Skip to main content
Log in

The deleterious effects of cadmium on oxidative stress markers, drug-metabolizing, and antioxidant enzyme activities: Role of Silymarin and Garlic as Antioxidants

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Exposure to cadmium has been related to liver and kidney diseases such as polycystic and nephrotic syndrome. It is still unclear how cadmium contributes to these diseases. It is believed that the induction of oxidative stress resulting from the inhibition of antioxidant enzyme activities and changes in drug-metabolizing enzymes in the liver could explain the role of cadmium in the development of different diseases in the kidney and probably other organs. Changes in oxidative stress markers, antioxidant enzymes, and drug-metabolizing enzyme activities were assessed in the liver of male rats exposed to cadmium chloride. Additionally, the protective effects of silymarin and garlic extract against cadmium toxicosis were evaluated. Rats were randomly divided into eight groups as follows, groups 1, 2, 3, 4, and 5, received orally saline, CdCl2 (1 mg/kg), garlic extract [800 mg/kg], silymarin (25 mg/kg) and silymarin plus garlic extract respectively for 28 consecutive days. Rats in groups 6, 7, and 8 were pretreated with the same doses of garlic, silymarin, and garlic plus silymarin, respectively for two hours before cadmium administration. The Western immunoblotting technique was used to investigate the protein expression of cytochrome P450 isozymes. Spectrophotometric methods were used to assess the activity of both antioxidant- and drug-metabolizing enzymes. Free radical levels [measured as thiobarbituric acid reactive substances (TBARS)], catalase, superoxide dismutase, and glutathione peroxidase activities increased whereas the levels of glutathione and the activities of glutathione S-transferase, glutathione reductase, and glutamyl transferase, cytochrome P450, aryl hydrocarbon dehydrogenase (AHH), dimethylnitrosamine-N-demethylase I (DMN-dI), 7-ethoxycoumarine-O-deethylase (ECOD), cytochrome b5 and NADPH-Cytochrome-c-reductase enzyme activities decreased after cadmium treatment. Furthermore, Western immunoblotting data revealed that glutathione peroxidase protein expression increased following cadmium exposure, but cytochrome P450 2E1 and 3A4 expressions were downregulated. However, pretreatment of rats with silymarin or garlic extract or both before cadmium administration was found to restore the protein expression of cytochrome P450 2E1 and 3A4, the level of free radicals, antioxidant enzymes, drug-metabolizing enzyme activities to their normal levels. Similarly, histological studies revealed that silymarin and/or garlic extract reduced the liver damage caused by cadmium. Silymarin and/or garlic extract reduced the adverse effects of cadmium on the activity of both drug-metabolizing and antioxidant enzymes activity. These antioxidants could be provided to those who work in cadmium-based sectors to help them cope with the adverse effects of cadmium on their kidneys. In addition, Inhibiting drug-metabolizing enzyme activity should be considered when administering therapeutic medications to persons exposed to cadmium because most therapeutic drugs and many endogenous substances are largely metabolized by these enzymes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

Not applicable.

Abbreviations

AHH:

Aryl hydrocarbon dehydrogenase

DMN-dI:

Dimethylnitrosamine-N-demethylase I

ECOD:

7-Ethoxycoumarine-O-deethylase

GSH:

Cytochrome b5, and NADPH-Cytochrome -c-reductase, glutathione

GR:

Glutathione reductase

GPx:

Glutathione peroxidase

DAS:

Diallyl sulfide

DMN:

Dimethylnitrosamine

B(a)P:

Benzo(a)pyrene

GST:

Glutathione S-transferases

SOD:

Superoxide dismutase

CAT:

Catalase

γ-GT:

γ-Glutamyl transferase

References

Download references

Funding

The authors confirm that the submitted work was not funded by any organization.

Author information

Authors and Affiliations

Authors

Contributions

Salah A. Sheweita was in charge of the research concept and writing the draft and the final versions of the manuscript.

Ahmed Abd El Rafea carried out the experimental work.

Sabah G. Elbana shared in the statistical analysis and writing the draft of the manuscript.

Corresponding author

Correspondence to Salah A. Sheweita.

Ethics declarations

Ethical approval

The local committee of animal care at Graduate Studies and Research, Alexandria University, Egypt, approved the experimental design and methodology, which adhere to the standards of the National Institute of Health, USA.

Consent to participate

Not applicable.

Consent to publish

All authors agree to publish the current study in Environmental Science & Pollution Research.

Conflict of interest

The authors certify that there are no known conflicts of interest that could influence the findings of this study.

Additional information

Responsible Editor: Mohamed M. Abdel-Daim

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sheweita, S.A., Rafea, A.A.E. & Elbana, S.G. The deleterious effects of cadmium on oxidative stress markers, drug-metabolizing, and antioxidant enzyme activities: Role of Silymarin and Garlic as Antioxidants. Environ Sci Pollut Res 30, 112490–112502 (2023). https://doi.org/10.1007/s11356-023-30197-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-023-30197-1

Keywords

Navigation