{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T12:26:49Z","timestamp":1776947209303,"version":"3.51.4"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002352","name":"Ain Shams University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002352","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Trace Elem Res"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Aloe vera<\/jats:italic> (<jats:italic>AV<\/jats:italic>) gel extracted from fresh <jats:italic>AV<\/jats:italic> leaves was chosen in this study to evaluate its antioxidant, anti-inflammatory, and antiapoptotic activities against cadmium (Cd) -induced liver injury. Forty Wistar male adult rats were equally divided into four groups. Group I (standard control) ingested with 2.5 ml\/kg b.w. of physiological saline. Group II (Cd-intoxicated) received 3 mg\/kg b.w.\/day of CdCl<jats:sub>2<\/jats:sub> dissolved in saline. Group III (<jats:italic>AV<\/jats:italic>) received 200 mg\/kg b.w.\/day of <jats:italic>AV<\/jats:italic> gel dissolved in saline. Group IV (Cd+<jats:italic>AV<\/jats:italic>) ingested with 200 mg\/kg b.w.\/day of <jats:italic>AV<\/jats:italic> gel solution along with 3 mg\/kg b.w. CdCl<jats:sub>2<\/jats:sub>. All groups were ingested orally by gavage for 3 consecutive weeks. Paraoxonase-1 (PON-1) and HSP70 were measured in serum. The deposited Cd level, nitric oxide content, lipid peroxidation, collagen-1 (COL-1), and metalloproteinase-9 (MMP-9) levels were all determined in liver tissue homogenates. Gene expression of NF-\u03baB and IL-6, Bax, and Bcl2, as well as immunohistochemistry analysis of activated caspase-3, was performed. Results showed that ingestion of <jats:italic>AV<\/jats:italic> gel greatly relieved all oxidative stress due to Cd exposure, modulated the NF-\u03baB, IL-6, Bax, and Bcl2 expression levels, and improved the apoptotic state. In conclusion, <jats:italic>AV<\/jats:italic> gel confirmed its potential ameliorating effect against liver injury induced due to Cd exposure.<\/jats:p>","DOI":"10.1007\/s12011-024-04141-4","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T02:02:41Z","timestamp":1710208961000},"page":"218-228","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Aloe vera gel relieves cadmium triggered hepatic injury via antioxidative, anti-inflammatory, and anti-apoptotic routes"],"prefix":"10.1007","volume":"203","author":[{"given":"Rasha E.","family":"Hassan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eman M.","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Germine M.","family":"Hamdy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"4141_CR1","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1007\/s12011-017-1106-z","volume":"182","author":"L Zhang","year":"2017","unstructured":"Zhang L, Huang Y, Zhu Y, Yu Z, Shao M, Luo Y (2017) Identification and characterization of cadmium-related genes in liver carcinoma. Biol Trace Elem Res 182:238\u2013247","journal-title":"Biol Trace Elem Res"},{"issue":"26","key":"4141_CR2","doi-asserted-by":"publisher","first-page":"33042","DOI":"10.1007\/s11356-020-09624-0","volume":"27","author":"TH Kim","year":"2020","unstructured":"Kim TH, Kim JH, Le Kim MD, Suh WD, Kim JE, Yeon HJ, Park YS, Kim SH, Oh YH, Jo GH (2020) Exposure assessment and safe intake guidelines for heavy metals in consumed fishery products in the Republic of Korea. Environ Sci Pollut Res 27(26):33042\u201333051. https:\/\/doi.org\/10.1007\/s11356-020-09624-0","journal-title":"Environ Sci Pollut Res"},{"issue":"4","key":"4141_CR3","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.3390\/ijms12042336","volume":"12","author":"C Valadez-Vega","year":"2011","unstructured":"Valadez-Vega C, Zuniga-Perez C, Quintanar-Gomez S, Morales-Gonzalez JA, Madrigal-Santillan E, Villagomez-Ibarra JR, Sumaya-Martinez MT, Garcia-Paredes JD (2011) Lead, cadmium and cobalt (Pb, Cd, and Co) leaching of glass-clay containers by pH effect of food. Int J Mol Sci 12(4):2336\u20132350","journal-title":"Int J Mol Sci"},{"issue":"5","key":"4141_CR4","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1271\/bbb.60679","volume":"71","author":"Y