PLGA-Encapsulated Pterostilbene Mitigates Cadmium-Induced Nephrotoxicity in Rats by Modulating Oxidative Stress, Inflammation, and Apoptosis.
6 affiliations
- 1Department of Medical Laboratory Technology, College of Nursing and Health Science, Jazan University, Jazan 45142, Saudi Arabia.
- 2Center for Health Research, Northern Border University, Arar 73213, Saudi Arabia.
- 3Department of Biology, College of Science, Jouf University, Sakaka 72341, Saudi Arabia.
- 4Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
- 5Horus Research Center, Horus University-Egypt (HUE), New Damietta 34518, Egypt.
- 6Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
Abstract
Cadmium (Cd) is an environmentally pervasive toxic metal that accumulates in the kidney and promotes oxidative stress, inflammation, and apoptosis. This study evaluated the renoprotective effects of free pterostilbene (PTS) and PLGA-encapsulated PTS (PTS-PLGA) in male Sprague-Dawley rats with Cd-induced nephrotoxicity. Rats received CdCl₂ (2 mg/kg/day, intraperitoneally) for 3 weeks and oral free PTS or PTS-PLGA at a nominal PTS-equivalent dose of 50 mg/kg/day. The formulation dose was calculated from encapsulation efficiency; however, systemic and renal PTS exposure were not measured. Renal function, kidney injury molecule-1 (Kim-1), oxidative stress, inflammatory, and apoptosis-related markers were assessed together with histopathological, ultrastructural, and immunohistochemical changes. Cd exposure impaired renal function and increased Kim-1, reactive oxygen species, malondialdehyde, protein carbonyls, 8-hydroxy-2'-deoxyguanosine, inflammatory mediators, caspase activities, Bax/Bcl-2 ratio, and p53 expression. These changes were accompanied by reduced antioxidant defenses and Nrf2/HO-1-related markers, as well as marked histological and ultrastructural injury. Both PTS formulations attenuated Cd-associated renal alterations. Under the present dosing conditions, PTS-PLGA was associated with greater improvement than free PTS across most endpoints. PLGA-encapsulated PTS therefore warrants further preclinical investigation as a potential approach to mitigate Cd-induced nephrotoxicity; pharmacokinetic, biodistribution, and empty-carrier control studies are needed to define the basis of the observed formulation-related differences.
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BibTeX
@article{alaajam2026plgaencapsulated,
title = {{PLGA-Encapsulated Pterostilbene Mitigates Cadmium-Induced Nephrotoxicity in Rats by Modulating Oxidative Stress, Inflammation, and Apoptosis.}},
author = {Fahd Alaajam and Ekramy M Elmorsy and Amro Duhduh and Abdulrahman S Aldaghmi and Fahad Alshammari and Ola A Habotta and Manal S Fawzy and Shaimaa A Shehata},
journal = {Toxics},
year = {2026},
month = sep,
doi = {10.3390/toxics14100856},
url = {https://europepmc.org/article/MED/42931643},
note = {CC BY},
}
RIS
TY - JOUR
TI - PLGA-Encapsulated Pterostilbene Mitigates Cadmium-Induced Nephrotoxicity in Rats by Modulating Oxidative Stress, Inflammation, and Apoptosis.
AU - Fahd Alaajam
AU - Ekramy M Elmorsy
AU - Amro Duhduh
AU - Abdulrahman S Aldaghmi
AU - Fahad Alshammari
AU - Ola A Habotta
AU - Manal S Fawzy
AU - Shaimaa A Shehata
PY - 2026
DA - 2026/09/26
JO - Toxics
DO - 10.3390/toxics14100856
UR - https://europepmc.org/article/MED/42931643
AB - Cadmium (Cd) is an environmentally pervasive toxic metal that accumulates in the kidney and promotes oxidative stress, inflammation, and apoptosis. This study evaluated the renoprotective effects of free pterostilbene (PTS) and PLGA-encapsulated PTS (PTS-PLGA) in male Sprague-Dawley rats with Cd-induced nephrotoxicity. Rats received CdCl₂ (2 mg/kg/day, intraperitoneally) for 3 weeks and oral free PTS or PTS-PLGA at a nominal PTS-equivalent dose of 50 mg/kg/day. The formulation dose was calculated from encapsulation efficiency; however, systemic and renal PTS exposure were not measured. Renal function, kidney injury molecule-1 (Kim-1), oxidative stress, inflammatory, and apoptosis-related markers were assessed together with histopathological, ultrastructural, and immunohistochemical changes. Cd exposure impaired renal function and increased Kim-1, reactive oxygen species, malondialdehyde, protein carbonyls, 8-hydroxy-2'-deoxyguanosine, inflammatory mediators, caspase activities, Bax/Bcl-2 ratio, and p53 expression. These changes were accompanied by reduced antioxidant defenses and Nrf2/HO-1-related markers, as well as marked histological and ultrastructural injury. Both PTS formulations attenuated Cd-associated renal alterations. Under the present dosing conditions, PTS-PLGA was associated with greater improvement than free PTS across most endpoints. PLGA-encapsulated PTS therefore warrants further preclinical investigation as a potential approach to mitigate Cd-induced nephrotoxicity; pharmacokinetic, biodistribution, and empty-carrier control studies are needed to define the basis of the observed formulation-related differences.
SN - 2305-6304
ER -