The role of GRP78/ATF6/IRE1 and caspase-3/Bax/Bcl2 signaling pathways in the protective effects of gallic acid against cadmium-induced liver damage in rats | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 10، دوره 26، شماره 11، بهمن 2023، صفحه 1326-1333 اصل مقاله (484.14 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2023.71343.15525 | ||
| نویسندگان | ||
| volkan Gelen* 1؛ Emin Sengul2، 3؛ Serkan Yildirim4؛ İrfan Cinar5 | ||
| 1Department of Physiology, Faculty of Veterinary Medicine, Kafkas University, Kars, Turkey | ||
| 2Department of Physiology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey | ||
| 3Department of Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey | ||
| 4Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey | ||
| 5Department of Pharmacology, Faculty of Medicine, Kastamonu University, Kastamonu, Turkey | ||
| چکیده | ||
| Objective(s): Cadmium (CD) causes widespread and severe toxic effects on various tissues. Studies have shown that apoptosis, inflammation, and endoplasmic reticulum stress play a role in organ damage caused by CD. Phenolic compounds with strong antioxidant effects are found in various fruits and vegetables. One of these compounds is Gallic acid (GA), which is found both free and hydrolyzable in grapes, pomegranate, tea, hops, and oak bark. Result of various studies show that GA has active antioxidant, anti-inflammatory, and anti-apoptotic properties. In our study, we investigated the mechanism of the protective effect of GA on CD-induced hepatotoxicity in rats. Materials and Methods: In this study, 50 adult male Sprague Dawley rats weighing approximately 200–250 g were used and the rats were divided into 5 groups: Control, CD, GA50+CD, GA100+CD, and GA100. The rats were treated with GA (50 and 100 mg/kg body weight), and Cd (6.5 mg/kg) was administrated to the rats for 5 consecutive days. The liver enzymes, TB levels in serum samples, oxidative stress, inflammation, ER stresses, apoptosis marker, histopathology, 8-OHDG, and caspase-3 positivity were analyzed. Results: CD administration significantly increased liver enzyme levels (AST, ALT, ALP, and LDH), MDA, IL-1-β, IFN-γ, TNF-α, IL-10, IL-6, GRP78, CHOP, ATF6, p -IRE1, sXBP, Bax mRNA expression, Caspase 3, and 8-OHdG expression (P<0.05). These values were found to be significantly lower in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). CD administration significantly decreased the expression levels of TB, IL-4, SOD, GSH, CAT, GPX, and Bcl-2 mRNA (P<0.05). These values were found to be significantly higher in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). Conclusion: The results of the present study indicated that GA prevented Cd-induced hepatic oxidative stress, inflammation, ER stress, apoptosis, and tissue damage in rats. | ||
| کلیدواژهها | ||
| Apoptosis؛ Cadmium؛ Endoplasmic reticulum - stress؛ Gallic acid؛ Hepatotoxicity؛ Inflammation | ||
| مراجع | ||
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1. Sankhla MS, Kumari M, Nandan M, Kumar R, Agrawal P. Heavy metals contamination in water and their hazardous effect on human health-a review. Int J Curr Microbiol App Sci 2016;10:759-766. 2. Pandey G, Madhuri S. Heavy metals causing toxicity in animals and fishes. Res J Animal Veterinary and Fishery Sci 2014;2:17-23. 3. Zhang W, Zhi J, Cui Y, Zhang F, Habyarimana A, Cambier C, et al. Potentiated interaction between ineffective doses of budesonide and formoterol to control the inhaled cadmium-induced up-regulation of metalloproteinases and acute pulmonary inflammation in rats. PLoS One 2014;10:e109136. 4. Sarwar N, Malhi SS, Zia MH, Naeem A, Bibi S, et al. Role of mineral nutrition in minimizing cadmium accumulation by plants. J Sci Food Agric 2010;90:925-937. 