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1.
Cell Biochem Biophys ; 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38483755

ABSTRACT

Nucleoside analogs are a common form of chemotherapy that disrupts DNA replication and repair, leading to cell cycle arrest and apoptosis. Reactive oxygen species (ROS) production is a significant mechanism through which these drugs exert their anticancer effects. This study investigated a new nucleoside analog called FNC or Azvudine, and its impact on ROS production and cell viability in Dalton's lymphoma (DL) cells. The study found that FNC treatment resulted in a time- and dose-dependent increase in ROS levels in DL cells. After 15 and 30 min of treatment with 2 and 1 mg/ml of FNC, mitochondrial ROS production was observed in DL cells. Furthermore, prolonged exposure to FNC caused structural alterations and DNA damage in DL cells. The results suggest that FNC's ability to impair DL cell viability may be due to its induction of ROS production and indicate a need for further investigation.

2.
Asian Pac J Cancer Prev ; 24(6): 2157-2170, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37378948

ABSTRACT

OBJECTIVES: The present study aimed to provide an insight into the acute toxicity of a novel fluorinated nucleoside analogue (FNA), FNC (Azvudine or2'-deoxy-2'-ß-fluoro-4'-azidocytidine). FNC showed potent anti-viral and anti-cancer activities and approved drug for high-load HIV patients, despite, its acute toxicity study being lacking. MATERIALS AND METHODS: OECD-423 guidelines were followed during this study and the parameters were divided into four categories - behavioral parameters, physiological parameters, histopathological parameters, and supplementary tests. The behavioral parameters included feeding, body weight, belly size, organ weight and size, and mice behavior. The physiological parameters consisted of blood, liver, and kidney indicators. In histopathological parameters hematoxylin and eosin staining was performed to analyse the histological changes in the mice organs after FNC exposure. In addition, supplementary tests were conducted to assess cellular viability, DNA fragmentation and cytokine levels (IL-6 and TNF-α) in response to FNC. RESULTS: In the behavioral parameters FNC induced changes in the mice-to-mice interaction and activities. Mice's body weight, belly size, organ weight, and size remained unchanged. Physiological parameters of blood showed that FNC increased the level of WBC, RBC, Hb, and neutrophils and decreased the % count of lymphocytes. Liver enzymes SGOT (AST), and ALP was increased. In the renal function test (RFT) cholesterol level was significantly decreased. Histopathological analysis of the liver, kidney, brain, heart, lungs, and spleen showed no sign of tissue damage at the highest FNC dose of 25 mg/kg b.wt. Supplementary tests for cell viability showed no change in viability footprint, through our recently developed dilution cum-trypan (DCT) assay, and Annexin/PI. No DNA damage or apoptosis was observed in DAPI or AO/EtBr studies. Pro-inflammatory cytokines IL-6 and TNF-α increased in a dose-dependent manner. CONCLUSION: This study concluded that FNC is safe to use though higher concentration shows slight toxicity.


Subject(s)
HIV Infections , Humans , Mice , Animals , Mice, Inbred BALB C , Interleukin-6 , Tumor Necrosis Factor-alpha , Deoxycytidine , Body Weight
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