Oishi","year":"2007","unstructured":"Oishi Y, Ohnishi M, Ashi-Haiiori KK, Takita T, Noguch T (2007) Cadmium cation increases the production and mRNA levels of insulin-like growth factor-binding protein-1 in HepG2. Biosci Biotechnol Biochem 71(5):1334\u20131337","journal-title":"Biosci Biotechnol Biochem"},{"key":"4141_CR5","doi-asserted-by":"publisher","first-page":"e540","DOI":"10.1038\/cddis.2013.7","volume":"4","author":"S Xu","year":"2013","unstructured":"Xu S, Pi H, Chen Y, Zhang N, Guo P, Lu Y, He M, Xie J, Zhong M, Zhang Y, Yu Z, Zhou Z (2013) Cadmium induced Drp1-dependent mitochondrial fragmentation by disturbing calcium homeostasis in its hepatotoxicity. Cell Death Dis 4:e540","journal-title":"Cell Death Dis"},{"issue":"2","key":"4141_CR6","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1002\/(sici)1099-0461","volume":"14","author":"LE Rikans","year":"2000","unstructured":"Rikans LE, Yamano T (2000) Mechanisms of cadmium-mediated acute hepatotoxicity. J Biochem Mol Toxicol 14(2):110\u2013117. https:\/\/doi.org\/10.1002\/(sici)1099-0461","journal-title":"J Biochem Mol Toxicol"},{"issue":"6","key":"4141_CR7","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1039\/C7MT00024C","volume":"9","author":"S Gao","year":"2017","unstructured":"Gao S, Wang X, Wang S, Zhu S, Rong R, Xu X (2017) Complex effect of zinc oxide nanoparticles on cadmium chloride-induced hepatotoxicity in mice: protective role of metallothionein. Metallomics 9(6):706\u2013714","journal-title":"Metallomics"},{"key":"4141_CR8","doi-asserted-by":"publisher","first-page":"403","DOI":"10.33549\/physiolres.931197","volume":"57","author":"BI Ognjanovi\u0107","year":"2008","unstructured":"Ognjanovi\u0107 BI, Markovi\u0107 SD, Pavlovi\u0107 SZ, \u017dikic RV, \u0160tajn A\u0160, Saici\u0107 ZS (2008) Effect of chronic cadmium exposure on antioxidant defense system in some tissues of rats: protective effect of selenium. Physiol Res 57:403\u2013411","journal-title":"Physiol Res"},{"issue":"1-3","key":"4141_CR9","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s12011-008-8276-7","volume":"129","author":"UE Obioha","year":"2009","unstructured":"Obioha UE, Suru SM, Ola-Mudathir KF, Faremi TY (2009) Hepatoprotective potentials of onion and garlic extracts on cadmium-induced oxidative damage in rats. Biol Trace Elem Res 129(1-3):143\u2013156","journal-title":"Biol Trace Elem Res"},{"issue":"6","key":"4141_CR10","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.5740\/jaoacint.18-0122","volume":"101","author":"Y Zhang","year":"2018","unstructured":"Zhang Y, Bao Z, Ye X, Xie Z, He K, Mergens B, Li W, Yatcilla M, Zheng Q (2018) Chemical investigation of major constituents in Aloe vera leaves and several commercial aloe juice powders. J AOAC Int 101(6):1741\u20131751","journal-title":"J AOAC Int"},{"issue":"1","key":"4141_CR11","doi-asserted-by":"publisher","first-page":"30","DOI":"10.5958\/2321-5844.2017.00004.8","volume":"8","author":"A Gupta","year":"2017","unstructured":"Gupta A, Rarawt S (2017) Clinical importance of aloe vera: review. Research J Topical and Cosmetic Sci 8(1):30\u201339","journal-title":"Research J Topical and Cosmetic Sci"},{"key":"4141_CR12","doi-asserted-by":"crossref","unstructured":"Salehi B, Albayrak S, Antolak H, Kregiel D, Pawlikowska E, Sharifi-Rad M, Uprety Y, Tsouh Fokou PV, Yousef Z, Amiruddin Zakaria Z, Varoni EM, Sharopov F, Martins N, Iriti M, Sharifi-Rad J (2018) Aloe genus plants: from farm to food applications and phytopharmacotherapy. Int J Mol Sci 19(9)","DOI":"10.3390\/ijms19092843"},{"issue":"4","key":"4141_CR13","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1080\/00365521.2018.1447597","volume":"53","author":"B Ahluwalia","year":"2018","unstructured":"Ahluwalia B, Moraes L, Magnusson MK, Ohman L (2018) Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies. Scand J Gastroenterol 53(4):379\u2013389","journal-title":"Scand J Gastroenterol"},{"key":"4141_CR14","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1111\/j.1440-1681.2006.04351.x","volume":"33","author":"S Rajasekaran","year":"2006","unstructured":"Rajasekaran S, Ravi K, Sivagnanam