PVP- coated naringenin nanoparticles for biomedical applications – In vivo toxicological evaluations
Authors: Annie Abraham
R Pradeep Kumar
Journal: Chemico-Biological Interactions (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Antioxidant enzymes; Inflammatory markers; Nanoparticles; Naringenin; Naringenin (PubChem CID: 932)
Affiliations: Centre for Nanoscience and Nanotechnology, Kariavattom Campus, University of Kerala, Thiruvananthapuram, Kerala, India. Electronic address: ., Department of Biochemistry, Kariavattom Campus, University of Kerala, Thiruvananthapuram, Kerala, India. Electronic address: .

Abstract:  Naringenin (NAR) is one of the naturally occurring flavonoids found in citrus fruits and exerts a wide variety of pharmacological activities. The clinical relevance of naringenin is limited by its low solubility and minimal bioavailability, owing to its largely hydrophobic ring structure. The aim of the present study is to develop a novel naringenin nanoparticle system (NAR NP) using simple nanoprecipitation technique with polyvinylpyrrolidone (PVP) as the hydrophilic carrier. The synthesized nanoparticles were characterized using XRD, FTIR, SEM and EDX. The characterization study revealed the nanoscale properties and the interactions between NAR and PVP. In vivo toxicological evaluations were carried out at various doses (1, 5, 10 &amp; 50 mg/kg body wt) in male Sprague-Dawley rats in comparison with silver nanoparticle (AgNP) at toxic concentration (50 mg/kg body wt). The altered hepatotoxicity markers, hematology parameters and antioxidant defense system were observed in AgNP- treated rats. But NAR NP - treated rats did not show any biochemical alterations and improved the antioxidant defense indices when compared to control group, by virtue of the pharmacological properties exerted by NAR. The modulatory effect of NAR NP over inflammatory and stress signaling cascades were confirmed by the normalized mRNA expressions of NF-κB, TNF-α and IL-6. The histopathological analysis of liver, kidney and heart reinforce our findings. These studies provide preliminary answers to some of the key biological issues raised over the use and safety of nanoparticles for diagnostic and therapeutic applications. Consequently, we suggest that the safe NAR NP can be used to reduce the dosage of NAR, improve its bioavailability and merits further investigation for therapeutic applications. 

Retracted: No

PubPeer comments:
 Thank you for the corrections noted in the figure 9. Its a mistake due to manual error. This error has occurred, while sorting the multiple histology pictures from same groups and different groups. We really apologize for this mistake. We hope this will not affect the findings of the paper, since there were no toxicity changes noted in nanoparticle treated groups as evident from other results. We will try to correct the mistakes. For figure 8 and Table 3, there is no overlapping. The picture resolution issue in the figure 8 is due to the instrumental settings . The similar values in Table 3 are the original mean of the respective groups. Again we apologize for the mistake and appreciate for your comment. , 
 #2 Thank you for your reply. Could you please post the original uncropped scans for the blots in Figure 8 and the raw data for Table 3? The original data will undoubtedly resolve my concerns. , 
 For fig 8: The imaging of the band area of agarose electrophoretic gels were done using BioRAD UNIVERSAL HOOD II GEL DOCUMENTATION system and the intensity of the resulting cropped bands were analyzed using Image Quant software which is inbuilt in the same instrument. So we don t have the picture of the whole gel. Since this experiment was performed as a part of our initial study, currently we don t have access to most of the raw data files. But still, the raw Excel data for Table 3 is available, which I can send you if you provide your mail id. Because I couldn t upload Excel file here due to file format issue. Thanks. , 
 Overlapping images in Figure 9. Arrows in the images below were in the original Figure. *** Kidney ![file] *** Heart ![file] , 
 Dear Dr. Pradeep Kumar, Figure 9, as noted above by Actinopolyspora Biskrensis, has at least five errors. How can you state that this does not affect the findings of the paper? In my opinion, it means that your lab is not good in keeping track of which experiment is linked to which data, so I would be very worried about the rest of the data reported in this paper. Then, your explanation about the gel images in Figure 8 in comment #4 does not make sense. It is not the Gel Doc system (which is basically a video camera mounted in a big box) that determines the layout of an image, it is the user. So it is a user choice how to take the photos. I have always learned to take gel photos with not only the bands, but also the lanes visible. I share AB s concerns about the gel images in Figure 8; the bands s placements in the gel looks unnatural. Even if you do not have uncropped scans, I am sure you could share the scans used to create the gel composites in Figure 8. Regarding Tables 2 and 3, I too have concerns. Could you please upload the Excel data publicly through Google Docs (should be easy since both corresponding email addresses are at Gmail) or another file sharing tool? ,