Preview

Experimental and Clinical Gastroenterology

Advanced search

Prevention of aluminum-induced hepatotoxicity by a complex of oxidized pectin and oxymethyluracil: an experimental study in rats

https://doi.org/10.31146/1682-8658-ecg-240-8-175-194

Abstract

Objective - The aim of the study was to experimentally assess the preventive effect of a complex of oxidized pectin and oxymethyluracil on chronic aluminum-induced hepatotoxicity in rats based on molecular and biochemical parameters. Materials and Methods. The experiment was conducted on 56 outbred female rats that received oral administration of aluminum hydroxide at a dose of 15 mg/kg and a chelate complex of oxidized pectin with oxymethyluracil (50 mg/kg) under various preventive and post-exposure regimens for 3-4 months. The expression of metallothionein genes (Mt1, Mt2, Mt3) and zinc transporter genes (Zip1, Zip8) in liver tissue was determined by real-time PCR using specific primers, SYBR Green intercalating dye, and the reference gene Gapdh. Serum activity of AST, ALT, ALP, and LDH was measured; statistical analysis was performed using IBM SPSS Statistics 21 software with one-way ANOVA at a critical significance level of p=0,05. Results. In our study, chronic aluminum exposure was associated with an increase in Zip1 gene expression in the liver, whereas continuous administration of the oxidized pectin-oxymethyluracil complex normalized its expression to control levels. The expression of Zip8 and metallothionein genes (Mt1a, Mt2a, Mt3a) did not change significantly among the experimental groups. At the biochemical level, this complex, when used preventively, contributed to a reduction in AST and LDH activity. Conclusion. The oxidized pectin-oxymethyluracil complex in a rat model of chronic aluminum hydroxide exposure normalizes Zip1 gene expression and reduces AST and LDH activity. Further studies using an expanded set of morphological and molecular markers are required to clarify the organoprotective mechanisms of the complex.

About the Authors

T. G. Yakupova
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation


A. A. Gizatullina
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation


D. D. Karimov
Ufa Research Institute of Occupational Health and Human Ecology; Ufa University of Science and Technology
Russian Federation


G. F. Muhammadieva
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation


N. Yu. Khusnutdinova
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation


D. A. Smolyankin
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation


Yu. S. Zimin
Ufa University of Science and Technology
Russian Federation


G. G. Kutlugildina
Ufa University of Science and Technology
Russian Federation


D. O. Karimov
Ufa Research Institute of Occupational Health and Human Ecology; N.A. Semashko National Research Institute of Public Health
Russian Federation


References

1. Alasfar R. H., Isaifan R. J. Aluminum environmental pollution: the silent killer. Environmental Science and Pollution Research International. 2021 Sep;28(33):44587-44597. doi: 10.1007/s11356-021-14700-0ю

2. Igbokwe I. O., Igwenagu E., Igbokwe N. A. Aluminium toxicosis: a review of toxic actions and effects.Interdisciplinary Toxicology. 2019 Oct;12(2):45-70.

3. Sabir D. K., Al-Masri A., Aldayel M. F., Sharaf A. A. Modulating oxidative stress, apoptosis, and mitochondrial dysfunctions on cardiotoxicity induced by aluminum phosphide pesticide using resveratrol. Toxicological Mechanisms and Methods. 2024 Jul;34(6):727-735.

4. Ganhör C., Mayr L., Zolles J. et al. Airborne Aluminum as an Underestimated Source of Human Exposure: Quantification of Aluminum in 24 Human Tissue Types Reveals High Aluminum Concentrations in Lung and Hilar Lymph Node Tissues. Environmental Science & Technology. 2024 Jul 02;58(26):11292-11300.

5. Berlana D., López-Hellín J., Pau-Parra A., Ferrer-Costa R.Comparing Aluminum Concentrations in Adult and Pediatric Parenteral Nutrition Solutions: Multichamber-Bag versus Compounded Parenteral Nutrition. Nutrients. 2024 Apr 01;16(7).