K, Subramanian S (2006) Beneficial effects of aloe vera leaf gel extract on lipid profile status in rats with streptozotocin diabetes. Clin Exp Pharmacol Physiol 33:232\u2013237","journal-title":"Clin Exp Pharmacol Physiol"},{"issue":"1","key":"4141_CR15","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.biocel.2006.07.013","volume":"39","author":"P Murugavel","year":"2007","unstructured":"Murugavel P, Pari L, Sitasawad SL, Kumar S, Kumar S (2007) Cadmium induced mitochondrial injury and apoptosis in vero cells: protective effect of diallyl tetrasufide from garlic. Int J Biochem Cell Biol 39(1):161\u2013170. https:\/\/doi.org\/10.1016\/j.biocel.2006.07.013","journal-title":"Int J Biochem Cell Biol"},{"issue":"3","key":"4141_CR16","doi-asserted-by":"publisher","first-page":"154","DOI":"10.34172\/mejdd.2020.177","volume":"12","author":"N Hassanshahi","year":"2020","unstructured":"Hassanshahi N, Masoumi SJ, Mehrabani D, Hashemi SS, Zare M (2020) The healing effect of Aloe vera gel on acetic acid-induced ulcerative colitis in rat. Middle East J Dig Dis 12(3):154\u2013161. https:\/\/doi.org\/10.34172\/mejdd.2020.177","journal-title":"Middle East J Dig Dis"},{"issue":"2","key":"4141_CR17","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/0026-265X(92)90044-4","volume":"46","author":"D Manca","year":"1992","unstructured":"Manca D, Lefebvre M, Trottier B, Lapar\u00e9 S, Ricard AC, Van Tra H, Chevalier G (1992) Micro method for determination of cadmium in tissues and slurried samples by use of flameless atomic absorption spectrometry. Microchem J 46(2):249\u2013258","journal-title":"Microchem J"},{"issue":"1","key":"4141_CR18","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1006\/niox.2000.0319","volume":"5","author":"KM Miranda","year":"2001","unstructured":"Miranda KM, Espey MG, Wink DA (2001) A rapid simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5(1):62\u201371","journal-title":"Nitric Oxide"},{"issue":"2","key":"4141_CR19","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","volume":"95","author":"H Ohkawa","year":"1979","unstructured":"Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351\u2013358. https:\/\/doi.org\/10.1016\/0003-2697(79)90738-3","journal-title":"Anal Biochem"},{"issue":"6","key":"4141_CR20","doi-asserted-by":"publisher","first-page":"623","DOI":"10.14670\/HH-22.623","volume":"22","author":"D Vyas","year":"2007","unstructured":"Vyas D, Robertson CM, Stromberg PE et al (2007) Epithelial apoptosis in mechanistically distinct methods of injury in the murine small intestine. Histol Histopathol 22(6):623\u2013630. https:\/\/doi.org\/10.14670\/HH-22.623","journal-title":"Histol Histopathol"},{"key":"4141_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/394652","volume":"394652","author":"RA Bernhoft","year":"2013","unstructured":"Bernhoft RA (2013) Cadmium toxicity and treatment. Sci World J 394652:1\u20137. https:\/\/doi.org\/10.1155\/2013\/394652","journal-title":"Sci World J"},{"issue":"2","key":"4141_CR22","doi-asserted-by":"publisher","first-page":"274","DOI":"10.3390\/ijerph16020274","volume":"16","author":"M Andjelkovic","year":"2019","unstructured":"Andjelkovic M, Buha Djordjevic A, Antonijevic E, Antonijevic B, Stanic M, Kotur-Stevuljevic J, Spasojevic-Kalimanovska V, Jovanovic M, BoricicN WD, Bulat Z (2019) Toxic effect of acute cadmium and lead exposure in rat blood, liver, and kidney. Int J Environ Res Public Health 16(2):274. https:\/\/doi.org\/10.3390\/ijerph16020274","journal-title":"Int J Environ Res Public Health"},{"issue":"447","key":"4141_CR23","first-page":"823","volume":"49","author":"B Vogler","year":"1999","unstructured":"Vogler B, Ernst E (1999) Aloe vera: a systematic review of its clinical effectiveness. Br J Gen Pract 49(447):823\u2013828","journal-title":"Br J Gen Pract"},{"issue":"7","key":"4141_CR24","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1007\/s11605-013-2210-9","volume":"17","author":"O Hyder","year":"2013","unstructured":"Hyder O, Chung M, Cosgrove D, Herman JM, Li Z, Firoozmand A, Gurakar A, Koteish A, Pawlik TM (2013) Cadmium exposure and liver disease among US adults. J Gastrointest Surg 17(7):1265\u20131273. https:\/\/doi.org\/10.1007\/s11605-013-2210-9","journal-title":"J Gastrointest Surg"},{"key":"4141_CR25","unstructured":"Argonne National Laboratories, Cadmium, Human Health Fact Sheet, Argonne National Laboratories, Lemont, Ill, USA, 2001."