Protective effect of green synthesized Selenium Nanoparticles against Doxorubicin induced multiple adverse effects in
Mohammad Afsar Khan1, Deepti Singh1, Amin Arif2
1Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India.
Aims:
Doxorubicin (DOX) is a widely used drug against multiple cancers. However, its clinical Use is often restricted due to multiple adverse effects. Recently, Selenium Nanoparticles (SeNPs) are gaining attention due to their low toxicity and higher biocompatibility, making them attractive nanoparticles (NPs) in medical and pharmaceutical sciences. Therefore, the current study aimed to assess if our biosynthesized SeNP from the endophytic fungus Fusarium oxysporum conjugated with DOX could alleviate the DOX-induced adverse effects.
Main Methods:
For this purpose, we investigated various genotoxic, biochemical, histopathological, and immunohistochemical parameters and finally analyzed the metabolite profile by LC-MS/MS.
Key Findings:
We observed that DOX causes an increase in reactive oxygen and nitrogen species (ROS, RNS), 8-OHdG, and malondialdehyde (MDA), decreases antioxidant defense systems and reduces BCL-2 expression in cardiac tissue. In addition, a significant increase in DNA damage and alteration in the cytoarchitecture of the liver, kidney, and heart tissues was observed by Comet Tail Length and histopathological studies, respectively. Interestingly, the DOX-SeNP conjugate reduced ROS/RNS, 8-OHdG, and MDA levels in the liver, kidney, and heart tissues. It also restored the antioxidant enzymes and cytoarchitectures of the examined tissues, reduced genotoxicity, and increased the BCL-2 levels. Finally, metabolic profiling showed that DOX reduced the number of cardioprotective metabolites, which DOX-SeNP restored.
Significance:
Collectively, the present results describe the protective effect of DOX-conjugated SeNP against DOX-induced toxicities. In conclusion, DOX-SeNP conjugate might be better for treating patients receiving DOX alone. However, it warrants further thorough investigation.
Insights
Selenium nanoparticles conjugated with Doxorubicin (DOX-SeNP) show protective effects against DOX-induced toxicities. This novel conjugate may offer a safer alternative for cancer patients, warranting further investigation.
Area of Science:
- Biomedical Science
- Nanotechnology
- Cancer Therapy
Background:
- Doxorubicin (DOX) is a vital chemotherapy drug, but its use is limited by severe adverse effects.
- Selenium Nanoparticles (SeNPs) offer low toxicity and high biocompatibility, making them promising for medical applications.
Purpose of the Study:
- To evaluate if biosynthesized SeNPs from Fusarium oxysporum, conjugated with DOX (DOX-SeNP), can mitigate DOX-induced adverse effects.
- To assess the protective potential of DOX-SeNP against genotoxicity, biochemical alterations, and histopathological damage.
Main Methods:
- Investigated genotoxic, biochemical, histopathological, and immunohistochemical parameters.
- Analyzed metabolite profiles using Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS).
Main Results:
- DOX increased oxidative stress (ROS, RNS, MDA), DNA damage (8-OHdG), and decreased antioxidant defenses and BCL-2 expression.
- DOX-SeNP conjugate significantly reduced oxidative stress, genotoxicity, and MDA levels.
- DOX-SeNP restored antioxidant enzymes, cytoarchitecture in liver, kidney, and heart tissues, and increased BCL-2 levels.
Conclusions:
- DOX-SeNP demonstrates a protective effect against Doxorubicin-induced toxicities.
- The DOX-SeNP conjugate shows potential as an improved therapeutic option compared to DOX alone.
- Further comprehensive research is recommended to validate these findings for clinical application.
