Protective Effects of Limonene and a Nano-Liposomal Limonene Formulation Against Chlorfenapyr-Induced Renal Toxicity: Mechanistic Insights into NRF2/HO-1 and NF-κB/COX-2 Signaling, Mitochondrial Dysfunction, and Apoptosis in Rat Kidneys
Overall, nano-liposomal delivery enhanced the renoprotective efficacy of limonene, highlighting its potential as a therapeutic strategy against pesticide-induced kidney injury.
Abstract
Chlorfenapyr (CFP) is a widely used pesticide associated with nephrotoxicity through oxidative stress, inflammation, and mitochondrial dysfunction. This study investigated the protective effects of limonene (LM) and its nano-liposomal formulation (LM-LNPs) against CFP-induced renal injury in rats. Animals were divided into six groups—control, LM, LM-LNPs, CFP, CFP + LM, and CFP + LM-LNPs—and treated orally for 30 days. CFP exposure resulted in marked renal dysfunction, histopathological and ultrastructural damage, suppression of the NRF2/HO-1/NQO1 antioxidant pathway, depletion of endogenous antioxidants excessive generation of reactive oxygen and nitrogen species, lipid peroxidation products, and DNA damage. These changes were accompanied by activation of NF-κB/COX-2-mediated inflammation, mitochondrial respiratory impairment, disrupted energy metabolism, and induction of apoptosis. Co-treatment with LM significantly ameliorated these alterations, whereas LM-LNPs produced greater improvements in renal function, tissue architecture, redox homeostasis, mitochondrial function, and inflammatory and apoptotic signaling. Immunohistochemical analyses further confirmed enhanced NRF2 expression and reduced NF-κB immunoreactivity in LM-LNP-treated kidneys. Overall, nano-liposomal delivery enhanced the renoprotective efficacy of limonene, highlighting its potential as a therapeutic strategy against pesticide-induced kidney injury.
N-Cur mitigates oxidative damage and inflammation, thereby preserving hepatic function during CDDP-based chemotherapy, and demonstrates significant potential as a hepatoprotective agent when administered concomitantly with CDDP chemotherapy.
Q. Alqahtani, M. Atteya, T. Almatrafi et al.· Biomedicines· 0 citations
Overall, RA‐loaded Chitosan nanoparticles provided superior protection against CFP‐induced testicular toxicity compared with crude RA, highlighting the potential of nanoformulation strategies to enhance RA's biological efficacy.
Ahmad Najem Alshammari, Ayat B. Al-Ghafari, H. A. Al Doghaither et al.· Journal of biochemical and m...· 0 citations
Cardiovascular diseases are increasingly linked to environmental toxicants, including widely used organophosphate pesticides. This study investigates the cardiotoxic potential of chlorpyrifos (CPF) and dimethoate (DM) using complementary in vivo and in vitro models. Female Wistar rats were orally exposed to CPF, DM and their combination for 30 days. Histopathological analyses revealed myocardial disarray, interstitial edema, inflammatory infiltration and aortic endothelial disruption, with combination group showing the most severe injury. Haematological alterations including reduced RBC and haemoglobin, elevated leukocyte and platelet counts were accompanied by significantly increased hydroxyproline content in heart and aorta, indicating early fibrotic remodelling. Molecular analysis demonstrated marked upregulation of NF-κB, NLRP3, IL-1β, IL-18 and TNF-α, along with suppression of eNOS, confirming activation of NF-κB/NLRP3 inflammasome axis and endothelial dysfunction. In vitro, CPF but not DM reduced endothelial cell viability and induced ROS generation and lactate dehydrogenase (LDH) release in HUVECs. CPF also elevated inflammatory and cell adhesion markers while downregulating eNOS and tight-junction proteins. Notably, NLRP3 inhibition by MCC950 mitigated CPF-induced inflammatory signaling and restored endothelial function. Collectively, these findings demonstrate that CPF and DM exposure induces cardiovascular injury mediated through oxidative stress, inflammasome activation and nitric oxide dysregulation, highlighting NLRP3 as a potential therapeutic target in pesticide-associated vascular toxicity.
Jasmeena Jan, Salman Shamas, Wajid Mohammad Sheikh et al.· Journal of Applied Toxicolog...· 0 citations
FSN-LNPs provided enhanced hepatoprotection against DEHP-induced toxicity compared with free FSN, which was associated with attenuation of oxidative stress and inflammation and modulation of apoptosis- and ferroptosis-related pathways, likely due to improved bioavailability and cellular delivery.
Ahmed Al-Emam, Hesham M. Hassan, E. Elmorsy et al.· Naunyn-Schmiedeberg's Archiv...· 0 citations
The antioxidant, anti-inflammatory, anti-apoptotic, and Nrf2-pathway-modulating properties of quinic acid markedly attenuate cisplatin-induced acute kidney injury in rats and its impact on the associated oxidative, inflammatory, apoptotic, and Nrf2/HO-1/NQO1 pathways.
Mehdi Goudarzi, Z. Lamoochi, Susan Sabbagh et al.· Immunopharmacology and immun...· 1 citation
Background: Oxidative stress is a major contributor to kidney dysfunction. Phloretin, a dietary flavonoid, exhibits antioxidant and anti-inflammatory activity. This study evaluated the protective effects of Phloretin against Bisphenol-A (BPA)-induced oxidative stress in human renal tubular epithelial (HK-2) cells.
Methods: HK-2 cells were exposed to BPA (1000 μM) for 24 hr with or without Phloretin (50, 100, 200 μM). Cell viability, oxidative stress markers Reactive Oxygen Species (ROS), Malondialdehyde (MDA), Total Antioxidant Capacity (TAC), cytokines (IL-6, IL-10), and VCAM-1/ICAM-1 expression were assessed.
Results: BPA markedly decreased cell viability and TAC while elevating ROS, MDA, IL-6, and VCAM-1/ICAM-1 expression (all p<0.001). Phloretin significantly reversed these effects in a dose-dependent manner. At 200 μM, Phloretin increased cell viability by ~35–40% (p<0.001), reduced ROS and MDA by ~35–40% (p<0.001), and restored TAC by ~40–45% (p<0.001) compared to BPA. Inflammatory markers were also modulated: IL-6 was reduced by ~35–40% (p<0.001), while IL-10 was elevated by ~40–45% (p<0.001). Moreover, Phloretin suppressed VCAM-1 and ICAM-1 expression by ~45–50% (p<0.001).
Conclusion: Phloretin significantly attenuates BPA-induced oxidative stress and inflammation in renal tubular cells, suggesting its potential as a natural nephroprotective agent.
M. Radan, Kousar Mirhashemi, Fereshte Nejaddehbashi et al.· Journal of Iranian medical c...· 0 citations
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