Differential Protective Effect of Zinc and Magnesium for the Hepatic and Renal Toxicity Induced by Acetaminophen and Potentiated with Ciprofloxacin in Rats

Medicina (Kaunas). 2024 Apr 8;60(4):611. doi: 10.3390/medicina60040611.

Abstract

Background and Objectives: The purpose of this study was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally induced with acetaminophen (AAPh) and potentiated by a ciprofloxacin addition in rats. Material and Methods: The experiment was performed on five animal groups: group 1-control, treated for 6 weeks with normal saline, 1 mL/kg; group 2-AAPh, treated for 6 weeks with AAPh, 100 mg/kg/day; group 3-AAPh + C, treated for 6 weeks with AAPh 100 mg/kg/day and ciprofloxacin 50 mg/kg/day, only in the last 14 days of the experiment; group 4-AAPh + C + Mg, with the same treatment as group 3, but in the last 14 days, MgCl2 10 mg/ kg/day was added; and group 5-AAPh + C + Zn, with the same treatment as group 3, but in the last 14 days, zinc gluconate (ZnG), 10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (p < 0.001 group 2 vs. group 1 for all mentioned parameters). Furthermore, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, at 0.001 < p < 0.01 and 0.01 < p < 0.05, respectively). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days, resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine (0.01 < p < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against the increase in liver enzymes, and a more pronounced protection against the increase in serum urea and creatinine (0.001 < p < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < p < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in the case of ZnG, to a higher extent, especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < p < 0.05 group 5 vs. group 4). Conclusions: This study presents further proof for the beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney's function, and the antioxidant profile improvement has a key role, especially in the case of zinc gluconate.

Keywords: acetaminophen; ciprofloxacin; hepatoprotection; magnesium; zinc.

MeSH terms

  • Acetaminophen*
  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Ciprofloxacin* / pharmacology
  • Ciprofloxacin* / therapeutic use
  • Drug Synergism
  • Gluconates* / pharmacology
  • Gluconates* / therapeutic use
  • Kidney / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Magnesium / pharmacology
  • Magnesium / therapeutic use
  • Magnesium Chloride / pharmacology
  • Magnesium Chloride / therapeutic use
  • Male
  • Rats
  • Rats, Wistar*
  • Zinc / pharmacology
  • Zinc / therapeutic use

Substances

  • Ciprofloxacin
  • Acetaminophen
  • Gluconates
  • gluconic acid
  • Zinc
  • Magnesium
  • Magnesium Chloride
  • Alanine Transaminase
  • Aspartate Aminotransferases

Grants and funding

Funding Research has been financed by the researchers’ own resources. Availability of data and materials: The content of this manuscript has not been copyrighted or published previously. The content of this manuscript is not currently under consideration for publication elsewhere. The content of this manuscript will not be copyrighted, submitted, or published elsewhere while it is under consideration for acceptance by “Medicina”. There are no directly related manuscripts or abstracts, published or unpublished, by any authors of this paper. Ethics approval and consent to participate in the study protocols were approved by the institution’s Research Ethics Committee (at the Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania) (6 August 2019). All animal procedures were performed in accordance with European Union legislation (EU Directive 2010/63/EU for animal experiments) and the Romanian Law of Research no. 206/27.05.2004, and in accordance with the Helsinki Declaration recommendations. As this manuscript presents the results of an experimental study on laboratory animals (rats) and not the results of a clinical study, the subject consent requirement does not apply. Consent for publication: All authors of this manuscript have read and approved the final version submitted. The representatives of the Institute (the Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania) are fully aware of this submission.