Research Article
Year 2025,
Volume: 72 Issue: 2, 211 - 217, 01.04.2025
Abstract
Project Number
Project number 2019/053.
References
- Abd-Elhakim YM, Mohamed WAM, El Bohi KM, et al (2021): Prevention of melamine-induced hepatorenal impairment by an ethanolic extract of Moringa oleifera: Changes in KIM-1, TIMP-1, oxidative stress, apoptosis, and inflammation-related genes. Gene, 764, 145083.
- Allameh A, Niayesh-Mehr R, Aliarab A, et al (2023): Oxidative Stress in Liver Pathophysiology and Disease. Antioxidants (Basel), 22, 1653.
- Ahmed ZSO, Galal MK, Drweesh EA, et al (2021): Protective effect of starch-stabilized selenium nanoparticles against melamine-induced hepato-renal toxicity in male albino rats. Int J Biol Macromol., 30;191:792-802.
- An L, Fu J, Zhang T (2015): Reversible effects of vitamins C and E combination on cognitive deficits and oxidative stress in the hippocampus of melamine-exposed rats. Pharmacol Biochem Behav, 132, 152-159.
- Asadi M, Taghizadeh S, Kaviani E, et al (2022): Caspase-3: Structure, function, and biotechnological aspects. Biotechnol Appl Bioc, 69:1633–1645.
- Buur JL, Baynes RE, Riviere JE (2008): Estimating meat withdrawal times in pigs exposed to melamine contaminated feed using a physiologically based pharmacokinetic model. Regul Toxicol Pharmacol, 51, 324-331.
- Chang L, Wu Q, She R, et al (2021): The pathologic lesions of liver caused by melamine alone or in combination with cyanuric acid in mice. Res Vet Sci, 136, 230-238.
- Chen HC, Feng WW, Audira G, et al (2024): Evaluation of sub-chronic toxicity of melamine via systematic or oral delivery in adult zebrafish based on behavioral endpoints. NeuroToxicology, 102, 68-80.
- Choi BE, Shin S, Evans S, et al (2023): Ablation of TRPC3 disrupts Ca2+ signaling in salivary ductal cells and promotes sialolithiasis. Sci Rep., 13, 5772.
- Cory S, Adams JM (2002): The Bcl-2 family: Regulators of the cellular life-or-death switch. Nat Rev Cancer, 2, 647-656.
- Dalal R, Goldfarb D (2011): Melamine-related kidney stones and renal toxicity. Nat Rev Nephrol., 7, 267–274.
- Delbridge ARD, Strasser A (2015): The BCL-2 protein family, BH3-mimetics, and cancer therapy. Cell Death Differ, 22, 1071-1080.
- Devrim AK, Sozmen M, Devrim T, et al (2017): Periostin normalizes levels of cardiac markers in rats with experimental isoproterenol cardiotoxicity. Bratisl Med J, 118, 705–709.
- Devrim T, Ekici H, Devrim AK, et al (2020): Late effects of cutaneous 3-methylcholanthrene exposure on DNA damage-related pleiotropic growth factors and oxidative stress markers in mice. Bratisl Lek Listy, 121, 325-330.
- Dharnidharka VR (2009): Melamine-contaminated powdered formula and urolithiasis. N Engl J Med, 360, 2676-8.
- Erisgin Z, Mutlu HS, Tekelioglu Y, et al (2021): Hepatotoxic effects of melamine exposure from the weaning period in rats: a flow cytometric, electron microscopic, and histopathologic study. Toxicol Res, 10, 418-424.
- Ganji L, Alebouyeh M, Shirazi MH, et al (2019): Comparative transcriptional analysis for Toll-like receptors, inflammatory cytokines, and apoptotic genes in response to different cytolethal-encoding and noncoding isolates of Salmonella enterica and Campylobacter jejuni from food and human stool. Microb Pathog, 133, 103550.
- Gupta PK (2020): In: Problem Solving Questions in Toxicology: Target Organ Toxicity. Springer, Cham, 83, 117.
- Habotta OA, Abdeen A, Roomi AB, et al (2023): Nootkatone Mitigated Melamine-Evoked Hepatotoxicity by Featuring Oxidative Stress and Inflammation Interconnected Mechanisms: In Vivo and In Silico Approaches. Toxics, 11, 784.
- Huang J, Yang G, Xia F, et al (2018): Reproductive toxicity of melamine against male mice and the related mechanism. Toxicol Mech Methods, 28, 345-352.
