Dose-Response Assessment of Semaglutide: High-Dose-Induced Hepatotoxicity in Male Albino Rats

Abstract

The objective of this research was to assess the effect of oral semaglutide at doses (low, moderate, and high) on the hepatic enzymes, oxidative stress markers, antioxidants, and histological of the liver in Swiss-albino rats. A total of 40 adult male albino rats were randomly divided equally into four groups. G1 was the control group, and it was given distilled water. G2, G3, and G4 was administered (0.74, 1.67, 3.27 mg/kg) of semaglutide. The substances were given orally using a dosing tube once a day for 30 days. The levels liver enzymes ALT, AST, and ALP, oxidative stress MDA, and antioxidants SOD and GSH, were estimated. The liver was removed for histological examination. The results were shown not statistically significant for liver enzyme levels in G2 and G3 compared to (G1), a significant increase in antioxidants and a significant decrease in MDA were also recorded in G3, and without pathological changes appearing in the liver tissue. While, G4 showed significant increase in liver enzymes and MDA, along with a significant decrease in the level of antioxidant compared to (G1). significant pathological changes, including cellular necrosis, cellular injury, sinusoidal dilation, central venous congestion, hemorrhage, lymphocytic infiltration, and changes in the bile ducts. The low and medium doses showed improvement in biochemical indicators, while the high dose showed hepatotoxicity