5. Prankel SH, Nixon RM, Phillips CJC. Implications for the human food chain of models of cadmium accumulation in sheep. Environ Res 2005;97:348-358. 6. Alonso ML, Montaña FP, Miranda M, Castillo C, Hernandez J, Benedito JL. Cadmium and lead accumulation in cattle in NW Spain. Vet Hum Toxicol 2003;45:128-130. 7. Rahimi E. Lead and cadmium concentrations in goat, cow, sheep, and buffalo milks from different regions of Iran. Food Chem 2013;136: 389-391. 8. Horiguchi H. Anemia induced by cadmium intoxication. Nihon Eiseigaku Zasshi 2007;62: 888-904. 9. Horiguchi H, Oguma E, Kayama F. Cadmium induces anemia through interdependent progress of hemolysis, body iron accumulation, and insufficient erythropoietin production in rats. Toxicol Sci 2011;122:198-210. 10. Josthna P, Geetharathan T, Sujatha P, Deepika G. Accumulation of lead and cadmium in the organs and tissues of the albino rat. Int J Pharm Life Sci 2012;12: 2186-2189. 11. Andjelkovic M, Buha Djordjevic A, Antonijevic E, Antonijevic B, Stanic M, Kotur-Stevuljevic J. Toxic effect of acute cadmium and lead exposure in rat blood, liver, and kidney. Int J Environ Res Public Health 2019;16:1-21. 12. Ansari MA, Raish M, Ahmad A, Alkharfy KM, Ahmad SF, Attia SM, et al. Sinapic acid ameliorates cadmium-induced nephrotoxicity: In vivo possible involvement of oxidative stress, apoptosis, and inflammation via NF-κB downregulation. Environ Toxicol Pharmacol 2017;51:100-107. 13. Refaie MM, El-Hussieny M, Zenhom NM. Protective role of nebivolol in cadmium-induced hepatotoxicity via downregulation of oxidative stress, apoptosis, and inflammatory pathways. Environ Toxicol Pharmacol 2018;58:212-219. 14. Prozialeck WC, Edwards JR. Mechanisms of cadmium-induced proximal tubule injury: New insights with implications for biomonitoring and therapeutic interventions. J Pharmacol Exp Ther 2012;343:2-12. 15. Noor KK, Ijaz MU, Ehsan N, Tahir A, Yeni DK, Neamul Kabir Zihad SM, et al. Hepatoprotective role of vitexin against cadmium-induced liver damage in male rats: A biochemical, inflammatory, apoptotic and histopathological investigation. Biomed Pharmacother 2022;150:112934 16. Alharbi N, Elobeid M, Virk P. Protective effect of quercetin treatment against cadmium-induced oxidative stress in a male rat model. Pakistan J Zool 2019;51:2287-2296. 17. Oboh G, Adebayo AA, Ademosun AO, Olowokere OG. Rutin alleviates cadmium-induced neurotoxicity in Wistar rats: Involvement of modulation of nucleotide-degrading enzymes and monoamine oxidase. Metab Brain Dis 2019;34:1181-1190. 18. Abu-El-Zahab HSH, Hamza RZ, Montaser MM, El-Mahdi MM, Al-Harthi WA. Anti-oxidant, anti-apoptotic, antigenotoxic, and hepatic ameliorative effects of L-carnitine and selenium on cadmium-induced hepatotoxicity and alterations in liver cell structure in male mice. Ecotoxicol Environ Saf 2019;173:419-428. 19. Ramkumar KM, Vijayakumar RS, Vanitha P, Suganya N, Manjula C, Rajaguru P, et al. Protective effect of gallic acid on alloxan-induced oxidative stress and osmotic fragility in rats. Hum Exp Toxicol 2014;33:638-649. 20. Bai J, Zhang Y, Tang C, Hou Y, Ai X, Chen X, et al. Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. Biomed Pharmacother 2021;133:110985. 21. Zhang P, Ye J, Dai J, Wang Y, Chen G, Hu J, Hu Q, Fei J. Gallic acid inhibits osteoclastogenesis and prevents ovariectomy-induced bone loss. Front Endocrinol (Lausanne) 2022;13:963237. 22. Inoue M, Sakaguchi N, Isuzugawa K, Tani H, Ogihara Y. Role of reactive oxygen species in gallic acid-induced apoptosis. Biol Pharm Bull 2000;23:1153–1157. 23. Dkhil MA, Al-Quraishy S, Diab MM, Othman MS, Aref AM, Abdel Moneim AE. The potential protective role of Physalis peruviana L. fruit in cadmium-induced hepatotoxicity and nephrotoxicity. Food Chem Toxicol 2014;74:98-106. 