TY - JOUR
T1 - Safety Assessment of a Nucleoside Analogue FNC (2’-deoxy-2’-β-fluoro-4’-azidocytidine ) in Balb/c Mice
T2 - Acute Toxicity Study
AU - Kumar, Naveen
AU - Delu, Vikram
AU - Shukla, Alok
AU - Singh, Rishi Kant
AU - Ulasov, Ilya
AU - Fayzullina, Daria
AU - Kumar, Sandeep
AU - Patel, Anand Kumar
AU - Yadav, Lokesh
AU - Tiwari, Ruchi
AU - Rachana, Kumari
AU - Mohanta, Shivashish Priyadarshi
AU - Kumar, Sanjay
AU - Kaushalendra, Kaushalendra
AU - Acharya, Arbind
N1 - Publisher Copyright:
© This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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’-β-fluoro-4’-azidocytidine). FNC showed potent anti-viral and anticancer 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.
AB - 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’-β-fluoro-4’-azidocytidine). FNC showed potent anti-viral and anticancer 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.
KW - Azvudine
KW - antiviral agents
KW - kidney
KW - organization for economic co-operation and development
UR - http://www.scopus.com/inward/record.url?scp=85163597224&partnerID=8YFLogxK
U2 - 10.31557/APJCP.2023.24.6.2157
DO - 10.31557/APJCP.2023.24.6.2157
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C2 - 37378948
AN - SCOPUS:85163597224
SN - 1513-7368
VL - 24
SP - 2157
EP - 2170
JO - Asian Pacific Journal of Cancer Prevention
JF - Asian Pacific Journal of Cancer Prevention
IS - 6
ER -
