Pyrrolidine Dithiocarbamate Protects Against Cisplatin-Induced Liver Damage by Regulating NF-κB Activation


Meriç S., Arda B. P.

9th International Congress of the Molecular Biology Association of Turkey, İzmir, Türkiye, 12 - 14 Eylül 2024, ss.125, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: İzmir
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.125
  • İstanbul Üniversitesi Adresli: Evet

Özet

Background/Aim: Cisplatin is a synthetic, platinum-based chemical agent used in cancer chemo-therapy. Pyrrolidine dithiocarbamate (PDTC), known for its metalchelating properties, is a synthetic chemical compound belonging to the dithiocarbamate family, which exhibits dose-dependent antiviral, anticancer, antibacterial, antioxidant, and anti-inflammatory effects. In our study, we aimed to elucidate the effects of PDTC on cisplatin-induced liver damage in the model organism, the rat.

Materials and Method: We formed four experimental groups of 2-3 month-old 32 male Wistar albino rats. Control group animals were injected with physiological saline solution, while the second group was intraperitoneally injected with 100 mg/kg PDTC for 7 days once a day. The third and fourth experimental groups were injected with the indicated PDTC dose, along with an injection of 7 mg/kg cisplatin on the third day. After the 7 days of the experimental period, liver samples obtained from the animals were analyzed using spectrophotometry to measure aspartate aminotransferase (AST) and myeloperoxidase (MPO) activities, as well as malondialdehyde (MDA) and glutathione (GSH) levels. Additionally, phosphorylation of the NF-κB transcription factor was determined by western blotting method.

Results: This study showed that cisplatin administration results in liver damage by increasing the levels of tissue markers such as AST, MPO, and MDA, while causing a decrease in GSH. Additionally, the increase in NF-κB phosphorylation can be observed as an indicator of inflammatory activity in the cisplatin group. When compared to the cisplatin group, pre-treatment of PDTC resulted in decreased AST and MPO activities, as well as reduced MDA levels, while enhancing the levels of GSH in liver tissues. PDTC treatment also demonstrated its anti-inflammatory effect by reducing the levels of phosphorylated NF-κB.

Conclusion: In conclusion, this study shows that PDTC acts through the regulation of NF-κB acti- vation in protecting against cisplatin-induced liver damage. In addition, PDTC can be considered a chemical agent that may prevent chemotherapy-induced liver injury.