Volume 6, Issue 2 (Avicenna Journal of Pharmaceutical Research, Dec 2026)
Avicenna J Pharma Res 2026, 6(2): 81-87 |
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Kheradmand Y, Ahmadimoghaddam D, Ghaffari F, Hashemi S A, Omidifar N, Nili-Ahmadabadi A. Polyrhodanine Nanoencapsulation Potentiates N-Acetylcysteine Against Paraquat-Induced Cytotoxicity in HepG2 Cells. , Avicenna J Pharma Res. 2026; 6 (2) :81-87
URL: http://ajpr.umsha.ac.ir/article-1-121-en.html
URL: http://ajpr.umsha.ac.ir/article-1-121-en.html
Yekta Kheradmand1 
, Davoud Ahmadimoghaddam1 , Fatemeh Ghaffari2 , Seyyed Alireza Hashemi3 , Navid Omidifar4 , Amir Nili-Ahmadabadi *5
, Davoud Ahmadimoghaddam1 , Fatemeh Ghaffari2 , Seyyed Alireza Hashemi3 , Navid Omidifar4 , Amir Nili-Ahmadabadi *5
1- 1 Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran & 2 Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
2- 1 Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran & 3 Department of Tissue Engineering and Biomaterials, Hamadan University of Medical Sciences, Hamadan, Iran.
3- 4 Health Policy Research Center, Health Institute, Shiraz University of Medical Sciences, Shiraz, Iran
4- 5 Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
5- 1 Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran & 6 Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
2- 1 Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran & 3 Department of Tissue Engineering and Biomaterials, Hamadan University of Medical Sciences, Hamadan, Iran.
3- 4 Health Policy Research Center, Health Institute, Shiraz University of Medical Sciences, Shiraz, Iran
4- 5 Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
5- 1 Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran & 6 Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Abstract: (7 Views)
Background: Paraquat (PQ) poisoning causes severe oxidative stress–mediated hepatotoxicity. Although N-acetylcysteine (NAC) is a promising therapeutic agent, its low bioavailability remains a challenge for clinical application. This study evaluated whether N-acetylcysteine-loaded polyrhodanine nanoparticles (PR-NAC) enhance cytoprotection against PQ-induced injury in HepG2 cells compared with free NAC.
Methods: Cell viability was assessed using the MTT assay across increasing PQ concentrations, either alone or in combination with NAC or PR-NAC. Following determination of the PQ IC50 and evaluation of its interaction with safe doses NAC and PR-NAC, mitochondrial membrane potential (ΔΨm), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and catalase (CAT) activity were assessed.
Results: PQ exposure (IC50 = 17.47 µg/mL) significantly compromised cell membrane integrity, collapsed the ΔΨm, and SOD and CAT activities. PR-NAC provided greater protection than free NAC, shifting the PQ IC50 to 26.41 µg/mL and restoring ΔΨm to levels close to those of the control group. PR-NAC also increased SOD and CAT activities to a degree comparable to that of NAC.
Conclusion: These findings demonstrate that PR encapsulation potentiates the efficacy of NAC, likely through enhanced cellular uptake and mitochondrial delivery, thereby preserving antioxidant defenses and mitochondrial function. Overall, PR-NAC shows promise as a broad-spectrum nanotherapeutic for oxidative stress-induced liver injury, although further in vivo investigation is required.
Methods: Cell viability was assessed using the MTT assay across increasing PQ concentrations, either alone or in combination with NAC or PR-NAC. Following determination of the PQ IC50 and evaluation of its interaction with safe doses NAC and PR-NAC, mitochondrial membrane potential (ΔΨm), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and catalase (CAT) activity were assessed.
Results: PQ exposure (IC50 = 17.47 µg/mL) significantly compromised cell membrane integrity, collapsed the ΔΨm, and SOD and CAT activities. PR-NAC provided greater protection than free NAC, shifting the PQ IC50 to 26.41 µg/mL and restoring ΔΨm to levels close to those of the control group. PR-NAC also increased SOD and CAT activities to a degree comparable to that of NAC.
Conclusion: These findings demonstrate that PR encapsulation potentiates the efficacy of NAC, likely through enhanced cellular uptake and mitochondrial delivery, thereby preserving antioxidant defenses and mitochondrial function. Overall, PR-NAC shows promise as a broad-spectrum nanotherapeutic for oxidative stress-induced liver injury, although further in vivo investigation is required.
Type of Study: Research |
Subject:
Special
Received: 2026/11/14 | Accepted: 2027/03/1 | Published: 2026/11/14
Received: 2026/11/14 | Accepted: 2027/03/1 | Published: 2026/11/14
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