Subclinical Renal Toxicity of Monosodium Glutamate : A Dose–Response Histopathology Study in Rattus norvegicus
Abstract
Monosodium glutamate (MSG) is commonly used as a flavor enhancer; nevertheless, evidence of early, subclinical kidney damage from short-term oral exposure is scarce. This study assessed dose-dependent proximal tubular damage and its correlation with macroscopic renal observations after graded MSG delivery in rats. Sixteen male Wistar rats were randomly assigned to four groups (n = 4/group): a control group and three groups receiving monosodium glutamate (MSG) at doses of approximately 750, 1500, or 2250 mg/kg/day (MSG750, MSG1500, MSG2250) through oral gavage for a duration of 14 days. Post-necropsy, the kidneys were evaluated macroscopically (kidney weight index, linear dimensions, gross lesions) and histologically. Proximal tubular epithelial cells were enumerated in 20 non-overlapping cortical high-power fields (HPFs) per rat and classified as normal, degenerative, or necrotic; the counts were aggregated to obtain the total number of cells per 20 HPFs. Group disparities were assessed utilizing one-way ANOVA accompanied by Tukey’s post-hoc analyses. The macroscopic appearance, kidney weight index, and renal dimensions were consistent between groups (all p > 0.05). Conversely, histology revealed a pronounced dose–response relationship: normal tubular cell counts diminished progressively, whereas degenerative and necrotic cell counts increased significantly with escalating MSG doses (overall one-way ANOVA, p < 0.01).The highest-dose group demonstrated significant tubular degeneration and necrosis, despite maintaining general morphological integrity. In summary, short-term high-dose oral MSG causes significant, dose-dependent harm to the proximal tubules, which may not be evident upon gross inspection, indicating that the proximal tubule is an early and sensitive target in MSG-related nephrotoxicity.
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References
- 1. Yu H, Wang R, Zhao Y, et al. Monosodium Glutamate Intake and Risk Assessment in China Nationwide, and a Comparative Analysis Worldwide. Nutrients. 2023;15(11):2444. doi:10.3390/nu15112444
- 2. Morita R, Ohta M, Hayabuchi H. PS-P14-1: Effect Of Monosodium Glutamate On Dietary Salt Reduction In Female Students From East And Southeast Asia: An International Comparison. Journal of Hypertension. 2023;41(Suppl 1):e498. doi:10.1097/01.hjh.0000918004.24516.a6
- 3. Ramadhani A, Sofro ZM, Partadiredja G. The effect of oral administration of monosodium glutamate on orofacial pain response and the estimated number of trigeminal ganglion sensory neurons of male Wistar rats. Gunadi, Yamada T, Pramana AAC, et al., eds. BIO Web of Conferences. 2021;41:05007. doi:10.1051/bioconf/20214105007
- 4. Žakauskienė U, Sukackienė D, Mačionienė E, et al. Ps-P14-2: Arterial Hypertension and Salt Consumption in Lithuania. Journal of Hypertension. 2023;41(Suppl 1):e498. doi:10.1097/01.hjh.0000918008.16473.be
- 5. Farhood zainab H, Eltayef E mahmoud, Madlool ZS. Biochemical Assessment of Hepatic and Renal Functions Following Administration of Doses of Monosodium Glutamate and Shilajit in Albino Mice. Preprint posted online June 20, 2025. doi:10.21203/rs.3.rs-6710430/v1
- 6. Kassab RB, Theyab A, Al-Ghamdy AO, et al. Protocatechuic Acid Abrogates Oxidative Insults, Inflammation and Apoptosis in Liver and Kidney Associated With Monosodium Glutamate Intoxication in Rats. Environmental Science and Pollution Research. 2021;29(8):12208-12221. doi:10.21203/rs.3.rs-731074/v1
- 7. Koohpeyma F, Siri M, Allahyari S, Mahmoodi M, Saki F, Dastghaib S. The effects of L-carnitine on renal function and gene expression of caspase-9 and Bcl-2 in monosodium glutamate‐induced rats. BMC Nephrology. 2021;22(1):162. doi:10.1186/s12882-021-02364-4
- 8. Elmas MA, Özgün G, Özakpınar ÖB, Güleken Z, Arbak S. Effects of Apocynin Against Monosodium Glutamate-Induced Oxidative Damage in Rat Kidne. European Journal of Biology. 2022;0(0):0. doi:10.26650/eurjbiol.2022.1148934
- 9. Abd‐Elkareem M, Soliman M, El‐Rahman MAMA, Khalil NSA. Effect of Nigella Sativa L. Seed on the Kidney of Monosodium Glutamate Challenged Rats. Frontiers in Pharmacology. 2022;13. doi:10.3389/fphar.2022.789988
