubMedCrossRef

42.

Mercantepe F, Tumkaya L, Mercantepe T, Rakici SY, Ciftel S, Ciftel S. Radioprotective effects of α2-adrenergic receptor agonist dexmedetomidine on X-ray irradiation-induced pancreatic islet cell damage. Naunyn Schmiedebergs Arch Pharmacol. 2023;396:1827–36.PubMedCrossRef

43.

Jo SK, Seol MA, Park HR, Jung U, Roh C. Ionising radiation triggers fat accumulation in white adipose tissue. Int J Radiat Biol. 2011;87:302–10.PubMedCrossRef

44.

Chen Y, Wang L, Pitzer AL, Li X, Li PL, Zhang Y. Contribution of redox-dependent activation of endothelial Nlrp3 inflammasomes to hyperglycemia-induced endothelial dysfunction. J Mol Med. 2016;94:1335–47.PubMedCrossRef

45.

Shivarudrappa AH, Ponesakki G. Lutein reverses hyperglycemia-mediated blockage of Nrf2 translocation by modulating the activation of intracellular protein kinases in retinal pigment epithelial (ARPE-19) cells. J Cell Commun Signal. 2020;14:207–21.PubMedCrossRef

46.

Parmar M, Syed S, Gray I, Ray JP. Curcumin, hesperidin, and rutin selectively interfere with apoptosis signaling and attenuate streptozotocin-induced oxidative stress-mediated hyperglycemia. Curr Neurovasc Res. 2015;12:363–74.PubMedCrossRef

47.

Variya BC, Bakrania AK, Patel SS. Antidiabetic potential of gallic acid from Emblica officinalis: improved glucose transporters and insulin sensitivity through PPAR-γ and Akt signaling. Phytomedicine. 2020;73:152906.PubMedCrossRef

48.

Abdel-Moneim A, Abd El-Twab SM, Yousef AI, Ashour MB, Reheim ESA, Hamed MAA. New insights into the in vitro, in situ and in vivo antihyperglycemic mechanisms of gallic acid and p-coumaric acid. Arch Physiol Biochem. 2022;128:1188–94.PubMedCrossRef

49.

Alkhalf MI, Khalifa FK. Blueberry extract attenuates γ-radiation-induced hepatocyte damage by modulating oxidative stress and suppressing NF-κB in male rats. Saudi J Biol Sci. 2018;25:1272–7.PubMedPubMedCentralCrossRef

50.

Lestaevel P, Bensoussan H, Racine R, Airault F, Gourmelon P, Souidi M. Transcriptomic effects of depleted uranium on acetylcholine and cholesterol metabolisms in Alzheimer’s Disease model. C R Biol. 2011;334:85–90.PubMedCrossRef

51.

Rashid S, Watanabe T, Sakaue T, Lewis GF. Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity. Clin Biochem. 2003;36:421–9.PubMedCrossRef

52.

Razzaq DF, Saleh DS, Al-Mashhadani AH. Studying the uranium pollution in reduction the levels of the C-Peptide and Vitamin D for healthy and diabetic patients in Najaf City Iraq. AIP Conf Proc. 2020;2290:030038.

53.

Hirano T. Abnormal lipoprotein metabolism in diabetic Nephropathy. Clin Exp Nephrol. 2014;18:206–9.PubMedCrossRef

54.

Zhou X, Zhang W, Liu X, Zhang W, Li Y. Interrelationship between Diabetes and periodontitis: role of hyperlipidemia. Arch Oral Biol. 2015;60:667–74.PubMedCrossRef

55.

Chen L, Chen XW, Huang X, Song BL, Wang Y, Wang Y. Regulation of glucose and lipid metabolism in health and Disease. Sci China Life Sci. 2019;62:1420–58.PubMedCrossRef

56.

Azizidoost S, Nazeri Z, Mohammadi A, Mohammadzadeh G, Cheraghzadeh M, Jafari A, Kheirollah A. Effect of hydroalcoholic ginger extract on brain HMG-CoA reductase and CYP46A1 levels in streptozotocin-induced diabetic rats. Avicenna J Med Biotechnol. 2019;11:234–8.PubMedPubMedCentral

57.

Li M, Zhou W, Dang Y, Li C, Ji G, Zhang L. Berberine compounds improves hyperglycemia via microbiome mediated colonic TGR5-GLP pathway in db/db mice. Biomed Pharmacother. 2020;132:110953.PubMedCrossRef

58.