- Kintz H, Nylen E, Barber A (2020): Inclusion of Dap10 or 4-1BB costimulation domains in the chPD1 receptor enhances anti-tumor efficacy of T cells in murine models of lymphoma and melanoma. Cell Immunol, 351, 104069.
- Le Na NT, Duc Loc S, Minh Tri NL, et al (2019): Nanomelanin potentially protects the spleen from radiotherapy-associated damage and enhances immunoactivity in tumor-bearing mice. Materials, 12, 1725.
- Mbazima VG, Mokgotho MP, February F, et al (2018): Cellular and molecular mechanism associated with anticancer activity of Commelina benghalensis. Int J Histol Cytol, 5, 415-422.
- Menzie-Suderam JM, Mohammad-Gharibani P, Modi J, et al (2018): Granulocyte-colony stimulating factor protects against endoplasmic reticulum stress in an experimental model of stroke. Brain Res, 1682, 1-13.
- Ramalho RM, Cortez-Pinto H, Castro RE, et al (2006): Apoptosis and Bcl-2 expression in the livers of patients with steatohepatitis. Eur J Gastroenterol Hepatol, 18, 21-29.
- Sak S, Uyanikoglu H, Incebiyik A, et al (2018): Associations of serum fetuin-A and oxidative stress parameters with polycystic ovary syndrome. Clin Exp Reprod Med, 45, 116–121.
- Sharma S, Varsha KK, Kumari S, et al (2020): Acute toxicity analysis of Disarib, an inhibitor of BCL2. Scientific Rep, 10, 15188.
- Shojaie L, Bogdanov JM, Alavifard H, et al (2024): Innate and adaptive immune cell interaction drives inflammasome activation and hepatocyte apoptosis in murine liver injury from immune checkpoint inhibitors. Cell Death Dis, 15, 140.
- Siddiqui WA, Ahad A, Ahsan H (2015): The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update. Arch Toxicol, 89, 289-317.
- Sonobe A, Jesmi, S, Shimojo N, et al (2015): Concomitant down-regulation of Et1-Etb system and VEGF angiogenic signaling in the frontal cortex of endotoxemic mice: A heightened vulnerability to cerebral microcirculation in sepsis. J Vasc Med Surg, 3, 2-7.
- Tessoulin B, Papin A, Gomez-Bougie P, et al (2019): BCL2-family dysregulation in B-cell malignancies: from gene expression regulation to a targeted therapy biomarker. Front Oncol, 8, 645.
- Tsujimoto Y (2002): Bcl-2 family of proteins: life-or-death switch in mitochondria. Biosci Rep, 22, 47-58.
- Wan S, Wang X, Chen W, et al (2024): Exposure to high dose of polystyrene nanoplastics causes trophoblast cell apoptosis and induces miscarriage. Part Fibre Toxicol, 21,13.
- Victorino F, Bigley T, Park E, et al (2021): HIF1α is required for NK cell metabolic adaptation during virus infection. Elife, 10, e68484.
- Yin RH, Wang XZ, Bai WL, et al (2013): The reproductive toxicity of melamine in the absence and presence of cyanuric acid in male mice. Res Vet Sci, 94, 618-627.
- Zhao M, Zhang NX, Economou M, et al (1994): Immunohistochemical detection of bcl-2 protein in liver lesions: bcl-2 protein is expressed in hepatocellular carcinomas but not in liver cell dysplasia. Histopathology, 25, 237-245.
Impact of melamine exposure on apoptotic proteins and oxidative stress markers in mouse hepatic tissue
Abstract
Most melamine studies have focused on renal toxicity and its effects on the liver are still not well known. We investigated the apoptotic and oxidative effects of melamine on the liver using thirty BALB/c mice, divided into three groups. The control group received saline, while the low-dose melamine (LDM) group was given 400 mg/kg (1/8 LD50) and the high-dose melamine (HDM) group received 1600 mg/kg (1/2 LD50) intragastrically (0.25 ml) for 5 consecutive days. Liver Bcl-2 and caspase-3 expressions were analyzed at the protein level by immunohistochemistry and ELISA, and also at the gene level by quantitative Real-Time PCR. In addition, total antioxidant (TAS), total oxidant (TOS), and oxidative stress index (OSI) levels in liver tissues were measured spectrophotometrically. The immunohistochemical expression of caspase-3 was higher in the LDM and HDM groups compared to the control group (p = 0.002). TOS and OSI levels were increased significantly (P <0.05) in the HDM group as compared to controls. Bcl-2 ELISA levels in the HDM group increased significantly compared to the control (P = 0.0024). Caspase-3 values increased significantly in the HDM group compared to the control (P < 0.0001) and LDM (P = 0.0016) groups. This study provides evidence that exposure to melamine induces oxidative stress and increases apoptosis in the liver. In conclusion, we suggest that both apoptotic and anti-apoptotic mechanisms may be disrupted at high melamine exposures, which has not been reported extensively in previous publications.
