Palladium chloride-induced testicular damage in rats: Histopathology, oxidative stress, ER stress, and Nrf2/HO-1 signaling and the protective role of quercetin.
Aug 2026· Tissue & Cell· Vol 104 Pt 1, pp.
103855
· 0 citations· 85 references
Medicine
TL;DR
Overall, the findings indicate that Que mitigates PdCl₂-induced testicular injury, and that this protection may be associated with antioxidant, anti-inflammatory, anti-apoptotic, ER stress-related, and Nrf2/HO-1-associated responses rather than direct proof of pathway activation.
Abstract
The present study aimed to evaluate the protective potential of quercetin (Que), a flavonoid recognized for its antioxidant and anti-inflammatory activities, against palladium chloride (PdCl₂)-induced testicular toxicity. Twenty-four male Wistar rats were assigned to Control, Que (30 mg/kg), PdCl2 (8 mg/kg), and Que + PdCl2 groups for 28 days. PdCl₂ exposure was associated with reduced serum testosterone, LH, and FSH levels, impaired sperm quality, histopathological injury, increased oxidative stress and oxidative DNA damage, and diminished antioxidant capacity. These changes were accompanied by reduced Nrf2 and HO-1 levels, increased IL-6 and IL-1β concentrations, enhanced TNF-α immunoreactivity, and increased immunoreactivity of apoptosis and ER stress-related markers. Que co-treatment partly counteracted these alterations, improving redox balance, hormone levels, sperm parameters, and tissue morphology. Overall, the findings indicate that Que mitigates PdCl₂-induced testicular injury, and that this protection may be associated with antioxidant, anti-inflammatory, anti-apoptotic, ER stress-related, and Nrf2/HO-1-associated responses rather than direct proof of pathway activation.
BACKGROUND
The nephrotoxicity induced by cisplatin (Cis) is mediated by oxidative stress, inflammation, and apoptosis, which limit the clinical utility of this commonly used chemotherapeutic drug. Natural polyphenolic compounds such as quinic acid (QA) have cytoprotective and antioxidant properties. This study evaluated the protective effect of QA against cisplatin-induced acute kidney injury (AKI) in rats and its impact on the associated oxidative, inflammatory, apoptotic, and Nrf2/HO-1/NQO1 pathways.
METHODS
Forty male Wistar rats were randomly divided into five groups (n = 8): Control, Cis (7.5 mg/kg, i.p.), Cis + QA was administered orally at doses of 25, 50, or 100 mg/kg once daily for 14 days before the cisplatin challenge. Biochemical markers (BUN, creatinine, KIM-1, NGAL), oxidative stress indices (MDA, NO, GSH, TAC, SOD, CAT, GPx), inflammatory cytokines (TNF-α, IL-1β), apoptotic gene expression (Bax, Bcl-2, Caspase-3), and Nrf2 pathway proteins (Nrf2, HO-1, NQO1) were assessed. Renal histopathology was evaluated using blinded scoring.
RESULTS
Cisplatin caused severe renal dysfunction, oxidative imbalance, inflammation, and apoptosis, along with the suppression of Nrf2/HO-1/NQO1 signaling. QA, particularly at doses of 50 and 100 mg/kg, significantly improved serum renal markers, restored antioxidant capacity, reduced MDA and NO levels, downregulated TNF-α and IL-1β, modulated apoptotic gene expression toward cell survival, and enhanced Nrf2-pathway protein levels. Histological injury scores were significantly lower in groups treated with QA.The antioxidant, anti-inflammatory, anti-apoptotic, and Nrf2-pathway-modulating properties of quinic acid markedly attenuate cisplatin-induced AKI. Further mechanistic and translational research on QA to evaluate its potential as a nephroprotective adjunct is warranted.