Mansour HH, Ismael NER, Hafez HF. Modulatory effect of Moringa oleifera against gamma-radiation-induced oxidative stress in rats. Biomed Aging Pathol. 2014;4:265–72.CrossRef

59.

Paiva AA, Raposo HF, Wanschel ACBA, Nardelli TR, Oliveira HCF. Apolipoprotein CIII overexpression-induced hypertriglyceridemia increases nonalcoholic fatty Liver Disease in association with inflammation and cell death. Oxid Med Cell Longev. 2017;2017:1838679.PubMedPubMedCentralCrossRef

60.

Bai J, Lin QY, An X, Liu S, Wang Y, Xie Y, Liao J. Low-dose gallic acid administration does not improve diet-induced metabolic disorders and Atherosclerosis in apoe knockout mice. J Immunol Res. 2022;2022:7909971.PubMedPubMedCentralCrossRef

61.

Redan BW, Buhman KK, Novotny JA, Ferruzzi MG. Altered transport and metabolism of phenolic compounds in obesity and Diabetes: implications for functional food development and assessment. Adv Nutr. 2016;7:1090–104.PubMedPubMedCentralCrossRef

62.

Pourahmad J, Shaki F, Tanbakosazan F, Ghalandari R, Ettehadi HA, Dahaghin E. Protective effects of fungal β-(1→ 3)-D-glucan against oxidative stress cytotoxicity induced by depleted uranium in isolated rat hepatocytes. Hum Exp Toxicol. 2011;30:173–81.PubMedCrossRef

63.

Abou-Khalil NS, Ali MF, Ali MM, Ibrahim A. Surgical castration versus chemical castration in donkeys: response of stress, lipid profile and redox potential biomarkers. BMC Vet Res. 2020;16:1–10.CrossRef

64.

Ebaid H, Bashandy SA, Morsy FA, Al-Tamimi J, Hassan I, Alhazza IM. Protective effect of gallic acid against thioacetamide-induced metabolic dysfunction of lipids in hepatic and renal toxicity. J King Saud Univ Sci. 2023;35:102531.CrossRef

65.

de Oliveira LS, Thomé GR, Lopes TF, Reichert KP, de Oliveira JS, da Silva Pereira A, Baldissareli J, da Costa Krewer C, Morsch VM, Schetinger MRC. Effects of gallic acid on delta–aminolevulinic dehydratase activity and in the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats. Biomed Pharmacother. 2016;84:1291–9.PubMedCrossRef

66.

Guerby P, Tasta O, Swiader A, Pont F, Bujold E, Parant O, Vayssiere C, Salvayre R, Negre-Salvayre A. Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia. Redox Biol. 2021;40:101861.PubMedPubMedCentralCrossRef

67.

Laroia ST, Ganti AK, Laroia AT, Tendulkar KK. Endothelium and the lipid metabolism: the current understanding. Int J Cardiol. 2003;88:1–9.PubMedCrossRef

68.

Sun J, Morgan M, Shen RF, Steenbergen C, Murphy E. Preconditioning results in S-nitrosylation of proteins involved in regulation of mitochondrial energetics and calcium transport. Circ Res. 2007;101:1155–63.PubMedCrossRef

69.

Yan X, Zhang QY, Zhang YL, Han X, Guo SB, Li HH. Gallic acid attenuates angiotensin II-induced Hypertension and vascular dysfunction by inhibiting the degradation of endothelial nitric oxide synthase. Front Pharmacol. 2020;11:1121.PubMedPubMedCentralCrossRef

70.

Kang N, Lee JH, Lee W, Ko JY, Kim EA, Kim JS, Heu MS, Kim GH, Jeon YJ. Gallic acid isolated from Spirogyra sp. improves Cardiovascular Disease through a vasorelaxant and antihypertensive effect. Environ Toxicol Pharmacol. 2015;39:764–72.PubMedCrossRef

71.

Iizumi T, Takahashi S, Mashima K, Minami K, Izawa Y, Abe T, Hishiki T, Suematsu M, Kajimura M, Suzuki N. A possible role of microglia-derived nitric oxide by lipopolysaccharide in activation of astroglial pentose-phosphate pathway via the Keap1/Nrf2 system. J Neuroinflammation. 2016;13:1–20.CrossRef

72.

Couto GK, Britto LRG, Mill JG, Rossoni LV. Enhanced nitric oxide bioavailability in coronary arteries prevents the onset of Heart Failure in rats with Myocardial Infarction. J Mol Cell Cardiol. 2015;86:110–20.PubMedCrossRef

73.

Bahnson ESM, Koo N, Cantu-Medellin N, Tsui AY, Havelka GE, Vercammen JM, Jiang Q, Kelley EE, Kibbe MR. Nitric oxide inhibits neointimal hyperplasia following vascular injury via differential, cell-specific modulation of SOD-1 in the arterial wall. Nitric Oxide. 2015;44:8–17.PubMedCrossRef

74.

Hao Y, Huang J, Liu C, Li H, Liu J, Zeng Y, Li R. Differential protein expression in metallothionein protection from depleted uranium-induced nephrotoxicity. Sci Rep. 2016;6:38942.PubMedPubMedCentralCrossRef

75.

Shaw P, Chattopadhyay A. Nrf2–ARE signaling in cellular protection: mechanism of action and the regulatory mechanisms. J Cell Physiol. 2020;235:3119–30.PubMedCrossRef

76.

LaMonte G, Tang X, Chen JLY, Wu J, Ding CKC, Keenan MM, Sangokoya C, Kung HN, Ilkayeva O, Boros LG, Newgard GB, Chi JT. Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress. Cancer Metab. 2013;1:1–19.CrossRef

77.

Omobowale TO, Oyagbemi AA, Ajufo UE, Adejumobi OA, Ola-Davies OE, Adedapo AA, Yakubu MA. Ameliorative effect of gallic acid in doxorubicin-induced hepatotoxicity in Wistar rats through antioxidant defense system. J Diet Suppl. 2018;15:183–96.PubMedCrossRef

78.

Singhal SS, Singh SP, Singhal P, Horne D, Singhal J, Awasthi S. Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling. Toxicol Appl Pharmacol. 2015;289:361–70.PubMedPubMedCentralCrossRef

79.

Saadat M. An evidence for correlation between the glutathione S-transferase T1 (GSTT1) polymorphism and outcome of COVID-19. Clin Chim Acta. 2020;508:213–6.PubMedPubMedCentralCrossRef

80.

Song Y, Salbu B, Teien HC, Evensen Ø, Lind OC, Rosseland BO, Tollefsen KE. Hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to gamma radiation and depleted uranium singly and in combination. Sci Total Environ. 2016;562:270–9.PubMedCrossRef

81.

Zhang F, Xu Z, Gao J, Xu B, Deng Y. In vitro effect of manganese chloride exposure on energy metabolism and oxidative damage of mitochondria isolated from rat brain. Environ Toxicol Pharmacol. 2008;26:232–6.PubMedCrossRef

82.

Kowaltowski AJ, Netto LE, Vercesi AE. The thiol-specific antioxidant enzyme prevents mitochondrial permeability transition: evidence for the participation of reactive oxygen species in this mechanism. J Biol Chem. 1998;273:12766–9.PubMedCrossRef

83.

Feng RB, Wang Y, He C, Yang Y, Wan JB. Gallic acid, a natural polyphenol, protects against tert-butyl hydroperoxide-induced hepatotoxicity by activating ERK-Nrf2-Keap1-mediated antioxidative response. Food Chem Toxicol. 2018;119:479–88.PubMedCrossRef

84.

Sanjay S, Girish C, Toi PC, Bobby Z. Gallic acid attenuates isoniazid and rifampicin-induced liver injury by improving hepatic redox homeostasis through influence on Nrf2 and NF-κB signalling cascades in Wistar rats. J Pharm Pharmacol. 2021;73:473–86.PubMedCrossRef

85.

Silvestrini A, Meucci E, Ricerca BM, Mancini A. Total antioxidant capacity: biochemical aspects and clinical significance. Int J Mol Sci. 2023;24:10978.PubMedPubMedCentralCrossRef

86.

Ojeaburu SI, Oriakhi K. Hepatoprotective, antioxidant and, anti-inflammatory potentials of gallic acid in carbon tetrachloride-induced hepatic damage in Wistar rats. Toxicol Rep. 2021;8:177–85.PubMedPubMedCentralCrossRef

87.

Olayinka ET, Ore A, Ola OS, Adeyemo OA. Ameliorative effect of gallic acid on cyclophosphamide-induced oxidative injury and hepatic dysfunction in rats. Med Sci. 2015;3:78–92.

88.

Li Z, Dong X, Liu H, Chen X, Shi H, Fan Y, Hou D, Zhang X. Astaxanthin protects ARPE-19 cells from oxidative stress via upregulation of Nrf2-regulated phase II enzymes through activation of PI3K/Akt. Mol Vis. 2013;19:1656–66.PubMedPubMedCentral

89.