24. Vijaya Padma V, Sowmya P, Arun Felix T, Baskaran R, Poornima P. Protective effect of gallic acid against lindane induced toxicity in experimental rats. Food Chem Toxicol 2011;49:991-998. 25. Yazıhan N, Koçak MK, Akçıl E, Erdem O, Sayal A, Güven C, Akyürek N. Involvement of galectin-3 in cadmium-induced cardiac toxicity. Anadolu Kardiyol Derg 2011;11:479-484. 26. Akbari G, Savari F, Mard SA, Rezaie A, Moradi M. Gallic acid protects the liver in rats against injuries induced by transient ischemia-reperfusion through regulating microRNAs expressions. Iran J Basic Med Sci 2019;22:439-444. 27. Nouri A, Salehi-Vanani N, Heidarian E. Anti-oxidant, anti-inflammatory and protective potential of gallic acid against paraquat-induced liver toxicity in male rats. Avicenna J Phytomed 2021;11:633-644. 28. Sengul E, Gelen V, Yildirim S, Tekin S, Dag Y. The effects of selenium in acrylamide-ınduced nephrotoxicity in rats: Roles of oxidative stress, ınflammation, apoptosis, and DNA damage. Biol Trace Elem Res 2021;199:173-184. 29. Abarikwu SO, Njoku RC, Lawrence CJ, Charles IA, Ikewuchi JC. Rutin ameliorates oxidative stress and preserves hepatic and renal functions following exposure to cadmium and ethanol. Pharm Biol 2017;55:2161-2169. 30. Hogervorst J, Plusquin M, Vangronsveld J, Nawrot T, Cuypers A, Van Hecke E, Roels HA, Carleer R, Staessen JA. House dust as possible route of environmental exposure to cadmium and lead in the adult general population. Environ Res 2007;103:30-37. 31. Nordberg M, Nordberg GF. Metallothionein and cadmium toxicology-historical review and commentary. Biomolecules 2022;12:1-15. 32. De S, Sen T, Chatterjee M. Reduction of oxidative stress by an ethanolic extract of leaves of Piper betle (Paan) Linn. decreased methotrexate-induced toxicity. Mol Cell Biochem 2015;409:191-197. 33. Bouhlali EDT, Derouich M, Hmidani A, Bourkhis B, Khouya T, Filali-Zegzouti Y, et al. Protective effect of Phoenix dactylifera L. seeds against paracetamol-induced hepatotoxicity in rats: A comparison with vitamin C. Sci World J 2021;2021:6618273. 34. Leutner S, Eckert A, Müller WE. ROS generation, lipid peroxidation, and anti-oxidant enzyme activities in the aging brain. J Neural Transm (Vienna). 2001;108:955-967. 35. Kaur G, Shivanandappa TB, Kumar M, Kushwah AS. Fumaric acid protects the cadmium-induced hepatotoxicity in rats: Owing to its anti-oxidant, anti-inflammatory action and aid in recast the liver function. Naunyn Schmiedebergs Arch Pharmacol 2020;393:1911-1920. 36. Gelen V, Şengül E, Yıldırım S, Senturk E, Tekin S, Kükürt A. The protective effects of hesperidin and curcumin on 5-fluorouracil-induced nephrotoxicity in mice. Environ Sci Pollut Res Int 2021;28:47046-47055. 37. Ma Y, Su Q, Yue C, Zou H, Zhu J, Zhao H, et al. The effect of oxidative stress-ınduced autophagy by cadmium exposure in kidney, liver, and bone damage, and neurotoxicity. Int J Mol Sci 2022;23:1-17. 38. Kahkeshani N, Saeidnia S, Abdollahi M. Role of anti-oxidants and phytochemicals on acrylamide mitigation from food and reducing its toxicity. J Food Sci Technol 2015;52:3169-3186. 39. Kunle-Alabi OT, Akindele OO, Odoh MI, Oghenetega BO, Raji Y. Comparative effects of coconut water and N-Acetyl cysteine on the hypothalamic-pituitary-gonadal axis of male rats. Songklanakarin J Sci Technol 2017;39:759-764. 40. Gong ZG, Wang XY, Wang JH, Fan RF, Wang L. Trehalose prevents cadmium-induced hepatotoxicity by blocking the Nrf2 pathway, restoring autophagy, and inhibiting apoptosis. J Inorg Biochem 2019;192:62-71. 41. Fang J, Yin H, Yang Z, Tan M, Wang F, Chen K, et al. Vitamin E protects against cadmium-induced sub-chronic liver injury associated with the inhibition of oxidative stress and activation of the Nrf2 pathway. Ecotoxicol Environ Saf 2021;208:111610. 