},{"key":"4141_CR26","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/s00128-005-0883-9","volume":"76","author":"E Kobayashi","year":"2006","unstructured":"Kobayashi E, Suwazono Y et al (2006) Tolerable level of lifetime cadmium intake estimated as a benchmark dose low, based on excretion of beta2-Microglobulin in the cadmium-polluted regions of the Kakehashi River Basin, Japan. Bull Environ Contam Toxicol 76:8\u201315","journal-title":"Bull Environ Contam Toxicol"},{"key":"4141_CR27","doi-asserted-by":"publisher","first-page":"129735","DOI":"10.1016\/j.chemosphere.2021.129735","volume":"271","author":"K Renu","year":"2021","unstructured":"Renu K, Chakraborty R, Myakala H, Koti R, Ademola C, Famurewa AC, Madhyastha H, Vellingiri B, George A, Gopalakrishnan AV (2021) Molecular mechanism of heavy metals (lead, chromium, arsenic, mercury, nickel and cadmium)\u2014induced hepatotoxicity\u2014a review. Chemosphere 271:129735. https:\/\/doi.org\/10.1016\/j.chemosphere.2021.129735","journal-title":"Chemosphere"},{"key":"4141_CR28","doi-asserted-by":"publisher","first-page":"3720850","DOI":"10.1155\/2016\/3720850","volume":"2016","author":"U Taukoorah","year":"2016","unstructured":"Taukoorah U, Mahomoodally M (2016) Crude Aloe vera gel shows antioxidant propensities and inhibits pancreatic lipase and glucose movement in vitro. Adv Pharmacol Sci 2016:3720850. https:\/\/doi.org\/10.1155\/2016\/3720850","journal-title":"Adv Pharmacol Sci"},{"key":"4141_CR29","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.2174\/1389450116666150506114336","volume":"17","author":"MM Brz\u00f3ska","year":"2016","unstructured":"Brz\u00f3ska MM, Borowska S, Tomczyk M (2016) Antioxidants as a potential preventive and therapeutic strategy for cadmium. Curr Drug Targets 17:1350\u20131384","journal-title":"Curr Drug Targets"},{"issue":"3","key":"4141_CR30","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1016\/j.indcrop.2013.06.008","volume":"49","author":"A Ray","year":"2013","unstructured":"Ray A, Dutta Gupta S, Ghosh S (2013) Evaluation of anti-oxidative activity and UV absorption potential of the extracts of Aloe vera L. gel from different growth periods of plants. Ind Crop Prod 49(3):712\u2013719. https:\/\/doi.org\/10.1016\/j.indcrop.2013.06.008","journal-title":"Ind Crop Prod"},{"issue":"6","key":"4141_CR31","first-page":"209","volume":"6","author":"PD Whanger","year":"1992","unstructured":"Whanger PD (1992) Selenium in the treatment of heavy metal poisoning and chemical carcinogenesis. J Trace Elem Electrolytes Health Dis 6(6):209\u2013221","journal-title":"J Trace Elem Electrolytes Health Dis"},{"issue":"4","key":"4141_CR32","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1080\/09603123.2013.835032","volume":"24","author":"A Rani","year":"2014","unstructured":"Rani A, Kumar A, Lal A, Pant M (2014) Cellular mechanisms of cadmium-induced toxicity: a review. Int J Environ Health Res 24(4):378\u2013399","journal-title":"Int J Environ Health Res"},{"issue":"3","key":"4141_CR33","doi-asserted-by":"publisher","first-page":"135","DOI":"10.22088\/cjim.8.3.135","volume":"8","author":"RM Rafati","year":"2017","unstructured":"Rafati RM, Kazemi S, Moghadamnia AA (2017) Cadmium toxicity and treatment: an update. Caspian. J Intern Med 8(3):135\u2013145. https:\/\/doi.org\/10.22088\/cjim.8.3.135","journal-title":"J Intern Med"},{"issue":"20","key":"4141_CR34","doi-asserted-by":"publisher","first-page":"12213","DOI":"10.3390\/ijms232012213","volume":"23","author":"R Teschke","year":"2022","unstructured":"Teschke R (2022) Aluminum, arsenic, beryllium, cadmium, chromium, cobalt, copper, iron, lead, mercury, molybdenum, nickel, platinum, thallium, titanium, vanadium, and zinc: molecular aspects in experimental liver injury. Int J Mol Sci 23(20):12213. https:\/\/doi.org\/10.3390\/ijms232012213","journal-title":"Int