- 10. Rahajeng ADR, Rahmatullah AA, Putri CEA, et al. Nephroprotective Effect of Dayak Onion (Eleutherine palmifolia) Against Monosodium Glutamate-Induced Renal Toxicity in Mice (Mus musculus). Journal of Applied Veterinary Science And Technology. 2024;5(2):129-134. doi:10.20473/javest.V5.I2.2024.129-134
- 11. Uroko R, Agbafor A, Egba S, Nwuke C, Kalu-Kalu S. Evaluation of antioxidant activities and haematological effects of Asystasia gangetica leaf extract in monosodium glutamate-treated rats. Lekovite sirovine. 2021;41(1):5-11. doi:10.5937/leksir2141005U
- 12. ALhamed TA, Farah A. Al-marzook, Al-Asady AM. The harmful Effects of Monosodium Glutamate on Blood Parameters Liver and Kidney Functions In Adult White Rats and the Protective Role of Omega-3. Indian Journal of Forensic Medicine & Toxicology. 2021;15(3):5245-5250. doi:10.37506/ijfmt.v15i3.16266
- 13. Celestino M, Balmaceda Valdez V, Brun P, Castagliuolo I, Mucignat-Caretta C. Differential effects of sodium chloride and monosodium glutamate on kidney of adult and aging mice. Scientific Reports. 2021;11(1):481. doi:10.1038/s41598-020-80048-z
- 14. Egbuonu ACC, Alaebo PO, Uchukwu CN, et al. Therapeutic Artemether-Lumefantrine Modulated Monosodium Glutamate-Related Adversity on Rats’ Kidney Histology and Antioxidant Response Bio-Indicators. Journal of Applied Sciences and Environmental Management. 2021;25(5):807-814. doi:10.4314/jasem.v25i5.18
- 15. Tosun H, Karadas H, Ceylan H. Bioinformatics‐based identification of hepatocellular carcinoma‐associated hub genes and assessment of the restorative effect of tannic acid in rat liver exposed to monosodium glutamate. Cancer Medicine. 2024;13(12). doi:10.1002/cam4.7404
- 16. Thangachi SB, Mokhashi VS, Murthuza AA. Analysis Of Oxidative Stress Markers In Chronic Consumption Of Monosodium Glutamate On Liver Of Wistar Albino Rats. Asian Journal of Pharmaceutical and Clinical Research. Published online November 7, 2021:116-119. doi:10.22159/ajpcr.2021.v14i11.43103
- 17. Ibiyeye R, Imam A, Adana M, Sulaimon F, Ajao M. NR2B-DAPK1-P53 mediated hippocampal cell death following monosodium glutamate ingestion and interventions with luteolin, caffeic-acid and phoenix dactylifera. Nepal Journal of Neuroscience. 2022;19(3):3-8. doi:10.3126/njn.v19i3.47346
- 18. Bölükbaş F. Histopathological and Immunohistochemical Study to Determine the Effects of Monosodium Glutamate on Skeletal Muscle Development in Chickens. Kocatepe Veterinary Journal. Published online 2023. doi:10.30607/kvj.1223940
- 19. Liang J, Liu Y. Animal Models of Kidney Disease: Challenges and Perspectives. Kidney360. 2023;4(10):1479-1493. doi:10.34067/KID.0000000000000227
- 20. Dimov N, Yaneva A, Valcheva E, et al. Biomarkers for Early Detection of Cisplatin-Induced Nephrotoxicity. Life. 2025;15(9):1432. doi:10.3390/life15091432
- 21. McMahon KR, Chui H, Rassekh SR, et al. Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury. Kidney360. 2022;3(1):37-50. doi:10.34067/KID.0004802021
- 22. Miloševski‐Lomić G, Kotur‐Stevuljević J, Paripović D, et al. Integrated Urinary Biomarkers Can Predict Early Acute Kidney Injury in Children Undergoing Chemotherapy. Published online 2023. doi:10.21203/rs.3.rs-3546589/v1
- 23. Roy D, Kulkarni A, Chaudhary M, Chaudhary S, Payasi A, Aggarwal A. Polymyxin B-Induced Kidney Injury Assessment of a Novel Formulation of Polymyxin B (VRP-034) in Rats. Antibiotics. 2021;10(4):359. doi:10.3390/antibiotics10040359
- 24. Pavitrakar VN, Mody R, Ravindran S. Protective effects of recombinant human golimumab and pentoxifylline in nephrotoxicity induced by cisplatin. Journal of Biochemical and Molecular Toxicology. 2022;36(4). doi:10.1002/jbt.22990
- 25. Kook MS, Kim H, Choi Y, Bae SM, Yu J, Kim YS. The α-Helical Amphipathic Peptide Alleviates Colistin-Induced Nephrotoxicity by Maintaining Mitochondrial Function in Both In Vitro and In Vivo Infection Models. Antibiotics. 2025;14(5):445. doi:10.3390/antibiotics14050445
- 26. Manhar N, Singh SK, Yadav P, et al. Methyl Donor Ameliorates CCl 4 ‐Induced Nephrotoxicity by Inhibiting Oxidative Stress, Inflammation, and Fibrosis Through the Attenuation of Kidney Injury Molecule 1 and Neutrophil Gelatinase‐Associated Lipocalin Expression. Journal of Biochemical and Molecular Toxicology. 2025;39(3). doi:10.1002/jbt.70188
