Related Experiment Videos
Toxicologic evaluation of streptozotocin (NSC 85998) in mice, dogs and monkeys
Abstract:
Single intravenous doses of CDF1 mice, and single and five daily intravenous treatment schedules in beagle dogs and rhesus monkeys were used to evaluate the toxicity of Streptozotocin (SZN). The major target organs in the three species were liver, kidney, lymphoid tissue and pancreatic islet beta cells. Moderate bone marrow depression and gastrointestinal toxicity were observed in the large animal species after lethal doses. Monkeys were less sensitive than the dog to the hepatotoxic effects of SZN and clinical signs of liver dysfunction were more severe in dogs after multiple doses. Microscopic lesions in the renal proximal convoluted tubules were present in the three species; these lesions appeared to be irreversible for dogs. The toxic effect on the endocrine pancreas was manifest by hyperglycemia, glucosuria, islet atrophy and beta cell degranulation. Multiple dose regimens were less toxic than single doses in dogs and monkeys in terms of the total dose received.
Insights
Streptozotocin (SZN) toxicity primarily affects the liver, kidney, lymphoid tissue, and pancreatic islet beta cells in mice, dogs, and monkeys. Multiple doses were less toxic than single doses in dogs and monkeys.
Area of Science:
- Toxicology
- Pharmacology
- Comparative Pathology
Background:
- Streptozotocin (SZN) is a compound with known cytotoxic properties.
- Understanding its toxicity profile across different species is crucial for risk assessment.
Purpose of the Study:
- To evaluate the toxicity of Streptozotocin (SZN) in CDF1 mice, beagle dogs, and rhesus monkeys.
- To identify target organs and assess species-specific responses to SZN treatment.
Main Methods:
- Administered single intravenous doses of SZN to mice.
- Utilized single and five daily intravenous treatment schedules in dogs and monkeys.
- Monitored clinical signs, performed necropsies, and conducted histopathological examinations.
Main Results:
- Major target organs included the liver, kidney, lymphoid tissue, and pancreatic islet beta cells across all species.
- Renal proximal convoluted tubule lesions were observed in all species and appeared irreversible in dogs.
- Hepatotoxicity was more pronounced in dogs, especially after multiple doses, while monkeys showed less sensitivity.
- Endocrine pancreas toxicity manifested as hyperglycemia, glucosuria, islet atrophy, and beta cell degranulation.
Conclusions:
- SZN exhibits significant toxicity in the liver, kidneys, lymphoid tissues, and pancreas.
- Species differences exist in SZN-induced hepatotoxicity, with dogs being more susceptible.
- Renal and pancreatic toxicity may be irreversible, highlighting the need for careful dosing and monitoring.