Therapeutic role of a synthesized calcium phosphate nanocomposite material on hepatocarcinogenesis in rats.
Nanotechnology research is booming worldwide, and the general belief is that medical and biological applications will form the greatest sector of expansion over the next decade. With this in mind, this study was designed to evaluate the therapeutic effects of a synthesized tricalcium phosphate nanocomposite material (nano-TCP) on hepatocarcinoma in a rat model, as initiated with diethylnitrosamine (DEN) and promoted with phenobarbital (PB). Hepatocarcinoma was induced with intraperitoneal injections of DEN (50 mg·(kg body mass)(-1)) 3 times a week for 2 weeks. Three weeks after the last dose of DEN, the rats received PB (0.05 %, w/v) in their drinking water for a further 6 weeks. Nano-TCP (100 mg·(kg body mass)(-1)) was administered intraperitoneally 3 times per week to rats with HCC. At the end of the experimental period, liver samples were collected from all animals for biochemical and histopathological analysis. The degree of DNA fragmentation was analyzed, in addition to immune status, by measuring the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2). The activities of the most important free-radical scavengers of the antioxidant defense system as well as malondialdehyde (MDA) content and liver enzymes were measured. The levels of hepatic heat shock protein-70 (HSP-70), caspase-3, and metalloproteinase-9 were also measured as markers for inflammation and apoptosis. Histopathological examination of liver tissue was performed. The results revealed the potent efficacy of nano-TCP in repairing the fragmented DNA and ameliorating most of the investigated parameters by significant elevation in the levels of hepatic alanine aminotransferase (ALT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. On the other hand, there was a significant decrease in hepatic gamma-glutamyl transpeptidase (γ-GT), MDA, IL-2, IFN-γ, TNF-α, matrix metalloproteinase-9 (MMP-9), HSP-70, and caspase-3 levels upon treatment. The findings form histopathological examination of the liver tissues agreed with the biochemical results and confirmed the difference between the control and treatment groups. In conclusion, nano-TCP succeeded in treating hepatocarcinoma efficiently, and presents a new hope for patients to get safe, fast, and effective treatment.
a Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
Magdy
M
Mohammed
b Radioisotopes Department, Atomic Energy Authority, Cairo, Egypt.
Eman
E
Abdel-Gawad
c Egyptian Army forces, Cairo, Egypt.
Sameh
S
Awwad
a Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
Eman
E
Kandil
a Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
Basma
B
El-Agamy
D000818:Animals; D002130:Calcium Phosphates / Q000138:chemical synthesis / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004052:Diethylnitrosamine / Q000633:toxicity; D004798:Enzymes / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D053761:Nanocomposites / Q000737:chemistry*; D010634:Phenobarbital / Q000009:adverse effects; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014961:X-Ray Diffraction
D002130:Calcium Phosphates; D004798:Enzymes; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D004052:Diethylnitrosamine; D008315:Malondialdehyde; D007371:Interferon-gamma; C020243:calcium phosphate; D010634:Phenobarbital
hepatocarcinogenesis; hépatocarcinogenèse; nanocomposite de phosphate tricalcique; tricalcium phosphate nanocomposite