Mehdi Goudarzi, Z. Lamoochi, Susan Sabbagh et al.· Immunopharmacology and immun...· 1 citation
This study aimed to investigate the effect of hesperidin (HSP) at two different doses on deltamethrin (DLM)-induced testicular damage. The study comprised four groups of Wistar Albino rats (n = 8 per group): Control, DLM, DLM + HSP 100 mg/kg, and DLM + HSP 300 mg/kg. At the end of the study, oxidative stress markers and CRP were measured in serum samples. Testicular tissues were assessed histopathologically. Expression of Bcl-2, Bax, and Nrf-2 were determined by immunofluorescence staining. RT-qPCR assessed tissue collagen (COL1A1, COL3A1) and apoptotic () expressions. HSP at both doses lowered the DLM-induced increase in total oxidant status, oxidative stress index (total oxidant status/total antioxidant capacity), and CRP levels. Nrf-2 was increased by a high dose of HSP (300 mg/kg). Whereas HSP normalized other apoptotic parameters at both doses, it partially normalized Bax expression in immunofluorescence and Bcl-2 expression in RT-qPCR only at 300 mg/kg. HSP reduced the increased fibrosis in DLM exposure, as revealed by the expressions of COL1A1 and COL3A1 at both doses. HSP partially ameliorated DLM-associated histological alterations, including Johnsen’s score, tubule diameter, and thickness of the tunica albuginea. HSP may exert protective effects against DLM-induced testicular injury by modulating systemic oxidative status, apoptosis-associated signaling, and profibrotic gene expression.
Investigating the protective effects of OLE against ACR-induced reproductive toxicity in male and female rats indicates that OLE exerts a significant cytoprotective effect through its antioxidant and anti-apoptotic properties, with the extent of protection varying across tissue types.
Nevzat Saat, E. Aksu, M. Tatar et al.· Journal of Molecular Histolo...· 0 citations
Objective(s): This study aimed to assess the protective role of hesperidin (HSP), a citrus flavonoid, against di-(2-ethylhexyl) phthalate (DEHP)-induced kidney toxicity in rats, focusing on oxidative stress, apoptosis, inflammation, and anti-oxidant defense pathways. Materials and Methods: Thirty-five male rats were randomly assigned into five groups (7 per group): control group, DEHP-treated group (1 g/kg), DEHP + HSP (100 mg/kg) group, DEHP + HSP (200 mg/kg) group, and HSP-alone group, and treated orally for 10 consecutive days. Kidney tissues were collected for biochemical assays, including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Gene expression of Nrf2, Keap1, HO-1, Bax, Bcl-2, Caspase-3, TLR-4, and NF-κB was analyzed using real-time PCR, and protein levels were evaluated using Western blotting. Results: DEHP significantly increased oxidative damage and the expression of inflammatory and apoptotic markers, while decreasing anti-oxidant parameters. Co-treatment with HSP, particularly at 200 mg/kg, restored anti-oxidant balance, reduced lipid peroxidation, and down-regulated the expression of TLR-4, NF-κB, and Caspase-3. Moreover, HSP increased Bcl-2 levels and enhanced Nrf2/HO-1 signaling, as confirmed by both gene and protein expression data. Conclusion: HSP demonstrates dose-dependent renoprotective effects against DEHP-induced nephrotoxicity in rats. 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
Phthalates, including dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), are widely used plasticizers associated with male reproductive toxicity. This study evaluated the dose- and temporal-dependent effects of DBP and DEHP (100, 200, and 400 mg/kg for 15 days) on testicular structure and function in immature Swiss albino mice at 36, 45, 50, and 70 days of age. Biochemical analyses revealed significant glutathione depletion accompanied by increased nitric oxide and lipid peroxidation levels, suggesting oxidative imbalance. Histological evaluation demonstrated severe dose-dependent testicular injury, particularly at 36–45 days, with the 400 mg/kg groups showing 100% damaged seminiferous tubules and marked reductions in Johnsen’s scores (3.5 ± 0.17 vs. 9.9 ± 0.10 in controls). Increased Caspase-3 and NF-κB expression suggested possible involvement of apoptotic and inflammatory responses. Longitudinal assessment from 50 to 70 days revealed a dose-dependent recovery pattern, with substantial restoration in lower-dose groups, whereas higher doses remained associated with persistent tubular damage at 70 days (47.0% in DBP and 58.8% in DEHP groups). These findings suggest that the severity of testicular injury and the extent of recovery are influenced by phthalate exposure dose. Therefore, further studies are required to fully understand the underlying molecular mechanisms.
R. Ali, Heba E. Aboulqasem, Dalia Elzahraa F. Mostafa· Scientific Reports· 0 citations
