Investigation of the effects of Theranekron and Sorafenib treatments on carcinogenesis, apoptosis and biochemical profile in hepatocellular carcinoma in rats


Vanli S., Kurtoglu F., Alan B. S., AKÇAKAVAK G., Ozdemir O.

Toxicology Mechanisms and Methods, cilt.34, sa.7, ss.750-760, 2024 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 34 Sayı: 7
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1080/15376516.2024.2332909
  • Dergi Adı: Toxicology Mechanisms and Methods
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Environment Index, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.750-760
  • Anahtar Kelimeler: caspase-10, Caspase-3, Granzyme-B, hepatocellular carcinoma, Sorafenib, Theranekron
  • Yozgat Bozok Üniversitesi Adresli: Evet

Özet

This study aimed to investigate the effects of Tarantula cubensis alcohol extract (TCAE, Theranekron) and Sorafenib (S) treatments on carcinogenesis, apoptosis and biochemical profile of rats with experimentally induced hepatocellular carcinoma (HCC). In the presented study, 58 male rats were divided into 7 groups; Negative Control (NC, n = 6), NC + TCAE (NCT, n = 6), NC + Sorafenib (NCS, n = 6), Positive Control (PC, n = 10), Positive Control + TCAE (PCT, n = 10), Positive Control + Sorafenib (PCS, n = 10), Positive Control + TCAE + Sorafenib (PCTS, n = 10). The active ingredients Diethylnitrosamine (DEN, 120 mg/kg, single dose) and Nitrosomorpholine (NMOR, 50 ppm, 21 weeks orally) were used to induce HCC in rats. At the end of the experiment, the animals were euthanized under appropriate conditions and samples were collected for biochemical and pathological investigations. In the PC group, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) levels were higher (p < 0.001) and urea levels were lower (p < 0.001) compared to all other groups. Treatment groups reorganized the relevant markers (ALT, AST, GGT, and urea). A significant increase was detected in Caspase-10, Caspase-3 and Granzyme-B (GrzB) (p < 0.001) in blood and Caspase-10 and GrzB (p < 0.05) in liver tissue in PCT, PCS and PCTS groups compared to the PC group. Histopathological examination revealed that the PC group showed cancer morphology, and the treatment groups caused a decrease in tumor incidence and size. Our current findings suggest that the mechanism of action of TCAE in HCC is through the NKs/CTLs-GrzB-Casp10-Casp3 signaling pathway and can be used in combination with chemotherapy drugs for the development of future drug designs.