6. de Lima W. F., Né Y. G.S., Aragão W. A.B. et al. Global Scientific Research Landscape on Aluminum Toxicology. Biological Trace Element Research. 2023 Jul;201(7):3210-3224.

7. Exley C. A biogeochemical cycle for aluminium? Journal of Inorganic Biochemistry. 2003 Sep 15;97(1):1-7.

8. Mudge D. W., Johnson D. W., Hawley C. M., et al. Do aluminium-based phosphate binders continue to have a role in contemporary nephrology practice? BMC Nephrology. 2011 May 13;12:20.

9. Rahimzadeh M. R., Kazemi S., Amiri R. J., et al. Aluminum Poisoning with Emphasis on Its Mechanism and Treatment of Intoxication. Emergency Medicine International. 2022;2022:1480553.

10. Livak K. J., Schmittgen T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-408. doi: 10.1006/meth.2001.1262.

11. Kutlugildina G. G., Zimin Yu.S., Mustafin A. G., Sakhibgareeva M. V., Spivak S. I. The kinetic scheme of oxidative transformations of apple pekpodtin is represented by an ozone-oxygen mixture // Butlerov communications. 2020;61(2):79-89. (in Russ.)@@ Кутлугильдина Г. Г., Зимин Ю. С., Мустафин А. Г., Сахибгареева М. В., Спивак С. И. Кинетическая схема окислительных превращений яблочного пекподтина представлена озоно-кислородной смесью. Бутлеровские сообщения. 2020;61(2):79-89.

12. Kutlugildina G. G., Zimin Yu.S., Gimadieva A. R., Karimov D. O., Khusnutdinova N.Yu., Repina E. F. [Complex compound of 5-aminosalicylic acid with oxidized pectin exhibiting antiulcer activity, and a method for its production].Russian Federation Patent for Invention RU 2 818 489 C1. - 2024. (in Russ.)@@ Кутлугильдина Г. Г., Зимин Ю. С., Гимадиева А. Р., Каримов Д. О., Хуснутдинова Н. Ю., Репина Э. Ф. Комплексное соединение 5-аминосалициловой кислоты с окисленным пектином, проявляющее противоязвенную активность, и способ его получения. Патент РФ на изобретение RU 2 818 489 C1. -2024.

13. Ghorbel I., Chaabane M., Elwej A. et al. Expression of metallothioneins I and II related to oxidative stress in the liver of aluminium-treated rats. Archives of Physiology and Biochemistry. 2016 Oct;122(4):214-222. doi: 10.1080/13813455.2016.1187176.

14. Wang X., Li M., Liu Y. et al. Oxidized pectin/collagen self-healing hydrogel accelerated wound healing and skin regeneration.International Journal of Biological Macromolecules. 2025;237:124618.

15. Khosrowshahi N. D., Amini H., Khoshfetrat A. B., Rahbarghazi R. Oxidized pectin/collagen self-healing hydrogel accelerated the regeneration of acute hepatic injury in a mouse model.International Journal of Biological Macromolecules. 2025 Apr;304(Pt 2):140931. doi: 10.1016/j.ijbiomac.2025.140931.

16. Myshkin V. A., Enikeyev D. A., Srubilin D. V. Antitoxic protection of the body using antidotes, antioxidants and other membrane protectors. Archiv EuroMedica. 2014;4(2):51-56.


Review

For citations:


Yakupova T.G., Gizatullina A.A., Karimov D.D., Muhammadieva G.F., Khusnutdinova N.Yu., Smolyankin D.A., Zimin Yu.S., Kutlugildina G.G., Karimov D.O. Prevention of aluminum-induced hepatotoxicity by a complex of oxidized pectin and oxymethyluracil: an experimental study in rats. Experimental and Clinical Gastroenterology. 2025;(8):175-194. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-240-8-175-194

Views: 15

JATS XML


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-8658 (Print)