Results indicate that mangiferin confers nephroprotection against TAC-induced renal injury that is highly associated with the modulation of oxidative stress, NLRP3 inflammasome, VEGF signaling, and PI3K/AKT/PTEN-mediated autophagy and apoptosis.
Naif S. Alharbi, Omnia Nour, M. Makled et al.· Naunyn-Schmiedeberg's Archiv...· 0 citations
The protective mechanism involves anti-oxidant enhancement and inhibition of oxidative stress-induced inflammation and apoptosis, supporting the therapeutic potential of HSP in managing phthalate-related renal injury.
Tuba Karaarslan, B. Yıldırım, F. Yildirim et al.· Iranian Journal of Basic Med...· 0 citations
BACKGROUND
Podophyllotoxin (PPT) has antitumour activity but may cause nephrotoxicity through incompletely defined mechanisms.
METHODS
Male Sprague-Dawley rats received oral PPT (5 or 10mg/kg/day) for 5 days. Renal injury was evaluated by biochemical, histopathological, Raman, metabolomic, transcriptomic, targeted proteomic, and molecular analyses, followed by validation in NRK-52E cells.
RESULTS
PPT at 10mg/kg reduced 24-h urine output (p < 0.05) and increased serum urea (p < 0.05), uric acid (p < 0.001), KIM-1 (p < 0.001), and lipocalin-2 (p < 0.0001). Renal GSH and CAT decreased (p < 0.001 and p < 0.01, respectively), accompanied by tubular injury, collagen deposition, and apoptosis. Trpm2 and inflammatory and matrix-remodelling genes were upregulated. PRM identified reduced LDHC, HK3, and MGST2 abundance. JNJ-28583113 attenuated PPT-induced ROS accumulation, apoptosis, Nod1/Nod2 expression, and NF-κB p65 phosphorylation.
CONCLUSION
PPT induces subacute kidney injury involving oxidative stress and TRPM2-NOD-NF-κB-related inflammatory signalling.
Lulu Chen, Zilong Chen, Xinze Li et al.· Environmental Toxicology and...· 0 citations
Arsenic trioxide (ATO) is a potent therapeutic agent against acute promyelocytic leukemia; nevertheless, its clinical utility is severely restricted by dose-limiting nephrotoxicity. This study investigated the protective potential of a radiation-synthesized gallotannin hydrogel (GTH) against ATO-induced kidney injury in rats. Forty male Wistar rats were randomized into four experimental groups: Control, ATO (4 mg/kg, i.p., for 4 weeks), GTH (2 mg/kg, i.p.), and ATO + GTH. GTH treatment was initiated during the third week of ATO administration, with GTH being administrated one hour prior to ATO injection. Following the experimental period, animals were sacrificed, tissue histology was examined, and renal function was assessed by serum urea and creatinine levels. Oxidative stress was evaluated via MDA, SOD, GSH, and GPx markers. Additionally, miR-223 and TXNIP expression levels were quantified using qRT-PCR. Inflammatory mediators (NF-κB, NLRP3, Caspase-1, IL-1β, and IL-18), endoplasmic reticulum (ER) stress markers (PERK, eIF2α, and CHOP), and the apoptotic marker caspase-3 were analyzed by ELISA. Our results revealed that GTH noticeably ameliorated kidney dysfunction, as evidenced by reduced serum urea and creatinine levels. Furthermore, GTH attenuated oxidative stress by decreasing MDA levels and restoring antioxidant enzyme activities (SOD, GSH, and GPx). Histological analysis confirmed that GTH mitigated structural renal damage. Molecularly, GTH administration suppressed the ATO-induced upregulation of miR-223 and TXNIP. This downregulation correlated with a reduction in inflammatory mediators, attenuation of ER stress markers, and decreased apoptosis. These findings demonstrate that radiation-synthesized gallotannin hydrogel (GTH) exerts nephroprotective effects against ATO-induced nephrotoxicity. These benefits are driven by antioxidant, anti-inflammatory, and anti-apoptotic mechanisms mediated via modulation of the miR-223/TXNIP axis.
Omayma A. R. Abo-Zaid, Mostafa A. Farrag, Aya S. R. Shaaban et al.· Biological Trace Element Res...· 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
Thioacetamide (TAA) induces renal injury via oxidative stress and inflammation. Remogliflozin (Remo), an SGLT2 inhibitor, was evaluated for potential renoprotection. Twenty-four male Wistar rats were assigned to control, TAA (100 mg/kg IP twice weekly), TAA + Remo 25 mg/kg, or TAA + Remo 50 mg/kg (oral daily). Outcomes included renal function, oxidative stress (GSH, SOD, MDA), antioxidant biomarkers (Nrf2, HO-1), inflammatory mediators (TLR4/NF-κB, TNF-α, IL-1β), metabolic/kinase biomarkers (SIRT1, AMPK, PI3K, AKT), and histopathology/immunohistochemistry (mTOR, MYD88, Nrf2). Remogliflozin was associated with lower serum creatinine, urea, and uric acid, with endpoint-specific differences between doses. Remo was associated with higher renal Nrf2, HO-1, SIRT1, and p-AMPK, and lower MDA, TLR4, NF-κB, TNF-α, IL-1β, PI3K, and AKT. Histopathology and IHC showed associations with reduced tissue injury, lower mTOR and MYD88 immunoreactivity, and increased Nrf2 staining. While the 50 mg/kg group showed changes in more markers, this does not establish uniform dose superiority or a formal dose-response relationship; at 25 mg/kg, effects differed among AMPK-related endpoints. Direct 25-versus-50 mg/kg comparisons were included in the Tukey-Kramer analysis for each endpoint. No pharmacokinetic measurements or formal dose-response analyses were performed. In this exploratory model, remogliflozin was associated with attenuation of TAA-induced renal injury and modulation of related biomarkers. Causal mechanisms remain to be confirmed by targeted intervention studies. Findings are limited to young male Wistar rats and should not be generalized to other populations or clinical settings. Remogliflozin warrants further preclinical investigation in TAA-associated renal injury.
Marwa M. Qadri, D. Almarghalani, Abdulaziz Alarifi et al.· Toxicology Mechanisms and Me...· 0 citations
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