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Doxorubicin treatment of rabbit renal VX-2 carcinoma: nephrotoxicity, serum parameters and weight
G Gadeholt-Göthlin1, H Vik, J H Göthlin
1Department of Radiology, Göteborg University, Sahlgrenska Hospital, Sweden.
Abstract:
Serum electrolytes, creatinine, urea, protein, albumin, bilirubin and glucose were examined every 4 days until time of death in rabbits with VX-2 carcinoma implanted in one kidney. The rabbits were treated with doxorubicin, nephrectomy or combinations thereof and observed for up to 1 year. Rabbits treated with doxorubicin only showed a slight creatinine rise initially, but over time creatinine reached almost the same concentration as that in nephrectomized rabbits receiving equivalent doses of doxorubicin. Creatinine concentrations increased significantly above the normal range following nephrectomy combined with doxorubicin. Doxorubicin nephrotoxicity in rabbits occurs at lower doses than previously reported. In all rabbits the parameters except creatinine remained stable within the established normal ranges, except for the last 4 days before time of death in the animals with metastatic disease. Weight loss was the best parameter for making a prognosis for an individual rabbit, since peak weight was noted 16-20 days before death. In experimental work with VX-2 carcinoma, weight is thus the most important indicator of the time at which rabbits not responding to treatment can be put to death to avoid unnecessary suffering before the end of the experiment.
Insights
This study shows doxorubicin causes kidney damage (nephrotoxicity) in rabbits, especially when combined with kidney removal (nephrectomy). Weight loss is a key indicator for prognosis in VX-2 carcinoma models.
Area of Science:
- Nephrology
- Oncology
- Pharmacology
Background:
- VX-2 carcinoma is a common model for kidney cancer research.
- Doxorubicin is a widely used chemotherapy agent with known nephrotoxic potential.
- Assessing drug toxicity and establishing humane endpoints are critical in animal research.
Purpose of the Study:
- To evaluate the nephrotoxicity of doxorubicin in rabbits with VX-2 kidney carcinoma.
- To determine the impact of nephrectomy on doxorubicin-induced kidney damage.
- To identify reliable indicators for prognosis and humane endpoints in this experimental model.
Main Methods:
- Rabbits with VX-2 carcinoma underwent treatments including doxorubicin, nephrectomy, or combination therapy.
- Serum electrolytes, creatinine, urea, protein, albumin, bilirubin, and glucose were monitored every 4 days.
- Body weight was tracked throughout the observation period (up to 1 year).
Main Results:
- Doxorubicin alone caused a slight initial rise in creatinine, which later matched levels seen in nephrectomized rabbits receiving equivalent doses.
- Combined nephrectomy and doxorubicin treatment led to significant increases in creatinine above normal ranges.
- Doxorubicin nephrotoxicity was observed at lower doses than previously reported.
- Other serum parameters remained stable except in the final 4 days before death in rabbits with metastatic disease.
- Weight loss was the most accurate predictor of prognosis, with peak weight occurring 16-20 days before death.
Conclusions:
- Doxorubicin exhibits significant nephrotoxicity in rabbits, potentiated by nephrectomy.
- The study suggests lower effective doses for doxorubicin-induced nephrotoxicity than previously established.
- Monitoring weight loss is crucial for determining humane endpoints in VX-2 carcinoma rabbit models.
- Serum creatinine is a sensitive indicator of doxorubicin nephrotoxicity in this model.