J Mol Sci"},{"key":"4141_CR35","doi-asserted-by":"publisher","first-page":"471","DOI":"10.2174\/1568010054526359","volume":"4","author":"R Korhonen","year":"2005","unstructured":"Korhonen R, Lahti A, Kankaanranta H, Moilanen E (2005) Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy 4:471\u2013479","journal-title":"Curr Drug Targets Inflamm Allergy"},{"issue":"11","key":"4141_CR36","doi-asserted-by":"publisher","first-page":"26087","DOI":"10.3390\/ijms161125942","volume":"16","author":"S Li","year":"2015","unstructured":"Li S, Tan HY, Wang N, Zhang Z-J, Lao L, Wong C-W, Feng Y (2015) The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci 16(11):26087\u201326124. https:\/\/doi.org\/10.3390\/ijms161125942","journal-title":"Int J Mol Sci"},{"issue":"4","key":"4141_CR37","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.bcp.2004.08.027","volume":"69","author":"LG Costa","year":"2005","unstructured":"Costa LG, Vitalone A, Cole TB, Furlong CE (2005) Modulation of paraoxonase (PON1) activity. Biochem Pharmacol 69(4):541\u2013550","journal-title":"Biochem Pharmacol"},{"key":"4141_CR38","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1007\/s10620-006-9251-9","volume":"52","author":"B Ustundag","year":"2007","unstructured":"Ustundag B, Bahcecioglu IH, Sahin K, Duzgun S, Koca S, Gulcu F, Ozercan IH (2007) Protective effect of soy isoflavones and activity levels of plasma paraoxonase and arylesterase in the experimental nonalcoholic steatohepatitis model. Dig Dis Sci 52:2006\u20132014","journal-title":"Dig Dis Sci"},{"key":"4141_CR39","first-page":"94","volume":"10","author":"C Zhang","year":"2008","unstructured":"Zhang C, Peng W, Jiang X, Chen B, Zhu J, Zang Y, Zhang J, Zhu T, Qin J (2008) Transgene expression of human PON1 Q in mice protects the liver against CCl4 induced injury. J Genet 10:94\u2013100","journal-title":"J Genet"},{"key":"4141_CR40","doi-asserted-by":"publisher","first-page":"26359","DOI":"10.1007\/s11356-021-13687-y","volume":"21","author":"ME Taghavizadeh Yazdi","year":"2021","unstructured":"Taghavizadeh Yazdi ME, Amiri MS, Nourbakhsh F, Rahnama M, Forouzanfar F, Mousavi SH (2021) Bio-indicators in cadmium toxicity: role of HSP27 and HSP70. Environ Sci Pollut Res Int 21:26359\u201326379. https:\/\/doi.org\/10.1007\/s11356-021-13687-y","journal-title":"Environ Sci Pollut Res Int"},{"key":"4141_CR41","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1021\/acs.chemrestox.7b00278","volume":"30","author":"M Akiyama","year":"2017","unstructured":"Akiyama M, Shinkai Y, Unoki T, Shim I, Ishii I, Kumagai Y (2017) The capture of cadmium by reactive polysulfides attenuates cadmium-induced adaptive responses and hepatotoxicity. Chem Res Toxicol 30:2209\u20132217","journal-title":"Chem Res Toxicol"},{"key":"4141_CR42","doi-asserted-by":"publisher","first-page":"2810","DOI":"10.1080\/14786419.2017.1295238","volume":"31","author":"YN Sun","year":"2017","unstructured":"Sun YN, Li W, Lee SH, Jang HD, Ma JY, Kim YH (2017) Antioxidant and anti-osteoporotic effects of anthraquinones and related constituents from the aqueous dissolved Aloe exudates. Nat Prod Res 31:2810\u20132813","journal-title":"Nat Prod Res"},{"key":"4141_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.chemosphere.2020.125858","volume":"249","author":"K Guo","year":"2020","unstructured":"Guo K, Ge J, Zhang C, Lv MW, Zhang Q, Talukder M, Li JL (2020) Cadmium induced cardiac inflammation in chicken (Gallus gallus) via modulating cytochrome P450 systems and Nrf2 mediated antioxidant defense. Chemosphere 249:1\u201310","journal-title":"Chemosphere"},{"key":"4141_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.lfs.2020.118192","volume":"258","author":"W Yu","year":"2020","unstructured":"Yu W, Xu ZP, Gao QQ, Xu Y, Wang B, Dai YT (2020) Protective role of wogonin against cadmium induced testicular toxicity: involvement of antioxidant, anti-inflammatory and anti-apoptotic pathways. Life Sci 258:1\u201315","journal-title":"Life Sci"},{"issue":"11","key":"4141_CR45","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1016\/j.freeradbiomed.2010.09.006","volume":"49","author":"S