Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Protective effects of cardamom aqueous extract against tamoxifen-induced pancreatic injury in female rats

  • Hala Attia (Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University) ;
  • Afraa Alzoubi (College of Pharmacy, King Saud University) ;
  • Nour Al‑anazi (College of Pharmacy, King Saud University) ;
  • Aliah Alshanwani (Department of Physiology, College of Medicine, King Saud University) ;
  • Naglaa El‑Orabi (Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University) ;
  • Alaa Alanteet (Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University) ;
  • Raeesa Mohamad (Department of Anatomy, College of Medicine, King Saud University) ;
  • Rehab Ali (Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University)
  • Received : 2022.12.09
  • Accepted : 2023.06.07
  • Published : 2023.10.15
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Abstract

Tamoxifen (TAM) is a commonly used drug for breast cancer treatment. Although effective, TAM has deleterious effects on many organs. The toxic effects of TAM on the pancreas and the underlying mechanisms however, have not fully investigated. In the present study, we investigated the effects of TAM on the pancreatic tissue in female rats. We also examined whether cardamom aqueous extract (CAE) protects against TAM-induced pancreatic injury. TAM-intoxicated rats were injected with 45 mg/kg of TAM for 10 days, whereas rats in the CAE-treated group were administered 10 mL/kg of CAE for 20 days, starting 10 days prior to TAM administration. Treatment with TAM resulted in severe degeneration of the pancreatic acini and marked increases in the serum levels of pancreatic lipase, α-amylase, glucose, fatty acids and triglycerides along with decreased insulin serum levels. TAM led to oxidative stress as evident from a significant increase in the pancreatic levels of lipid peroxides and nitric oxide along with the depletion of reduced glutathione, glutathione peroxidase, and superoxide dismutase. Moreover, inflammation was indicated by a significant increase in tumor necrosis factor-α and interleukin-6 levels, enhanced expression of the macrophage recruitment marker; CD68 as well as up-regulated protein levels of toll-like receptor 4 and nuclear factor kappa B and increased p-p38/MAPK ratio; which are important signals in the production of inflammatory cytokines. TAM also markedly increased the pancreatic levels of caspase-3 and BAX reflecting its apoptotic effects. The CAE treatment ameliorated all the biochemical and histological changes induced by TAM. The present study revealed, for the first time, that TAM has toxic effects on the pancreatic tissue through oxidative stress, inflammation and apoptotic effects. The present study also provides evidence that CAE exerts cytoprotective effects against these deleterious effects induced by TAM in the pancreatic tissue.

Keywords

Acknowledgement

Authors extend their appreciation to Prince Naif Health Research Center, Investigator support Unit for the language editing service provided.

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