- 27. Ijaz MU, Majeed SA, Asharaf A, et al. Toxicological effects of thimerosal on rat kidney: a histological and biochemical study. Brazilian Journal of Biology. 2023;83. doi:10.1590/1519-6984.242942
- 28. Muğlu H, İnan Kahraman E, Sünger E, Murt A, Bilici A, Görgülü N. Acute Kidney Injury Secondary to Abdominal Compartment Syndrome: Biomarkers, Pressure Variability, and Clinical Outcomes. Medicina. 2025;61(3):383. doi:10.3390/medicina61030383
- 29. Egbuonu ACC, Alaebo PO, Obike CA, et al. Antioxidant and Nephroprotective Studies on Telfairia occidentalis Pod in Experimental Rats. Nigerian Journal of Biochemistry and Molecular Biology. 2024;39(2):99-105. doi:10.4314/njbmb.v39i2.9
- 30. Mahmoud HS, Kamel EM, Gad EL-Hak HN, et al. Potential Ameliorative Effect of Crude Honeybee on Monosodium Glutamate Induced Nephrotoxicity to Male Rats. The Egyptian Journal of Hospital Medicine. 2022;89(2):7719-7726. doi:10.21608/ejhm.2022.277126
- 31. Slima S, Ragab R. Protective Effect of Curcumin Against Monosodium Glutamate-Induced Oxidative Renal Damage: biochemical and histopathological study Received in original form: 23 September 2022 Accepted finally: 5 December 2022. Ain Shams Journal of Forensic Medicine and Clinical Toxicology. 2023;40(1):66-73. doi:10.21608/ajfm.2023.281729
- 32. Moldovan OL, Vari CE, Tero-Vescan A, et al. Potential Defence Mechanisms Triggered by Monosodium Glutamate Sub-Chronic Consumption in Two-Year-Old Wistar Rats. Nutrients. 2023;15(20):4436. doi:10.3390/nu15204436
- 33. Nahok K, Phetcharaburanin J, Li J V, et al. Monosodium Glutamate Induces Changes in Hepatic and Renal Metabolic Profiles and Gut Microbiome of Wistar Rats. Nutrients. 2021;13(6):1865. doi:10.3390/nu13061865
- 34. Sukmak M, Kyaw TS, Nahok K, et al. Urinary metabolic profile and its predictive indexes after MSG consumption in rat. Shakaib M, ed. PLOS ONE. 2024;19(9):e0309728. doi:10.1371/journal.pone.0309728
- 35. Banerjee A, Mukherjee S, Maji BK. Monosodium glutamate causes hepato-cardiac derangement in male rats. Human & Experimental Toxicology. 2021;40(12_suppl):S359-S369. doi:10.1177/09603271211049550
- 36. Balaha MF, Alamer AA, Eisa AA, Aljohani HM. Shikonin Alleviates Gentamicin-Induced Renal Injury in Rats by Targeting Renal Endocytosis, SIRT1/Nrf2/HO-1, TLR-4/NF-κB/MAPK, and PI3K/Akt Cascades. Antibiotics. 2023;12(5):826. doi:10.3390/antibiotics12050826
- 37. Aboelwafa HR, Ramadan RA, Ibraheim SS, Yousef HN. Modulation Effects of Eugenol on Nephrotoxicity Triggered by Silver Nanoparticles in Adult Rats. Biology. 2022;11(12):1719. doi:10.3390/biology11121719
- 38. Sandhiutami NMD, Desmiaty Y, Pitaloka PDU, Salsabila S. The protective effect of hydroalcoholic Citrus aurantifolia peel extract against doxorubicin-induced nephrotoxicity. Research in Pharmaceutical Sciences. 2024;19(5):591-605. doi:10.4103/RPS.RPS_99_23
- 39. Ahmed YH, El-Naggar ME, Rashad MM, M.Youssef A, Galal MK, Bashir DW. Screening for polystyrene nanoparticle toxicity on kidneys of adult male albino rats using histopathological, biochemical, and molecular examination results. Cell and Tissue Research. 2022;388(1):149-165. doi:10.1007/s00441-022-03581-5
- 40. Ryabova Y V, Minigalieva IA, Sutunkova MP, et al. Toxic Kidney Damage in Rats Following Subchronic Intraperitoneal Exposure to Element Oxide Nanoparticles. Toxics. 2023;11(9):791. doi:10.3390/toxics11090791
- 41. Pei Z, Wu M, Yu H, et al. Isoliquiritin Ameliorates Cisplatin-Induced Renal Proximal Tubular Cell Injury by Antagonizing Apoptosis, Oxidative Stress and Inflammation. Frontiers in Medicine. 2022;9. doi:10.3389/fmed.2022.873739
- 42. Upadhyay R, Batuman V. Aristolochic acid I induces proximal tubule injury through ROS/HMGB1/mt DNA mediated activation of TLRs. Journal of Cellular and Molecular Medicine. 2022;26(15):4277-4291. doi:10.1111/jcmm.17451
- 43. Brand A, Bokkers B, Biesebeek JD t., Mengelers M. Combined Exposure to Multiple Mycotoxins: An Example of Using a Tiered Approach in a Mixture Risk Assessment. Toxins. 2022;14(5):303. doi:10.3390/toxins14050303
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