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Volume 14
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10.3390/cells14231906
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Thymoquinone Attenuates Aluminum Chloride-Induced Testicular Injury by Inhibiting NLRP3/Caspase 1/IL-1β Inflammasome Signaling and Polarizing the Macrophages Toward Anti-Inflammatory M2 Phenotype

by
Heba M. Elhessy
1,2,
Basma Adel Khattab
1,
Alaa M. Badawy
1,
Hassan Reda Hassan Elsayed
1,3,*,
Mansour A. Alghamdi
3,4,
Hind Zafrah
5,
Mohammed R. Rabei
6,7,
Ola A. Habotta
8,9 and
Nermeen H. Lashine
1
1
Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
2
Department of Anatomy and Embryology, Faculty of Medicine, New Mansoura University, Mansoura 35516, Egypt
3
Department of Anatomy, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia
4
Genomics and Personalized Medicine Unit, The Center for Medical and Health Research, King Khalid University, Abha 62529, Saudi Arabia
5
Department of Physiology, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia
6
Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51432, Saudi Arabia
7
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
8
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
9
Horus Research Center, Horus University, New Damietta 34518, Egypt
*
Author to whom correspondence should be addressed.
Cells 2025, 14(23), 1906; https://doi.org/10.3390/cells14231906 (registering DOI)
Submission received: 6 November 2025 / Revised: 25 November 2025 / Accepted: 28 November 2025 / Published: 1 December 2025
(This article belongs to the Section Tissues and Organs)
Versions Notes

Abstract

In recent decades, the quantity of sperm and the quality of semen have decreased, causing an increased incidence of male infertility. The increased exposure to environmental pollutants and metals, including aluminum, is one of the causes. Aluminum is reported to activate the proinflammatory macrophages and the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome pathway in many organs. Thymoquinone (TQ), the bioactive component of Nigella sativa, possesses immunomodulatory, anti-inflammatory, anti-apoptotic, and antioxidant properties. The purpose of this work is to investigate how thymoquinone affects aluminum chloride (AlCl3)-induced testicular damage and to study, for the first time, its role in modifying the inflammasome pathway, specifically NLRP3/caspase-1/IL-1β, and in targeting macrophage polarization. Negative control, TQ control (10 mg/kg/d), AlCl3 group (100 mg/kg/d), and AlCl3 + TQ group were the rat groups. Serum testosterone, FSH, and LH were measured, along with a seminal analysis, evaluation of testicular oxidative stress markers, and assessment of testicular enzymes LDH, SDH, and ACP. NLRP3, caspase-1, IL-1β, CD68, and CD163 immunohistochemical staining, as well as histological alterations, were evaluated. TQ could lower oxidative stress markers, limit the AlCl3-induced activation of the NLRP3/caspase-1/IL-1β inflammasome pathway, and induce macrophage polarization toward an M2 anti-inflammatory phenotype, thereby restoring testicular enzymes, histological structure, semen quality, and hormone levels. Thymoquinone attenuates aluminum chloride-induced testicular injury by inhibiting NLRP3/caspase-1/IL-1β inflammasome signaling and polarizing the macrophages toward an anti-inflammatory M2 phenotype.
Keywords: aluminum; testicular injury; inflammasome; NLRP3; caspase-1; IL-1β; macrophage polarization aluminum; testicular injury; inflammasome; NLRP3; caspase-1; IL-1β; macrophage polarization

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MDPI and ACS Style

Elhessy, H.M.; Khattab, B.A.; Badawy, A.M.; Elsayed, H.R.H.; Alghamdi, M.A.; Zafrah, H.; Rabei, M.R.; Habotta, O.A.; Lashine, N.H. Thymoquinone Attenuates Aluminum Chloride-Induced Testicular Injury by Inhibiting NLRP3/Caspase 1/IL-1β Inflammasome Signaling and Polarizing the Macrophages Toward Anti-Inflammatory M2 Phenotype. Cells 2025, 14, 1906. https://doi.org/10.3390/cells14231906

AMA Style

Elhessy HM, Khattab BA, Badawy AM, Elsayed HRH, Alghamdi MA, Zafrah H, Rabei MR, Habotta OA, Lashine NH. Thymoquinone Attenuates Aluminum Chloride-Induced Testicular Injury by Inhibiting NLRP3/Caspase 1/IL-1β Inflammasome Signaling and Polarizing the Macrophages Toward Anti-Inflammatory M2 Phenotype. Cells. 2025; 14(23):1906. https://doi.org/10.3390/cells14231906

Chicago/Turabian Style

Elhessy, Heba M., Basma Adel Khattab, Alaa M. Badawy, Hassan Reda Hassan Elsayed, Mansour A. Alghamdi, Hind Zafrah, Mohammed R. Rabei, Ola A. Habotta, and Nermeen H. Lashine. 2025. "Thymoquinone Attenuates Aluminum Chloride-Induced Testicular Injury by Inhibiting NLRP3/Caspase 1/IL-1β Inflammasome Signaling and Polarizing the Macrophages Toward Anti-Inflammatory M2 Phenotype" Cells 14, no. 23: 1906. https://doi.org/10.3390/cells14231906

APA Style

Elhessy, H. M., Khattab, B. A., Badawy, A. M., Elsayed, H. R. H., Alghamdi, M. A., Zafrah, H., Rabei, M. R., Habotta, O. A., & Lashine, N. H. (2025). Thymoquinone Attenuates Aluminum Chloride-Induced Testicular Injury by Inhibiting NLRP3/Caspase 1/IL-1β Inflammasome Signaling and Polarizing the Macrophages Toward Anti-Inflammatory M2 Phenotype. Cells, 14(23), 1906. https://doi.org/10.3390/cells14231906

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