Lack of reproducible, dose-related effects of rHuEpo or DA on viability and apoptosis of nonhematopoietic cells after exposure to cytotoxic insults
| Cardiac myocytes | H2O2 | 8 studies (rHuEpo tested in 8: DA tested in 6) |
| 2 of 8: no improved viability at all ESA doses | ||
| 6 of 8: modest increase in viability in some groups | ||
| No dose-related effect observed, variable effects within each ESA, variable effects between ESAs | ||
| Hypoxia (< 1.5% O2) | 3 studies (rHuEpo and DA tested in each) | |
| 3 of 3: rHuEpo modestly increased viability | ||
| 2 of 3: DA modestly increased viability | ||
| No dose-related effect observed with ESAs (n = 1) | ||
| Staurosporine | 6 studies (rHuEpo and DA tested in each) | |
| 2 of 6: ESAs did not increase viability/reduce apoptosis | ||
| 3 of 6: ESAs modestly reduced apoptosis in some groups | ||
| No dose-related effect observed | ||
| 1 of 6: wide dose range (rHuEpo, 0.2-20 U/mL; DA, 1-100 ng/mL) | ||
| rHuEpo modestly reduced apoptosis at highest dose (20 U/mL) | ||
| No effect with DA | ||
| Renal proximal tubule cells | Cisplatin (10-20μM) | 16 studies (DA tested) |
| 16 of 16: no consistent dose-related increase in viability/reduction in apoptosis with DA | ||
| 5 of 16: 0.15-1500 ng/mL, 3-24 hours before cisplatin, apoptosis at 48-72 hours after cisplatin measured | ||
| 9 of 16: 0.15-1500 ng/mL, 3-24 hours before cisplatin, viability at 48-72 hours after cisplatin measured | ||
| 1 of 16: 1.5-150 ng/mL and cisplatin added simultaneously, apoptosis measured at 48 hours | ||
| 1 of 16: 1.5-150 ng/mL and cisplatin added simultaneously, viability measured at 48 hours | ||
| Neuronal cell line (SH-SY5Y) | Hypoxia (< 1.5% O2) | 15 studies |
| 15 of 15: no improvement in cell viability was observed with rHuEpo | ||
| 6 of 15: 24 hours of hypoxia | ||
| 6 of 15: 24 hours of hypoxia in the absence of glucose | ||
| 3 of 15: 5-6 hours of hypoxia in the absence of glucose plus 20 hours of normoxia | ||
| Neuronal cell line (PC-12) | Hypoxia (< 1.5% O2) | 8 studies |
| 8 of 8: no improvement in cell viability was observed with rHuEpo | ||
| 3 of 8: 24 hours of hypoxia | ||
| 3 of 8: 24 hours of hypoxia in the absence of glucose | ||
| 2 of 8: 5 hours of hypoxia in the absence of glucose plus 20 hours of normoxia |
| Cardiac myocytes | H2O2 | 8 studies (rHuEpo tested in 8: DA tested in 6) |
| 2 of 8: no improved viability at all ESA doses | ||
| 6 of 8: modest increase in viability in some groups | ||
| No dose-related effect observed, variable effects within each ESA, variable effects between ESAs | ||
| Hypoxia (< 1.5% O2) | 3 studies (rHuEpo and DA tested in each) | |
| 3 of 3: rHuEpo modestly increased viability | ||
| 2 of 3: DA modestly increased viability | ||
| No dose-related effect observed with ESAs (n = 1) | ||
| Staurosporine | 6 studies (rHuEpo and DA tested in each) | |
| 2 of 6: ESAs did not increase viability/reduce apoptosis | ||
| 3 of 6: ESAs modestly reduced apoptosis in some groups | ||
| No dose-related effect observed | ||
| 1 of 6: wide dose range (rHuEpo, 0.2-20 U/mL; DA, 1-100 ng/mL) | ||
| rHuEpo modestly reduced apoptosis at highest dose (20 U/mL) | ||
| No effect with DA | ||
| Renal proximal tubule cells | Cisplatin (10-20μM) | 16 studies (DA tested) |
| 16 of 16: no consistent dose-related increase in viability/reduction in apoptosis with DA | ||
| 5 of 16: 0.15-1500 ng/mL, 3-24 hours before cisplatin, apoptosis at 48-72 hours after cisplatin measured | ||
| 9 of 16: 0.15-1500 ng/mL, 3-24 hours before cisplatin, viability at 48-72 hours after cisplatin measured | ||
| 1 of 16: 1.5-150 ng/mL and cisplatin added simultaneously, apoptosis measured at 48 hours | ||
| 1 of 16: 1.5-150 ng/mL and cisplatin added simultaneously, viability measured at 48 hours | ||
| Neuronal cell line (SH-SY5Y) | Hypoxia (< 1.5% O2) | 15 studies |
| 15 of 15: no improvement in cell viability was observed with rHuEpo | ||
| 6 of 15: 24 hours of hypoxia | ||
| 6 of 15: 24 hours of hypoxia in the absence of glucose | ||
| 3 of 15: 5-6 hours of hypoxia in the absence of glucose plus 20 hours of normoxia | ||
| Neuronal cell line (PC-12) | Hypoxia (< 1.5% O2) | 8 studies |
| 8 of 8: no improvement in cell viability was observed with rHuEpo | ||
| 3 of 8: 24 hours of hypoxia | ||
| 3 of 8: 24 hours of hypoxia in the absence of glucose | ||
| 2 of 8: 5 hours of hypoxia in the absence of glucose plus 20 hours of normoxia |
DA indicates darbepoetin alfa; and ESAs, erythropoiesis-stimulating agents.