pazopanib and Fatty-Liver

Pazopanib is an effective treatment for advanced renal cell carcinoma and soft tissue sarcoma. Besides classical adverse events of this drug class, hepatotoxicity has been described as a frequent side effect. The aim of the present study was to evaluate the effect of pazopanib on the liver in an experimental rat model. Sixteen Wistar albino rats were divided into 3 groups: experimental toxicity was induced with pazopanib (10 mg/kg) administered for 28 days (group 2) or 56 days (group 3) orally by gavage. Group 1 (control group) received only distilled water. Rats in groups 2 and 3 were sacrificed after the collection of blood and tissue samples on the 28th and 56th days, respectively. We found significant differences in bilirubin, alkaline phosphatase, lactate dehydrogenase, glucose, triglyceride, very-low-density lipoprotein, and iron values (p < 0.050 for all) but none in any other parameter (p > 0.050). All rats in the control group had normal histological features; however, none of the rats in groups 2 and 3 showed normal histology. In group 2, we observed mild sinusoidal dilatation, congestion, enlarged Kupffer cells, accumulation of yellow-brown-black pigment in the Kupffer cells and the accumulation of hemosiderin with Prussian blue reaction in the hepatocytes. In group 3, the findings mentioned above were more prominent, and besides these findings focal acinar transformation and macrovesicular steatosis were also observed. In group 3, mild inflammation within the portal areas was observed consisting of lymphocytes, neutrophils, and eosinophils. This study is the first that reports the biochemical and histopathological evaluation of pazopanib-related hepatic toxicity.

Topics: Administration, Oral; Alkaline Phosphatase; Animals; Bilirubin; Blood Chemical Analysis; Blood Glucose; Chemical and Drug Induced Liver Injury; Fatty Liver; Hemosiderin; Indazoles; Kupffer Cells; Liver; Male; Pyrimidines; Rats; Rats, Wistar; Sulfonamides

Novel drugs targeting molecular pathways involved in tumor development have revolutionized cancer treatment. Radiologists often focus on therapeutic response when evaluating cancer patients and may miss important signs of drug toxicity. This article familiarizes radiologists with the complications of molecular targeted agents in abdominal solid organs, enabling early identification and appropriate intervention and thus reducing patient morbidity and mortality.. Knowledge of the common abdominal toxicities--including hepatitis, cholecystitis, pancreatitis, fluid retention, and infection--is crucial for early diagnosis, which may spare patients devastating complications or the need for surgery.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Bevacizumab; Chemical and Drug Induced Liver Injury; Cholecystitis; Early Diagnosis; Edema; Fatty Liver; Female; Health Knowledge, Attitudes, Practice; Humans; Indazoles; Infections; Male; Middle Aged; Molecular Targeted Therapy; Neoplasms; Pancreatitis; Protein-Tyrosine Kinases; Pyrimidines; Radiography, Abdominal; Sulfonamides; Vascular Endothelial Growth Factor A; Young Adult