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Protective effects of cardamom aqueous extract against tamoxifen-induced pancreatic injury in female rats

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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.

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Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

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Acknowledgements

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

Funding

The authors extend their appreciation to the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia for funding this research work through the project no. (IFKSUOR3-154–1).

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P. O. Box: 2454, Riyadh, 11495, Saudi Arabia

    Hala Attia, Alaa Alanteet & Rehab Ali

  2. College of Pharmacy, King Saud University, Riyadh, 11495, Saudi Arabia

    Afraa Alzoubi & Nour Al-anazi

  3. Department of Physiology, College of Medicine, King Saud University, Riyadh, 11495, Saudi Arabia

    Aliah Alshanwani

  4. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt

    Naglaa El-Orabi

  5. Department of Anatomy, College of Medicine, King Saud University, Riyadh, 11495, Saudi Arabia

    Raeesa Mohamad

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  1. Hala Attia
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Contributions

HA, AA, and NA-a contributed to the study conception and design. All authors contributed to methodology, investigations and data analysis. HA wrote the manuscript. Resources were supplied by HA, AA and RM. All authors read and approved the final manuscript.

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Correspondence to Hala Attia.

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Supplementary Information

Below is the link to the electronic supplementary material.

43188_2023_198_MOESM1_ESM.jpg

Supplementary file1 Supplementary file 1: Morphology of the pancreas from the rats in the normal control and tamoxifen (TAM)-intoxicated groups, and from rats treated with 4, 6, 8, 10, and 12 mL/kg of the cardamom aqueous extract (CAE). A: Normal control; B: TAM-intoxicated rats; C: TAM+ CAE (4 mL/kg); D: TAM+ CAE (6 mL/kg); E: TAM+ CAE (8 mL/kg); F: TAM+ CAE (10 mL/kg); G: TAM+ CAE (12 mL/kg) (JPG 36 KB)

Supplementary file2 (DOC 102 KB)

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Supplementary file3 Photomicrographs of the rat pancreas stained with hematoxylin and eosin. Scale bar; 100μm. Effect of different doses of the cardamom aqueous extract (CAE) on the histological changes following tamoxifen (TAM) intoxication (A) Section of the pancreas from control rat showing normal histological features of pancreatic acini (long arrows), normal multiple islets of Langerhans (stars) and normal thin slit-like septa (short arrows). (B) Pancreatic section from rat that received TAM showing marked depletion of pancreatic acini (long arrows). The acini were atrophic with degeneration of their lining epithelium, and there were no prominent islets of Langerhans. A marked increase in the thickness of the connective tissue septa (short arrows) infiltrated with many inflammatory cells was observed. (C) & (D) Sections of the pancreas from rats that concomitantly received 4 or 6 mL/kg CAE, respectively, showing histopathological changes mimicking the TAM-intoxicated group. (E) Pancreatic section from rat that received 8 mL/kg CAE +TAM showing the appearance of many acini and decreased connective tissue septa (short arrows) compared with that in the 4 and 6 mL/kg groups. (F) & (G) Sections of the pancreas from rats that received 10 and 12 mL/kg CAE + TAM showing an increase in the number of islets of Langerhans (stars) and acini (long arrows), with a marked decrease in connective tissue septa (short arrows) particularly at 10 mL/kg. (JPG 200 KB)

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Supplementary file4 Supplementary file 4. Effect of the different doses of the cardamom aqueous extract (CAE) on the levels of serum α-amylase, pancreatic lipase, triglycerides (TG) and glucose in tamoxifen (TAM)-intoxicated female rats. a: significant difference vs normal control, b: Significant difference vs. TAM-intoxicated group, c and d: Significant differences vs. 10 and 12 ml/kg-treated groups, respectively. ***p < 0.001, ** p < 0.01, * p < 05. (JPG 128 KB)

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Attia, H., Alzoubi, A., Al-anazi, N. et al. Protective effects of cardamom aqueous extract against tamoxifen-induced pancreatic injury in female rats. Toxicol Res. 39, 721–737 (2023). https://doi.org/10.1007/s43188-023-00198-w

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