Keywords
Ethical Statement
This study was carried out after the animal experiment was approved by Kırıkkale University Local Ethics Committee (Decision number: 2018-18.09/47).
Supporting Institution
This work was supported by the Scientific Research Projects Coordination Unit of Kırıkkale University.
Project Number
Project number 2019/053.
References
- Abd-Elhakim YM, Mohamed WAM, El Bohi KM, et al (2021): Prevention of melamine-induced hepatorenal impairment by an ethanolic extract of Moringa oleifera: Changes in KIM-1, TIMP-1, oxidative stress, apoptosis, and inflammation-related genes. Gene, 764, 145083.
- Allameh A, Niayesh-Mehr R, Aliarab A, et al (2023): Oxidative Stress in Liver Pathophysiology and Disease. Antioxidants (Basel), 22, 1653.
- Ahmed ZSO, Galal MK, Drweesh EA, et al (2021): Protective effect of starch-stabilized selenium nanoparticles against melamine-induced hepato-renal toxicity in male albino rats. Int J Biol Macromol., 30;191:792-802.
- An L, Fu J, Zhang T (2015): Reversible effects of vitamins C and E combination on cognitive deficits and oxidative stress in the hippocampus of melamine-exposed rats. Pharmacol Biochem Behav, 132, 152-159.
- Asadi M, Taghizadeh S, Kaviani E, et al (2022): Caspase-3: Structure, function, and biotechnological aspects. Biotechnol Appl Bioc, 69:1633–1645.
- Buur JL, Baynes RE, Riviere JE (2008): Estimating meat withdrawal times in pigs exposed to melamine contaminated feed using a physiologically based pharmacokinetic model. Regul Toxicol Pharmacol, 51, 324-331.
- Chang L, Wu Q, She R, et al (2021): The pathologic lesions of liver caused by melamine alone or in combination with cyanuric acid in mice. Res Vet Sci, 136, 230-238.
- Chen HC, Feng WW, Audira G, et al (2024): Evaluation of sub-chronic toxicity of melamine via systematic or oral delivery in adult zebrafish based on behavioral endpoints. NeuroToxicology, 102, 68-80.
- Choi BE, Shin S, Evans S, et al (2023): Ablation of TRPC3 disrupts Ca2+ signaling in salivary ductal cells and promotes sialolithiasis. Sci Rep., 13, 5772.
- Cory S, Adams JM (2002): The Bcl-2 family: Regulators of the cellular life-or-death switch. Nat Rev Cancer, 2, 647-656.
- Dalal R, Goldfarb D (2011): Melamine-related kidney stones and renal toxicity. Nat Rev Nephrol., 7, 267–274.
- Delbridge ARD, Strasser A (2015): The BCL-2 protein family, BH3-mimetics, and cancer therapy. Cell Death Differ, 22, 1071-1080.
- Devrim AK, Sozmen M, Devrim T, et al (2017): Periostin normalizes levels of cardiac markers in rats with experimental isoproterenol cardiotoxicity. Bratisl Med J, 118, 705–709.
- Devrim T, Ekici H, Devrim AK, et al (2020): Late effects of cutaneous 3-methylcholanthrene exposure on DNA damage-related pleiotropic growth factors and oxidative stress markers in mice. Bratisl Lek Listy, 121, 325-330.
- Dharnidharka VR (2009): Melamine-contaminated powdered formula and urolithiasis. N Engl J Med, 360, 2676-8.
- Erisgin Z, Mutlu HS, Tekelioglu Y, et al (2021): Hepatotoxic effects of melamine exposure from the weaning period in rats: a flow cytometric, electron microscopic, and histopathologic study. Toxicol Res, 10, 418-424.
- Ganji L, Alebouyeh M, Shirazi MH, et al (2019): Comparative transcriptional analysis for Toll-like receptors, inflammatory cytokines, and apoptotic genes in response to different cytolethal-encoding and noncoding isolates of Salmonella enterica and Campylobacter jejuni from food and human stool. Microb Pathog, 133, 103550.
