The antioxidant, anti-inflammatory and anti-apoptotic effects of Cucumis melo var. agrestis Naudin in doxorubicin-induced hepatotoxicity and nephrotoxicity in rats
Jul 2026· Health Sciences Quarterly· 0 citations· 38 references
TL;DR
CM significantly attenuates DOX-induced hepatotoxicity and nephrotoxicity, particularly at a dose of 250 mg/kg, and its protective effects are likely mediated through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.
Abstract
This study investigated the protective effects of Cucumis melo var. agrestis Naudin (CM) at various doses against doxorubicin-induced liver and kidney injury in rats. Thirty male Wistar rats were randomly divided into five groups (n = 6 per group). DOX was administered intraperitoneally at a dose of 15 mg/kg on day 5. CM was administered orally at doses of 100, 250 or 500 mg/kg daily for ten consecutive days after DOX administration. Histological and immunohistochemical analyses were performed to evaluate tissue damage and the expression levels of caspase-3, HSP70, NF-κB p65 and TNF-α. Serum cytokines (IL-6, IL-1β, TNF-α and IL-10) and oxidative stress markers (TOS and TAS) were also measured. The DOX group exhibited significant liver and kidney damage, including hepatocellular degeneration, vascular congestion, and injury to the glomeruli and tubules, as well as increased immunoreactivity for Caspase-3, HSP70, NF-κB-p65, and TNF-α. The DOX+CM250 group showed a significant improvement in histological appearance and a marked reduction in immunoreactivity. Compared to the DOX group, this group also demonstrated decreased levels of pro-inflammatory cytokines and TOS, and increased IL-10 and TAS levels. CM significantly attenuates DOX-induced hepatotoxicity and nephrotoxicity, particularly at a dose of 250 mg/kg. Its protective effects are likely mediated through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.
Abbreviations: ALT – Alanine aminotransferase, AST – Aspartate aminotransferase, Bax – Bcl-2–associated X protein, Bcl-2 – B-cell lymphoma 2, BUN – Blood urea nitrogen, CM – Cucumis melo var. agrestis Naudin, DOX – Doxorubicin, GGT – Gamma-glutamyl transferase, GR – Glutathione reductase, GSH – Glutathione, HSP70 – Heat shock protein 70, IHC – Immunohistochemistry, IL – Interleukin, IL-1β – Interleukin-1 beta, IL-6 – Interleukin-6, IL-10 – Interleukin-10, MDA – Malondialdehyde, NF-κB – Nuclear factor kappa B, NF-κB p65 – Nuclear factor kappa B subunit p65, PCNA – Proliferating cell nuclear antigen, ROS – Reactive oxygen species, SOD – Superoxide dismutase, TAS – Total antioxidant status, TNF-α – Tumor necrosis factor alpha, TOS – Total oxidative status
Aim
DOX is a widely used chemotherapeutic agent, but its severe nephrotoxicity limits its clinical use. This study evaluates the potential protective effects of Solidago virgaurea extract against DOX-induced kidney damage in rats.
Methods
Animals were classified into four groups, with 8 rats in each group: control, extract-only, DOX, and DOX plus extract (DOX + Solidago virgaurea extract).
Results
After 14 days, DOX administration led to significant renal impairment, demonstrated by elevated serum Cr and BUN levels, along with histopathological disruption. DOX also induced oxidative stress by increasing MDA levels and reducing TAC. Furthermore, it triggered renal inflammation by upregulating pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β, while downregulating anti-inflammatory cytokines (IL-10, TGF-β, IL-35). Additionally, DOX promoted renal apoptosis by increasing the levels of apoptotic markers (Caspase-3, BAX) and decreasing the anti-apoptotic BCL-2 protein levels. Co-treatment with Solidago virgaurea extract effectively mitigated these adverse effects by reversing the previously observed changes in these parameters. Histopathological analysis further confirmed the preservation of renal architecture compared with the DOX-only group.
Conclusion
These results suggest that Solidago virgaurea extract exhibits strong nephroprotective potential, making it a promising adjunctive therapy for preventing chemotherapy-induced kidney injury.
Rehab M. Bagadood· The Annals of Clinical and A...· 0 citations
Rosmarinus officinalis extract may exert protective effects against MTX-induced hepatorenal injury through antioxidant and anti-inflammatory mechanisms, however, further studies are required to confirm these effects and validate their therapeutic potential.