42. Ojeaburu SI, Oriakhi K. Hepatoprotective, anti-oxidant and, anti-inflammatory potentials of gallic acid in carbon tetrachloride-induced hepatic damage in Wistar rats. Toxicol Rep 2021;8:177-185. 43. Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, et al. The role of oxidative stress and anti-oxidants in liver diseases. Int J Mol Sci 2015;16:26087-26124. 44. Kumar A, Siddiqi NJ, Alrashood ST, Khan HA, Dubey A, Sharma B. Protective effect of eugenol on hepatic inflammation and oxidative stress induced by cadmium in male rats. Biomed Pharmacother 2021;139:111588. 45. 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. 46. Shah A, Vaidya NK, Bhat HK, Kumar A. HIV-1 gp120 induces type-1 programmed cell death through ER stress employing IRE1α, JNK, and AP-1 pathway. Sci Rep 2016;6:1-13. 47. Flessa CM, Kyrou I, Nasiri-Ansari N, Kaltsas G, Kassi E, Randeva HS. Endoplasmic reticulum stress in nonalcoholic (metabolic associated) fatty liver disease (NAFLD/MAFLD). J Cell Biochem 2022;123:1585-1606. 48. Guo Y, Guo R, Su Y, Fu J, Wang S, Kong Y, et al. The PERK/eIF2α/ATF4/CHOP pathway plays a role in regulating monocrotaline-induced endoplasmic reticulum stress in rat liver. Res Vet Sci 2020;130:237-239. 49. Zhang C, Ge J, Lv M, Zhang Q, Talukder M, Li JL. Selenium prevents cadmium-induced hepatotoxicity through modulation of endoplasmic reticulum-resident selenoproteins and attenuation of endoplasmic reticulum stress. Environ Pollut 2020;260:113873. 50. Obafemi TO, Jaiyesimi KF, Olomola AA, Olasehinde OR, Olaoye OA, Adewumi FD, et al. The combined effect of metformin and gallic acid on inflammation, anti-oxidant status, endoplasmic reticulum (ER) stress, and glucose metabolism in fructose-fed streptozotocin-induced diabetic rats. Toxicol Rep 2021;8:1419-1427. 51. Karamese M, Guvendi B, Karamese SA, Cinar I, Can S, Erol HS, et al. The protective effects of epigallocatechin gallate on lipopolysaccharide-induced hepatotoxicity: An in vitro study on Hep3B cells. Iran J Basic Med Sci 2016;19:483-489. 52. Zhang H, Yan J, Xie Y, Chang X, Li J, Ren C, et al. Dual role of cadmium in rat liver: Inducing liver injury and inhibiting the progression of early liver cancer. Toxicol Lett 2022;355:62-81. 53. Qu D, Jiang M, Huang D, Zhang H, Feng L, Chen Y, et al. Synergistic effects of the enhancements to mitochondrial ROS, p53 activation and apoptosis generated by aspartame and potassium sorbate in HepG2 cells. Molecules 2019;24:1-12. 54. Chen Y, Zhang W, Guo X, Ren J, Gao A. The crosstalk between autophagy and apoptosis was mediated by the phosphorylation of Bcl-2 and beclin1 in benzene-induced hematotoxicity. Cell Death Dis 2019;10:1-15. 55. Sengul E, Gelen V, Yildirim S, Cinar İ, Aksu EH. Effects of naringin on oxidative stress, inflammation, some reproductive parameters, and apoptosis in acrylamide-induced testis toxicity in rat. Environ Toxicol 2023;38:798-808. 56. Tanaka M, Sato A, Kishimoto Y, Mabashi-Asazuma H, Kondo K, Iida K. Gallic acid ınhibits lipid accumulation via AMPK pathway and suppresses apoptosis and macrophage-mediated ınflammation in hepatocytes. Nutrients 2020;20:1-14. 57. Kandemir FM, Yıldırım S, Kucukler S, Caglayan C, Darendelioğlu E, Dortbudak MB. Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach. Food Chem Toxicol 2020;138:111190. 58. Stepniak J, Karbownik-Lewinska M. 17β-estradiol prevents experimentally-induced oxidative damage to membrane lipids and nuclear DNA in porcine ovary. Syst Biol Reprod Med 2016;62:17-21. 59. Cadet J. Oxidative degradation pathways of cellular DNA: Product formation and mechanistic insights. Free Radic Biol Med 2014;75:S2. 60. Gelen V, Şengül E, Yıldırım S, Atila G. The protective effects of naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats. Iran J Basic Med Sci 2018;21:404–410. | ||
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