Reuter","year":"2010","unstructured":"Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer how are they linked? Free Radic Biol Med 49(11):1603\u20131616","journal-title":"Free Radic Biol Med"},{"issue":"7","key":"4141_CR46","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/s41580-020-0230-3","volume":"21","author":"H Sies","year":"2020","unstructured":"Sies H, Jones DP (2020) Reactive oxygen species (ROS) as pleiotropic physiological signaling agents. Nat Rev Mol Cell Biol 21(7):363\u2013383","journal-title":"Nat Rev Mol Cell Biol"},{"key":"4141_CR47","first-page":"24e33","volume":"4","author":"S Roy","year":"2015","unstructured":"Roy S, Benz F, Luedde T, Roderburg C (2015) The role of miRNAs in the regulation of inflammatory processes during hepatofibrogenesis. Hepatobiliary Surg Nutr 4:24e33","journal-title":"Hepatobiliary Surg Nutr"},{"issue":"3","key":"4141_CR48","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1182\/blood-2002-11-3550","volume":"102","author":"Z Estrov","year":"2003","unstructured":"Estrov Z, Shishodia S, Faderl S, Harris D, Van Q, Kantarjian HM, Talpaz M, Aggarwal BB (2003) Resveratrol blocks interleukin-1\u03b2\u2013induced activation of the nuclear transcription factor NF-\u03baB, inhibits proliferation, causes S-phase arrest, and induces apoptosis of acute myeloid leukemia cells. Blood 102(3):987\u2013995","journal-title":"Blood"},{"key":"4141_CR49","doi-asserted-by":"crossref","unstructured":"He Q, Luo XZ (2021) Sulforaphane ameliorates cadmium induced hepatotoxicity through the up-regulation of \/Nrf2\/ARE pathway and the inactivation of NF-\u03baB. J Funct Foods 77","DOI":"10.1016\/j.jff.2020.104297"},{"key":"4141_CR50","doi-asserted-by":"publisher","first-page":"18329","DOI":"10.1002\/jcp.28466","volume":"234","author":"VK Gupta","year":"2019","unstructured":"Gupta VK, Siddiqi NJ, Ojha AK, Sharma B (2019) Hepatoprotective effect of Aloe vera against cartap- and malathion-induced toxicity in Wistar rats. J Cell Physiol 234:18329\u201318343","journal-title":"J Cell Physiol"},{"key":"4141_CR51","first-page":"2645","volume":"35","author":"O Kadioglu","year":"2015","unstructured":"Kadioglu O, Nass J, Saeed MEM, Schuler B, Efferth T (2015) Kaempferol is an anti-inflammatory compound with activity towards NF-\u03baB pathway proteins. Anticancer Res 35:2645\u20132650","journal-title":"Anticancer Res"},{"issue":"4","key":"4141_CR52","doi-asserted-by":"publisher","first-page":"35","DOI":"10.31142\/ijtsrd23541","volume":"3","author":"AJ Pegu","year":"2019","unstructured":"Pegu AJ, Shaema A (2019) Review on Aloe vera. International Journal of Trend in Scientific Research and Development 3(4):35\u201340","journal-title":"International Journal of Trend in Scientific Research and Development"},{"issue":"2","key":"4141_CR53","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1007\/s12011-019-01860-x","volume":"195","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, Chang Y, Yang T, Wen M, Zhang Z, Liu G et al (2020) The hepatoprotective effects of zinc glycine on liver injury in meat duck through alleviating hepatic lipid deposition and inflammation. Biol Trace Elem Res 195(2):569\u2013578","journal-title":"Biol Trace Elem Res"},{"issue":"6","key":"4141_CR54","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.3390\/molecules25061324","volume":"25","author":"M S\u00e1nchez","year":"2020","unstructured":"S\u00e1nchez M, Gonz\u00e1lez-Burgos E, Iglesias I, G\u00f3mez-Serranillos MP (2020) Pharmacological update properties of Aloe vera and its major active constituents. Molecules 25(6):1324. https:\/\/doi.org\/10.3390\/molecules25061324","journal-title":"Molecules"},{"key":"4141_CR55","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1016\/j.ijbiomac","volume":"159","author":"Y Zhao","year":"2020","unstructured":"Zhao Y, Jayachandran M, Xu B (2020) In vivo antioxidant and anti-inflammatory effects of soluble dietary fiber Konjac glucomannan in type-2 diabetic rats. Int J Biol Macromol 159:1186\u20131196. https:\/\/doi.org\/10.1016\/j.ijbiomac","journal-title":"Int J Biol