Determination of the optimal cisplatin dose to induce anemia in streptozotocin-nicotinamide-induced type 2 diabetic rats: A preliminary study.

BACKGROUND

Anemia is a major global health concern and a frequent complication of cancer chemotherapy. Patients with diabetes mellitus (DM) may experience chemotherapy-induced anemia (CIA), driven primarily by nephrotoxicity and impaired erythropoiesis. However, the interaction between pre-existing DM and CIA remains insufficiently understood, and preclinical models are limited.

AIM: To determine the optimal single-dose, acute cisplatin regimen capable of inducing moderate anemia in a streptozotocin-nicotinamide type 2 diabetic Sprague Dawley rat model.

METHODS

Twenty male Sprague Dawley rats were induced to diabetes using nicotinamide [230 mg/kg body weight (BW), i.p.] followed by streptozotocin (65 mg/kg BW, i.v.). Diabetes was confirmed 72 hours later by fasting blood glucose ≥ 150 mg/dl, with repeat measurements performed to ensure stability before cisplatin administration. Diabetic rats were randomized into four groups (n = 5 per group): control (saline) or a single IV injection of cisplatin at 4, 6, or 8 mg/kg BW. Hemoglobin (HGB), platelet (PLT), white blood cell (WBC), and neutrophil (NEU) counts were measured on days 7, 14, and 21 after injection. The optimal dose was defined as inducing >15% HGB reduction without mortality.

RESULTS

Cisplatin induced a significant dose-dependent reduction in HGB. The 4 mg/kg BW group developed mild anemia, whereas the 6 and 8 mg/kg BW doses produced moderate anemia (>15% HGB reduction) beginning on day 14 and maintained it through day 21 (≈20.8%-21.1%). All treated groups showed significant thrombocytopenia (decreased PLT count), leukocytosis (increased WBC count), and absolute neutrophilia (increased NEU count with increased WBC count). Weight loss (15.1%-16.2%) occurred across the groups, with the 6-mg/kg BW cohort exhibiting a less severe reduction than the 8-mg/kg BW group. No mortality occurred in any of the groups.

CONCLUSION

A single dose of cisplatin (6 mg/kg BW) induces moderate, non-lethal CIA in diabetic Sprague Dawley rats while preserving tolerability. This preliminary study provides foundational dose-response data for developing diabetic-specific CIA models. However, additional validation incorporating comprehensive hematological and mechanistic assessments is required.