Punicalagin Ameliorating Renal Cell Tumors Against N-Diethylnitrosamine-initiated Iron Nitrilotriacetate-induced Carcinogenesis

ABSTRACT

Background: Renal cell carcinoma, the most prominent kind of adult kidney cancer, lacks early warning symptoms, leading to metastases at the time of diagnosis. Renal cell carcinoma begins with N-diethylnitrosamine (DEN) and is accelerated by ferric nitrilotriacetate (Fe-NTA), which may be a good research model for renal cell carcinoma. Purpose: This study was designed to unveil the protective potential of punicalagin against renal cell tumors induced by Fe-NTA in male mice. Materials and Methods: Renal cancer initiation was achieved through a single intraperitoneal injection of DEN (200 mg/kg body weight (b.wt.)), followed by promotion using Fe-NTA (9 mg Fe/kg b.wt. intraperitoneally) administered twice weekly over 16 weeks. Simultaneously, mice were subjected to punicalagin (10 mg/kg b.wt.) for an uninterrupted 16-week duration. The chemopreventive efficacy of punicalagin was assessed by evaluating antioxidant activities, oxidative stress markers, renal function parameters, histopathological examinations, and immunohistochemical analyses. Results: Results showed a significant reduction in DEN and Fe-NTA-mediated lipid peroxidation, concurrent with the amelioration of renal function, as reflected by diminished levels of blood urea nitrogen, creatinine, and kidney injury molecule-1 in punicalagin-treated mice. Furthermore, punicalagin restored the renal antioxidant parameters like superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione in DEN and Fe-NTA-treated mice. Further, it was observed that punicalagin reduces the expression of 8-hydroxy-2′-deoxyguanosine (levels and 4-hydroxy-2-nonenal-modified protein adducts within the kidney tissue. Conclusion: These findings were further substantiated by histological examinations. Our current findings indicate that punicalagin might be a potential contender for preventing renal cancer, likely due to its capacity to reduce oxidative stress in laboratory animals.

KEYWORDS

• Punicalagin
• oxidative stress
• lipid peroxidation
• renal cancer
• chemoprevention

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• DOI10.1177/09731296241255436Copy

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