Macromol"},{"key":"4141_CR56","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.addr.2017.05.016","volume":"121","author":"K B\u00f6ttcher","year":"2017","unstructured":"B\u00f6ttcher K, Pinzani M (2017) Pathophysiology of liver fibrosis and the methodological barriers to the development of anti-fibrogenic agents. Adv Drug Deliv Rev 121:3\u20138. https:\/\/doi.org\/10.1016\/j.addr.2017.05.016","journal-title":"Adv Drug Deliv Rev"},{"key":"4141_CR57","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","volume":"14","author":"T Suchida","year":"2017","unstructured":"Suchida T, Friedman S (2017) Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol 14:397\u2013411. https:\/\/doi.org\/10.1038\/nrgastro.2017.38","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"5","key":"4141_CR58","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.3390\/cells9051212","volume":"9","author":"E Geervliet","year":"2020","unstructured":"Geervliet E, Bansal R (2020) Matrix metalloproteinases as potential biomarkers and therapeutic targets in liver diseases. Cells 9(5):1212","journal-title":"Cells"},{"key":"4141_CR59","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.tox.2015.10.008","volume":"338","author":"S Lian","year":"2015","unstructured":"Lian S, Xia Y, Khoi PN, Ung TT, Yoon HJ, Kim NH, Kim KK, Jung YD (2015) Cadmium induces matrix metalloproteinase-9 expression via ROS-dependent EGFR, NF-kB, and AP-1 pathways in human endothelial cells. Toxicology 338:104\u2013116","journal-title":"Toxicology"},{"key":"4141_CR60","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1080\/2162402X.2016.1202390","volume":"5","author":"D Hendriks","year":"2016","unstructured":"Hendriks D, He Y, Koopmans I, Wiersma VR, van Ginkel RJ, Samplonius DF, Helfrich W, Bremer E (2016) Programmed death ligand 1 (PD-L1)-targeted TRAIL combines PD-L1-mediated checkpoint inhibition with TRAIL-mediated apoptosis induction. OncoImmunology 5:8. https:\/\/doi.org\/10.1080\/2162402X.2016.1202390","journal-title":"OncoImmunology"},{"key":"4141_CR61","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s13287-019-1177-1","volume":"10","author":"J Jin","year":"2019","unstructured":"Jin J, Shi Y, Gong J et al (2019) Exosome secreted from adipose-derived stem cells attenuates diabetic nephropathy by promoting autophagy flux and inhibiting apoptosis in podocyte. Stem Cell Res Ther 10:95. https:\/\/doi.org\/10.1186\/s13287-019-1177-1","journal-title":"Stem Cell Res Ther"},{"key":"4141_CR62","first-page":"2033","volume":"43","author":"G Luo","year":"2019","unstructured":"Luo G, Jian Z, Zhu Y, Zhu Y, Chen B, Ma R, Tang F, Xiao Y (2019) Sirt1 promotes autophagy and inhibits apoptosis to protect cardiomyocytes from hypoxic stress. Int J Mol Med 43:2033\u20132043","journal-title":"Int J Mol Med"},{"issue":"6","key":"4141_CR63","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1021\/bm060154s","volume":"7","author":"T Saito","year":"2006","unstructured":"Saito T, Nishiyama Y, Putaux JL, Vignon M, Isogai A (2006) Homogeneous suspensions of individualized microfibrils from TEMPO-catalyzed oxidation of native cellulose. Biomacromolecules 7(6):1687\u20131691. https:\/\/doi.org\/10.1021\/bm060154s","journal-title":"Biomacromolecules"},{"issue":"2022","key":"4141_CR64","doi-asserted-by":"publisher","first-page":"5463134","DOI":"10.1155\/2022\/5463134","volume":"5","author":"Z Huang","year":"2022","unstructured":"Huang Z, Han J, Wu P, Wu C, Fan Y, Zhao L, Hao X, Chen D, Zhu M (2022) Sorting nexin 5 plays an important role in promoting ferroptosis in Parkinson\u2019s disease. Oxidative Med Cell Longev 5(2022):5463134. https:\/\/doi.org\/10.1155\/2022\/5463134","journal-title":"Oxidative Med Cell Longev"},{"key":"4141_CR65","doi-asserted-by":"publisher","first-page":"102021","DOI":"10.1016\/j.redox.2021.102021","volume":"45","author":"S Jang","year":"2021","unstructured":"Jang S, Chapa-Dubocq XR, Tyurina YY, St Croix CM, Kapralov AA, Tyurin VA, Bay\u0131r H, Kagan VE, Javadov S (2021) Elucidating the contribution of mitochondrial glutathione to ferroptosis in cardiomyocytes. Redox Biol 45:102021. https:\/\/doi.org\/10.1016\/j.redox.2021.102021","journal-title":"Redox Biol"},{"key":"4141_CR66","doi-asserted-by":"publisher","unstructured":"Cai J, Guan H, Jiao X, Yang J, Chen X, Zhang H, Zheng Y, Zhu Y, Liu Q, Zhang Z (2021) NLRP3 inflammasome mediated pyroptosis is involved in cadmium exposure-induced neuroinflammation through the IL-1\u03b2\/IkB-\u03b1-NF-\u03baB-NLRP3 feedback loop in swine. Toxicology. 