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Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 2, pp. 9-24
doi:10.32527/2017/101422

Evaluation of the Therapeutic Effects of Polyvinylpyrrolidone-Capped Silver Nanoparticles on the Diethylnitrosamine/Carbon Tetrachloride-Induced Hepatocellular Carcinoma in Rats

Samah M. Elaidy1, Amr Moghazy2, and Mohamed K. El-Kherbetawy3

1Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Egypt

2Department of Plastic Surgery, Faculty of Medicine, Suez Canal University, Egypt

3Department of Pathology, Faculty of Medicine, Suez Canal University, Egypt

Copyright © 2017 Samah M. Elaidy et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Globally, hepatocellular carcinoma (HCC) is the second-ranked cause of cancer-related deaths. Induction of anti-angiogenesis and apoptosis are highly effective strategies for treating HCC. Emergence of the anti-angiogenic and apoptotic properties of silver nanoparticles (AgNP) is a developing policy in cancer therapy. The present study was conducted to evaluate the therapeutic effects of polyvinylpyrrolidone (PVP)-capped AgNPs on chemically-induced HCC in rats. Induction of HCC model in male albino Wistar rats (220-250 g) was initiated by a single intraperitoneal injection of diethylnitrosamine (DEN; 200 mg/kg), then after 2 weeks promoted intraperitoneally with carbon tetrachloride (CCl4) solution (CCl4/olive oil; 1:1; 1 ml/kg) three times weekly for 6 weeks. HCC was confirmed through significant reductions in survival rates, serum albumin, elevations in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alphafetoprotein (AFP) levels and hepatic vascular endothelial growth factors (VEGF), platelet-derived growth factors (PDGF), nitric oxide (NO), interleukin (Il)-4 and -8, and tumor necrosis factor-alpha (TNF-α) levels, in addition to the histopathological dysplastic changes. PVP-AgNPs (30, 125, and 300 mg/kg/day) were given through oral gavage for 28 days. PVP-AgNPs therapy showed significant amelioration of these injurious effects with enhancement in the hepatic caspases activities, translated histopathologically to a marked improvement in the hepatic architecture. PVP-AgNPs 125mg/kg/day regimens displayed the best therapeutic effects, which considered a therapeutic modality for HCC regarding their anti-inflammatory, antiangiogenic, and caspase-dependent apoptotic effects. Advanced targeted molecular studies for use of single or combined regimens of PVP-AgNPs with different chemotherapeutics are recommended.

Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 2, pp. 9-24
doi:10.32527/2017/101422

Evaluation of the Therapeutic Effects of Polyvinylpyrrolidone-Capped Silver Nanoparticles on the Diethylnitrosamine/Carbon Tetrachloride-Induced Hepatocellular Carcinoma in Rats

Samah M. Elaidy1, Amr Moghazy2, and Mohamed K. El-Kherbetawy3

1Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Egypt

2Department of Plastic Surgery, Faculty of Medicine, Suez Canal University, Egypt

3Department of Pathology, Faculty of Medicine, Suez Canal University, Egypt

Copyright © 2017 Samah M. Elaidy et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Globally, hepatocellular carcinoma (HCC) is the second-ranked cause of cancer-related deaths. Induction of anti-angiogenesis and apoptosis are highly effective strategies for treating HCC. Emergence of the anti-angiogenic and apoptotic properties of silver nanoparticles (AgNP) is a developing policy in cancer therapy. The present study was conducted to evaluate the therapeutic effects of polyvinylpyrrolidone (PVP)-capped AgNPs on chemically-induced HCC in rats. Induction of HCC model in male albino Wistar rats (220-250 g) was initiated by a single intraperitoneal injection of diethylnitrosamine (DEN; 200 mg/kg), then after 2 weeks promoted intraperitoneally with carbon tetrachloride (CCl4) solution (CCl4/olive oil; 1:1; 1 ml/kg) three times weekly for 6 weeks. HCC was confirmed through significant reductions in survival rates, serum albumin, elevations in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alphafetoprotein (AFP) levels and hepatic vascular endothelial growth factors (VEGF), platelet-derived growth factors (PDGF), nitric oxide (NO), interleukin (Il)-4 and -8, and tumor necrosis factor-alpha (TNF-α) levels, in addition to the histopathological dysplastic changes. PVP-AgNPs (30, 125, and 300 mg/kg/day) were given through oral gavage for 28 days. PVP-AgNPs therapy showed significant amelioration of these injurious effects with enhancement in the hepatic caspases activities, translated histopathologically to a marked improvement in the hepatic architecture. PVP-AgNPs 125mg/kg/day regimens displayed the best therapeutic effects, which considered a therapeutic modality for HCC regarding their anti-inflammatory, antiangiogenic, and caspase-dependent apoptotic effects. Advanced targeted molecular studies for use of single or combined regimens of PVP-AgNPs with different chemotherapeutics are recommended.

Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 2, pp. 9-24
doi:10.32527/2017/101422

Evaluation of the Therapeutic Effects of Polyvinylpyrrolidone-Capped Silver Nanoparticles on the Diethylnitrosamine/Carbon Tetrachloride-Induced Hepatocellular Carcinoma in Rats

Samah M. Elaidy1, Amr Moghazy2, and Mohamed K. El-Kherbetawy3

1Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Egypt

2Department of Plastic Surgery, Faculty of Medicine, Suez Canal University, Egypt

3Department of Pathology, Faculty of Medicine, Suez Canal University, Egypt

Copyright © 2017 Samah M. Elaidy et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to Cite this Article

Samah M. Elaidy, Amr Moghazy, and Mohamed K. El-Kherbetawy, “Evaluation of the Therapeutic Effects of Polyvinylpyrrolidone-Capped Silver Nanoparticles on the Diethylnitrosamine/Carbon Tetrachloride-Induced Hepatocellular Carcinoma in Rats,” Egyptian Journal of Basic and Clinical Pharmacology, Vol. 7, Issue 2, pp. 9-24, 2017. doi:10.32527/2017/101422.