Attenuation of diethylnitrosamine (DEN) – Induced hepatic cancer in experimental model of Wistar rats by Carissa carandas embedded silver nanoparticles
Authors: Deepika Singh
Vikas Kumar
Manvendra Singh
Neha Falls
Deependra Singh Dangi
Pramod W Ramteke
Ekta Yadav
Amita Verma
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Carissa carandas embedded silver nanoparticles; Hepatocellular carcinoma; NF-κB pathway.
Affiliations: Bio-Organic & Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, 211007, Uttar Pradesh, India. Electronic address: ., HMFA Institute of Engineering & Technology, Handia, Allahabad, 211007, India., Bio-Organic & Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, 211007, Uttar Pradesh, India., Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, 211007, India., Kinapse India Scientific Services Pvt. Ltd., Gurgaon, Haryana, India., Department of Biological Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, 211007, India.

Abstract:  Objective: Hepatic cancer is well known, and leading cancer around the world and remain asymptomatic diseases. Carissa carandas possess anti-proliferative, antioxidant, hepatoprotective property and used in hepatic cancer. The current study deals to evaluate the chemoprotective and therapeutic property of Carissa carandas embedded silver nanoparticles (CCAgNPs) against diethylnitrosamine (DEN) -induced hepatic cancer. Material and method: Wistar rats were divided into six groups and hepatic cancer was induced with diethylnitrosamine at the dose of 200 mg/kg BW. The animals were gastrogavaged with standard drug and CCAgNPs for 16 weeks. Serum biomarkers, haematological profile, antioxidants enzymes, inflammatory markers and membrane bound enzymes were assessed to find the anti-proliferative potential of silver nanoparticles. Histological evaluation and microscopic characterizations were also performed to authenticate the outcomes of the present work. Results: Biosynthesized CCAgNPs significantly down-regulated the serum marker enzymes of hepatic and non-hepatic parameter, elevated the levels of enzymatic and non-enzymatic antioxidant profile, elevation in membrane bound enzymes and diminish the levels of inflammatory markers (IL-6, TNF-α, and IL-1β) via NF-κB pathway. Histopathological features also showed recovery of a hepatic architecture in cancer-induced rats in a dose-dependent manner. Conclusion: Our consequences established that such plant mediated silver nanoparticles shown a defensive impact against DEN-induced hepatocarcinogenesis, and serves as a better option to ameliorate the clinical results against hepatocellular carcinoma. 

Retracted: No

PubPeer comments:
 Figure 9a (normal control) overlaps with Figure 15f (DEN-induced + Silymarin) of another paper by the same group published a year later (blue boxes). Images have different vertical sizes. Could the authors please comment? ![file] , 
 * DEN initiated hepatocarcinogenesis in rat, is a standout amongst the most acknowledged animal models for hepatic cancer, which permits to determine the anticancer agents on various periods of neoplastic change and development [22]. [22] Y. Liu, M. Liu, B. Li, J.L. Zhao, C.P. Zhang, L.Q. Lin, H.S. Chen, S.J. Zhang, J.C. Jin, L. Wang, L.J. Li, J.R. Liu, **Fresh raspberry** phytochemical extract inhibits hepatic lesion in a wistar rat model, Nutr. Metabol. 7 (2010), https: doi.org 10.1186 1743-7075-7-84 84. Could the authors please elaborate on the relevance of this reference in the context? , 
 I have added some annotations via Hypothes.is [here] . Some of the problems: * The first sentence of the abstract.  Hepatic cancer [u2026] remain asymptomatic diseases. !! * Lots of unsubstantiated claims in the introduction (without references). * The  standard drug to which the silver NPs are compared is not a standard anticancer drug (it is not an anticancer drug). * The numbers of animals don t add up (36 animals total, but 4 groups of 3 for the tox study, and 5 groups of 6 for the main experiments, so that 42 total). * The numbers in table 3 don t make sense. There are 6 rats in each group. If the total number of nodules is 110 for the DEN group, then the average should be 110 6 = 18.3, not 58.78. Where does this number comes from? These average number of modules don t make sense. For example, for the last line, it is impossible to 9.98 by averaging 6 positive integers. The closest to 10 you could get would be by having 10, 10, 10, 10, 10 and 9, average 9.83. ,