- Gupta PK (2020): In: Problem Solving Questions in Toxicology: Target Organ Toxicity. Springer, Cham, 83, 117.
- Habotta OA, Abdeen A, Roomi AB, et al (2023): Nootkatone Mitigated Melamine-Evoked Hepatotoxicity by Featuring Oxidative Stress and Inflammation Interconnected Mechanisms: In Vivo and In Silico Approaches. Toxics, 11, 784.
- Huang J, Yang G, Xia F, et al (2018): Reproductive toxicity of melamine against male mice and the related mechanism. Toxicol Mech Methods, 28, 345-352.
- Kintz H, Nylen E, Barber A (2020): Inclusion of Dap10 or 4-1BB costimulation domains in the chPD1 receptor enhances anti-tumor efficacy of T cells in murine models of lymphoma and melanoma. Cell Immunol, 351, 104069.
- Le Na NT, Duc Loc S, Minh Tri NL, et al (2019): Nanomelanin potentially protects the spleen from radiotherapy-associated damage and enhances immunoactivity in tumor-bearing mice. Materials, 12, 1725.
- Mbazima VG, Mokgotho MP, February F, et al (2018): Cellular and molecular mechanism associated with anticancer activity of Commelina benghalensis. Int J Histol Cytol, 5, 415-422.
- Menzie-Suderam JM, Mohammad-Gharibani P, Modi J, et al (2018): Granulocyte-colony stimulating factor protects against endoplasmic reticulum stress in an experimental model of stroke. Brain Res, 1682, 1-13.
- Ramalho RM, Cortez-Pinto H, Castro RE, et al (2006): Apoptosis and Bcl-2 expression in the livers of patients with steatohepatitis. Eur J Gastroenterol Hepatol, 18, 21-29.
- Sak S, Uyanikoglu H, Incebiyik A, et al (2018): Associations of serum fetuin-A and oxidative stress parameters with polycystic ovary syndrome. Clin Exp Reprod Med, 45, 116–121.
- Sharma S, Varsha KK, Kumari S, et al (2020): Acute toxicity analysis of Disarib, an inhibitor of BCL2. Scientific Rep, 10, 15188.
- Shojaie L, Bogdanov JM, Alavifard H, et al (2024): Innate and adaptive immune cell interaction drives inflammasome activation and hepatocyte apoptosis in murine liver injury from immune checkpoint inhibitors. Cell Death Dis, 15, 140.
- Siddiqui WA, Ahad A, Ahsan H (2015): The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update. Arch Toxicol, 89, 289-317.
- Sonobe A, Jesmi, S, Shimojo N, et al (2015): Concomitant down-regulation of Et1-Etb system and VEGF angiogenic signaling in the frontal cortex of endotoxemic mice: A heightened vulnerability to cerebral microcirculation in sepsis. J Vasc Med Surg, 3, 2-7.
- Tessoulin B, Papin A, Gomez-Bougie P, et al (2019): BCL2-family dysregulation in B-cell malignancies: from gene expression regulation to a targeted therapy biomarker. Front Oncol, 8, 645.
- Tsujimoto Y (2002): Bcl-2 family of proteins: life-or-death switch in mitochondria. Biosci Rep, 22, 47-58.
- Wan S, Wang X, Chen W, et al (2024): Exposure to high dose of polystyrene nanoplastics causes trophoblast cell apoptosis and induces miscarriage. Part Fibre Toxicol, 21,13.
- Victorino F, Bigley T, Park E, et al (2021): HIF1α is required for NK cell metabolic adaptation during virus infection. Elife, 10, e68484.
- Yin RH, Wang XZ, Bai WL, et al (2013): The reproductive toxicity of melamine in the absence and presence of cyanuric acid in male mice. Res Vet Sci, 94, 618-627.
- Zhao M, Zhang NX, Economou M, et al (1994): Immunohistochemical detection of bcl-2 protein in liver lesions: bcl-2 protein is expressed in hepatocellular carcinomas but not in liver cell dysplasia. Histopathology, 25, 237-245.
There are 36 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Veterinary Sciences (Other) |
| Journal Section | Research Article |
| Authors | |
| Project Number | Project number 2019/053. |
| Early Pub Date | December 4, 2024 |
| Publication Date | April 1, 2025 |
| Submission Date | September 14, 2024 |
| Acceptance Date | November 27, 2024 |
| Published in Issue | Year 2025Volume: 72 Issue: 2 |