453. https:\/\/doi.org\/10.1016\/j.tox.2021.152720","DOI":"10.1016\/j.tox.2021.152720"},{"key":"4141_CR67","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.intimp.2017.09.022","volume":"52","author":"Z Peng","year":"2017","unstructured":"Peng Z, Gong X, Yang Y, Huang L, Zhang Q, Zhang P, Wan R, Zhang B (2017) Hepatoprotective effect of quercetin against LPS\/d-GalN induced acute liver injury in mice by inhibiting the IKK\/NF-\u03baB and MAPK signal pathways. Int Immunopharmacol 52:281\u2013289","journal-title":"Int Immunopharmacol"},{"key":"4141_CR68","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.lfs.2018.07.017","volume":"208","author":"NH Zaidun","year":"2018","unstructured":"Zaidun NH, Thent ZC, Latiff AA (2018) Combating oxidative stress disorders with citrus flavonoid: naringenin. Life Sci 208:111\u2013122","journal-title":"Life Sci"},{"key":"4141_CR69","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1080\/13880209.2021.1877734","volume":"59","author":"MN BinMowyna","year":"2021","unstructured":"BinMowyna MN, AlFaris NA (2021) Kaempferol suppresses acetaminophen-induced liver damage by upregulation\/activation of SIRT1. Pharm Biol 59:146\u2013156","journal-title":"Pharm Biol"},{"key":"4141_CR70","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s11010-020-03885-6","volume":"476","author":"P Rajendran","year":"2021","unstructured":"Rajendran P, Maheshwari U, Muthukrishnan A, Muthuswamy R, Anand K, Ravindran B, Dhanaraj P, Balamuralikrishnan B, Chang SW, Chung WJ (2021) Myricetin: versatile plant-based flavonoid for cancer treatment by inducing cell cycle arrest and ROS\u2013reliant mitochondria-facilitated apoptosis in A549 lung cancer cells and in silico prediction. Mol Cell Biochem 476:57\u201368","journal-title":"Mol Cell Biochem"},{"issue":"2","key":"4141_CR71","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1002\/ptr.6532","volume":"34","author":"X Dong","year":"2020","unstructured":"Dong X, Zeng Y, Liu Y, You L, Yin X, Fu J, Ni J (2020) Aloe-emodin: a review of its pharmacology, toxicity, and pharmacokinetics. Phytother Res 34(2):270\u2013281","journal-title":"Phytother Res"}],"container-title":["Biological Trace Element Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12011-024-04141-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12011-024-04141-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12011-024-04141-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T05:29:23Z","timestamp":1736141363000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12011-024-04141-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,12]]},"references-count":71,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["4141"],"URL":"https:\/\/doi.org\/10.1007\/s12011-024-04141-4","relation":{},"ISSN":["0163-4984","1559-0720"],"issn-type":[{"value":"0163-4984","type":"print"},{"value":"1559-0720","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,12]]},"assertion":[{"value":"28 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Animals were used as study subjects. With the approval of the regional institutional animal ethics committee, all stated methods and the handling of animals were carried out in accordance with the standards set out by the Ethical Committee for Animal Studies of the Faculty of Science, Ain Shams University <b>(approval code: ASU-SCI\/BIOC\/2023\/2\/2).<\/b>","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Not applicable since the research was not conducted on humans.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable since our research was not conducted on human subjects.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"\u201cThe authors have no relevant financial or non-financial interests to disclose.\u201d","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}