Avicenna Journal of Pharmaceutical Research

en Polyrhodanine Nanoencapsulation Potentiates N-Acetylcysteine Against Paraquat-Induced Cytotoxicity in HepG2 Cells تخصصي Special پژوهشي Research 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.   Paraquat, Polyrhodanine, N-acetylcysteine, Oxidative stress, HepG2 81 87 http://ajpr.umsha.ac.ir/browse.php?a_code=A-10-2-88&slc_lang=en&sid=1 Yekta Kheradmand No 1 Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Davoud Ahmadimoghaddam No 1 Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Fatemeh Ghaffari No 1 Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Seyyed Alireza Hashemi No 4 Health Policy Research Center, Health Institute, Shiraz University of Medical Sciences, Shiraz, Iran Navid Omidifar No 5 Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Amir Nili-Ahmadabadi a.niliahmadabadi@umsha.ac.ir Yes 1 Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran