Gemcitabine induced cytotoxicity, DNA damage and hepatic injury in laboratory mice.
Waleed A Q HailanFaisal M Abou-TarboushKhalid M Al-AnaziAreeba AhmadAhmed QasemMohammed Abul FarahPublished in: Drug and chemical toxicology (2018)
The present study was conducted to demonstrate cytotoxicity, apoptosis and hepatic damage induced by gemcitabine in laboratory mice. Animals were treated with a single dose of gemcitabine (415 mg/kg body wt), equivalent to a human therapeutic dose, and sacrificed after 1, 2 and 3 weeks. A significant decrease in mean body weight and absolute liver weight was registered. The levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were increased as a result of this induced stress. Various structural changes were observed in the liver tissue of treated mice, as evident in the histological sections. Specifically, gemcitabine exposure was able to induce apoptosis in liver cells, and the incidence of TUNEL positive liver cells was increased compared to the control group. DNA fragmentation appeared on agarose gel and flow cytometry analysis confirmed the induction of apoptosis. These findings in gemcitabine-treated animal tissues suggest that inhibition or disruption of cells' DNA synthesis may be the mechanism by which this drug induces toxicity in the animal body.
Keyphrases
- cell cycle arrest
- induced apoptosis
- oxidative stress
- cell death
- endoplasmic reticulum stress
- dna damage
- pi k akt
- body weight
- diabetic rats
- locally advanced
- flow cytometry
- high fat diet induced
- high glucose
- endothelial cells
- physical activity
- gene expression
- drug induced
- radiation therapy
- dna repair
- insulin resistance
- metabolic syndrome
- electronic health record
- nucleic acid
- data analysis