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Renal functional teratogenesis resulting from adriamycin exposure
Insights
Adriamycin exposure during pregnancy can harm fetal kidney development. Later gestational exposure (days 10-12) showed more significant impacts on offspring renal function compared to earlier exposure.
Area of Science:
- Toxicology
- Developmental Biology
- Nephrology
Background:
- Adriamycin (doxorubicin) is a chemotherapy agent with known teratogenic potential.
- Prenatal exposure to nephrotoxic agents can lead to long-term renal dysfunction.
- Understanding the specific timing and dose-dependent effects of adriamycin on fetal kidney development is crucial.
Purpose of the Study:
- To investigate the impact of adriamycin exposure during specific gestational periods on the renal functional competence of offspring rats.
- To evaluate the dose-response relationship and critical developmental windows for adriamycin-induced nephrotoxicity.
- To assess various parameters of renal function, including clearance, concentration, dilution, and acid excretion.
Main Methods:
- Pregnant Sprague-Dawley rats were administered adriamycin (0, 1.0, or 1.5 mg/kg/day) via intraperitoneal injection on gestational days 7-10 or 10-12.
- Offspring were assessed for growth, viability, and a comprehensive panel of renal function tests.
- Renal function tests included serum concentrations, clearances, urine concentrating/diluting ability, and acid excretion capacity.
Main Results:
- Exposure during gestational days 7-10 resulted in more overt developmental toxicity.
- Exposure during gestational days 10-12, particularly at higher doses, led to more pronounced alterations in offspring renal function.
- Renal function tests confirmed the nature and magnitude of adriamycin's effects on kidney development.
Conclusions:
- The timing of adriamycin exposure during gestation significantly influences the type and severity of toxicity observed in offspring.
- Gestational days 10-12 represent a more sensitive period for adriamycin-induced renal functional impairment.
- A combination of basal clearance and renal concentrating tests is recommended for detecting prenatal kidney alterations.
Abstract:
Pregnant Sprague-Dawley rats were exposed to adriamycin and offspring were evaluated for renal functional competence. Exposure consisted of 0, 1.0 or 1.5 mg/kg/day by intraperitoneal injection on either gestational days 7-10 or 10-12. The exposed offspring were evaluated for 1) growth and viability; 2) serum concentrations and renal clearances of creatinine, urea, glucose, sodium, potassium, chloride, and total osmotic particles; 3) the ability to excrete an osmotically concentrated urine following fluid deprivation; 4) the ability to excrete an osmotically dilute urine following isotonic volume expansion; and 5) the ability to secrete hydrogen ions following administration of a fixed acid. Exposure during days 7-10 of gestation produced greater evidence of overt developmental toxicity than did exposure during days 10-12 of gestation. The reverse was true, however, for the effects of adriamycin on renal function, as the majority of effects on these measures were found in the high-dose pups exposed during days 10-12 of gestation. The application of the renal function tests did not lower the observed effect level for adriamycin-induced developmental toxicity, but it did provide confirmatory information on the nature of the effect, on the magnitude of the effect in the exposed population, and on the possible morphological site of observed functional lesion. For reasons discussed in the text, a combination of the basal clearance test and the renal concentrating test appears to provide the most efficient means for detecting the presence of prenatally induced functional alterations of the kidneys.