Moghadam D, Zarei R, Vakili S, Ghojoghi R, Zarezade V, Veisi A, Sabaghan M, Azadbakht O, Behrouj H. The effect of natural polyphenols resveratrol, gallic acid, and kuromanin chloride on human telomerase reverse transcriptase (hTERT) expression in HepG2 hepatocellular carcinoma: role of SIRT1/Nrf2 signaling pathway and oxidative stress. Mol Biol Rep. 2023;50:77–84.PubMedCrossRef

90.

Zhang L, Chen Z, Gong W, Zou Y, Xu F, Chen L, Huang H. Paeonol ameliorates diabetic renal fibrosis through promoting the activation of the Nrf2/ARE pathway via up-regulating Sirt1. Front Pharmacol. 2018;9:512.PubMedPubMedCentralCrossRef

91.

Sarhan HKA. Uranium and lead intoxication hazards induce hepatotoxicity in rats; biochemical, histochemical and histopathological studies. Egypt J Chem. 2021;64:4545–56.CrossRef

92.

Abd-Elkareem M, Abou Khalil NS, Sayed AH. Hepatotoxic responses of 4-nonylphenol on African catfish (Clarias gariepinus): antixoidant and histochemical biomarkers. Fish Physiol Biochem. 2018;44:969–81.PubMedCrossRef

93.

Guzmán L, Durán-Lara EF, Donoso W, Nachtigall FM, Santos LS. In vivo nanodetoxication for acute uranium exposure. Molecules. 2015;20:11017–33.PubMedPubMedCentralCrossRef

94.

Takada S, Watanabe T, Mizuta R. DNase γ-dependent DNA fragmentation causes karyolysis in necrotic hepatocyte. J Vet Med Sci. 2020;82:23–6.PubMedCrossRef

95.

Ramos-Tovar E, Muriel P. Molecular mechanisms that link oxidative stress, inflammation, and fibrosis in the liver. Antioxidants. 2020;9:1279.PubMedPubMedCentralCrossRef

96.

Kottmann RM, Kulkarni AA, Smolnycki KA, Lyda E, Dahanayake T, Salibi R, Honnons S, Jones C, Isern NG, Hu JZ, Nathan SD, Grant G, Phipps RP, Sime PJ. Lactic acid is elevated in Idiopathic Pulmonary Fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-β. Am J Respir Crit Care Med. 2012;186:740–51.PubMedPubMedCentralCrossRef

97.

Yellowhair M, Romanotto MR, Stearns DM, Lantz RC. Uranyl acetate induced DNA single strand breaks and AP sites in Chinese hamster ovary cells. Toxicol Appl Pharmacol. 2018;349:29–38.PubMedPubMedCentralCrossRef

98.

El-Lakkany NM, El-Maadawy WH, El-Din SHS, Saleh S, Safar MM, Ezzat SM, Mohamed SH, Botros SS, Demerdash Z, Hammam OA. Antifibrotic effects of gallic acid on hepatic stellate cells: in vitro and in vivo mechanistic study. J Tradit Complement Med. 2019;9:45–53.PubMedCrossRef

99.

Wang L, Ryu B, Kim WS, Kim GH, Jeon YJ, Wang L, Ryu B, Kim WS, Kim GH, Jeon YJ. Protective effect of gallic acid derivatives from the freshwater green alga Spirogyra sp. against ultraviolet B-induced apoptosis through reactive oxygen species clearance in human keratinocytes and zebrafish. Algae. 2017;32:379–88.CrossRef

100.

Zhou D, Yang Q, Tian T, Chang Y, Li Y, Duan LR, Li H, Wang SW. Gastroprotective effect of gallic acid against ethanol-induced gastric Ulcer in rats: involvement of the Nrf2/HO-1 signaling and anti-apoptosis role. Biomed Pharmacother. 2020;126:110075.PubMedCrossRef

Title: Gallic acid rescues uranyl acetate induced-hepatic dysfunction in rats by its antioxidant and cytoprotective potentials
Authors: Ibtisam M. H. Elmileegy
Hanan S. A. Waly
Alshaimaa A. I. Alghriany
Nasser S. Abou Khalil
Sara M. M. Mahmoud
Eman A. Negm
Publication date: 01-12-2023
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2023
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-023-04250-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Gallic acid rescues uranyl acetate induced-hepatic dysfunction in rats by its antioxidant and cytoprotective potentials

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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Isolation and structure elucidation of the compounds from Teucrium hyrcanicum L. and the investigation of cytotoxicity, antioxidant activity, and protective effect on hydrogen peroxide-induced oxidative stress