Lana Muhammed, Nadia Salih· Open Veterinary Journal· 0 citations
Doxorubicin (DOX) is an anticancer antibiotic that is widely utilized. Nevertheless, this therapeutic potential is hampered by its cardiotoxicity. Alogliptin (ALO), an antidiabetic, recently is being repurposed for the management of various organs ailments owing to its discovered biological activities as an antioxidant, anti-inflammatory, anti-apoptotic and antifibrotic through multiple pathways. This study is directed to evaluate the possible protective effect of ALO against DOX-induced cardiac molecular and histopathological alterations. Twenty-four adult Wistar rats were grouped into control in addition to ALO (20 mg/kg, p.o, 21 days), DOX (18 mg/kg, i.p; six equal divided doses on alternative days starting at day 8), and Dox + ALO treated groups. On the 21st day, blood samples are collected to assess cardiac biomarkers. Additionally, the hearts of all rats were separated and processed for histological evaluation, ultrastructural examination, and collagen content determination by Masson Triciumus staining, and biochemical studies. The DOX group had pronounced deleterious histological and ultrastructural disorganization accompanied with abundant collagen disposition. Biochemically, DOX group demonstrated significant elevation of cardiomyocytes content of MDA, NF-κB, TNF-α, IL-6, BAX, and TGF-β1 which mirrored as significantly elevated serum LDH, CKMB, and cTnI levels. However, SOD and CAT activities as well as GSH, BCL-2, SIRT3 and NRF2 content along with miRNA-133a gene expression are significantly decreased. Present results proved the prophylactic ALO antioxidant, anti-inflammatory, anti-apoptotic, and anti-fibrotic influence on the DOX-induced cardiotoxicity with proposed mechanisms entailing the activation of SIRT3 pathway that may be governed by miRNA-133a. However, these results are limited by the inspection lack of echocardiography or hemodynamic alterations, gain and loss of function, caspase activation, and mitochondrial health tests. Thus, ALO has the potential to be an appropriate therapy for DOX-induced cardiotoxicity.
N. F. Elmongy, Mohamed Ali Abbas, S. Elshora et al.· Tissue & Cell· 0 citations
Pretreatment with PEIV significantly mitigated effects of LPS-induced liver injury by regulating biochemical parameters, reducing oxidative stress and inflammation, and preserving liver architecture, suggesting its potential as a natural therapeutic agent for liver diseases.
S. Anadozie, A³ Maryam, Theophilus I. Ebe et al.· Comparative Clinical Patholo...· 0 citations
Nano MOLE could be used as a therapeutic agent against hepatic toxicity induced by Cd in rats owing to its antioxidant and anti-inflammatory potential, and the low dose of Nano MOLE is much better to be used to avoid the deleterious effect of accumulation in the body organs and the resulted inflammation.
Abdeldayem Zakaria, Abdel-hasseb Fayed, S. Hedaya et al.· Alexandria Journal of Veteri...· 0 citations
Purpose: To investigate the effect of taxifolin in sepsis-induced renal injury.Methods: A total of 24 adult male Swiss albino mice were randomly and equally assigned to 4 groups (n = 6). Group 1 was the control (exposed to abdominal laparotomy without cecal ligation and puncture (CLP) procedure), group 2 underwent CLP with no treatment, and groups 3 and 4 received intraperitoneal DMSO and taxifolin (10 mg/kg), respectively, 1 h before the CLP procedure. Renal function, NF-κB, MDA levels, Nrf2 expression, and caspase-3 activity were evaluated.Results: Sepsis induced by CLP led to significant deterioration of renal function, characterized by higher serum creatinine and renal KIM-1, including severe histopathological kidney damage. Sepsis induced by CLP increased NF-κB and MDA levels, downregulated Nrf2 expression, and elevated caspase-3 activity. Taxifolin administration significantly mitigated these alterations, enhanced renal function and histological architecture, suppressed oxidative damage and the inflammatory response, and restored Nrf2 signaling.Conclusion: Taxifolin conferred a substantial renoprotective effect against acute kidney impairment induced by sepsis by reducing inflammatory responses, oxidative stress, and preserving tubular structural integrity.
Alaa Q. Aldhaheri, Ali M. Janabi· Tropical Journal of Pharmace...· 0 citations
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