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Protective effect of deinoxanthin in sorafenib-induced nephrotoxicity in rats with the hepatocellular carcinoma model
Nilgun Karasu1,2, Mehmet Kuzucu3, Ozge Cengiz Mat4
1Faculty of Medicine, Department of Medical Genetics, Erciyes University, Kayseri, Turkey.
Abstract:
Sorafenib is a synthetic compound and an orally administered multichines inhibitor that targets growth signaling and angiogenesis. It is widely recognized as the standard of care for advanced hepatocellular carcinoma (HCC) but has toxic side effects. Deinoxanthin, purified from the radioresistant bacterium Deinococcus radiodurans, has strong antioxidant characteristics. In this study, the protective effect of deinoxanthin against sorafenib-induced nephrotoxicity was investigated in a rat model of hepatocellular carcinoma. In this regard, the expressions of DDAH1, KIM1, and INOS genes were examined, histopathological and immunohistochemical analyses were performed, and various parameters such as SOD, MDA, GST, CAT, TAS, and TOS were tested biochemically. BUN and creatinine levels were measured in renal tissues. RT-qPCR, Western blot, and ELISA methods were used for all these analyses. As a result, the analyses show that deinoxanthin, which has a high antioxidant capacity, reduces kidney injury and can be used as a protective agent. The primary objective of this study is to evaluate the potential of deinoxanthin as a protective agent against the nephrotoxic side effects of sorafenib in HCC. Our study identified the potential synergistic effects of sorafenib and deinoxanthin on nephrotoxicity in rats with hepatocellular carcinoma.
Insights
Deinoxanthin, an antioxidant from Deinococcus radiodurans, protects against kidney damage caused by sorafenib, a cancer drug. This study suggests deinoxanthin could mitigate sorafenib
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Sorafenib is a standard treatment for advanced hepatocellular carcinoma (HCC) but causes toxic side effects, including kidney damage.
- Deinoxanthin, a potent antioxidant from Deinococcus radiodurans, is being investigated for its protective properties.
Purpose of the Study:
- To evaluate deinoxanthin's protective effect against sorafenib-induced nephrotoxicity in a rat model of HCC.
- To explore the potential synergistic effects of sorafenib and deinoxanthin on kidney function.
Main Methods:
- Biochemical assays (SOD, MDA, GST, CAT, TAS, TOS), BUN, and creatinine levels were measured.
- Gene expression analysis (DDAH1, KIM1, INOS) using RT-qPCR.
- Histopathological and immunohistochemical analyses, Western blot, and ELISA were performed.
Main Results:
- Deinoxanthin demonstrated significant antioxidant capacity, reducing kidney injury markers.
- Biochemical and molecular analyses indicated a protective role of deinoxanthin against sorafenib toxicity.
- Histopathological findings supported the renoprotective effects of deinoxanthin.
Conclusions:
- Deinoxanthin exhibits potential as a protective agent against sorafenib-induced nephrotoxicity in HCC.
- The findings suggest deinoxanthin could be a valuable adjunct therapy to mitigate side effects of sorafenib treatment.
- Further research is warranted to explore the clinical application of deinoxanthin in cancer therapy.
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