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Research Article


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

Agus Jati Sunggoro, Paramasari Dirgahayu, Bambang Purwanto, Eti Poncorini Pamungkasari, Brian Warsita, Risya Cilmiaty, Damiana Tribhuwaneswari Mahendra Wardhani, Yohanna Handika Putri Kusuma Dewi.


Abstract
Background:
Anemia is a major global health concern and a frequent complication of cancer chemotherapy. Patients with diabetes mellitus (DM) may experience cisplatin-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 (STZ–NA) type 2 diabetic Sprague Dawley rat model.

Methods:
Twenty male Sprague Dawley rats were induced diabetic using nicotinamide (230 mg/kg BW, i.p.) followed by streptozotocin (65 mg/kg BW, i.v.). Diabetes was confirmed 72 h later by fasting blood glucose (FBG) ≥ 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 body weight) 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.

Key words: Erythropoietic suppression; Myelosuppression; Platinum compound toxicity; Preclinical anemia model; STZ-nicotinamide rat model.


 
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How to Cite this Article
Pubmed Style

Sunggoro AJ, Dirgahayu P, Purwanto B, Pamungkasari EP, Warsita B, Cilmiaty R, Wardhani DTM, Dewi YHPK. Determination of the optimal cisplatin dose to induce anemia in streptozotocin-nicotinamide-induced type 2 diabetic rats: A preliminary study. Open Vet. J.. 2026; 16(2): 1090-1111. doi:10.5455/OVJ.2026.v16.i2.29


Web Style

Sunggoro AJ, Dirgahayu P, Purwanto B, Pamungkasari EP, Warsita B, Cilmiaty R, Wardhani DTM, Dewi YHPK. Determination of the optimal cisplatin dose to induce anemia in streptozotocin-nicotinamide-induced type 2 diabetic rats: A preliminary study. https://www.openveterinaryjournal.com/?mno=285025 [Access: February 27, 2026]. doi:10.5455/OVJ.2026.v16.i2.29


AMA (American Medical Association) Style

Sunggoro AJ, Dirgahayu P, Purwanto B, Pamungkasari EP, Warsita B, Cilmiaty R, Wardhani DTM, Dewi YHPK. Determination of the optimal cisplatin dose to induce anemia in streptozotocin-nicotinamide-induced type 2 diabetic rats: A preliminary study. Open Vet. J.. 2026; 16(2): 1090-1111. doi:10.5455/OVJ.2026.v16.i2.29



Vancouver/ICMJE Style

Sunggoro AJ, Dirgahayu P, Purwanto B, Pamungkasari EP, Warsita B, Cilmiaty R, Wardhani DTM, Dewi YHPK. Determination of the optimal cisplatin dose to induce anemia in streptozotocin-nicotinamide-induced type 2 diabetic rats: A preliminary study. Open Vet. J.. (2026), [cited February 27, 2026]; 16(2): 1090-1111. doi:10.5455/OVJ.2026.v16.i2.29



Harvard Style

Sunggoro, A. J., Dirgahayu, . P., Purwanto, . B., Pamungkasari, . E. P., Warsita, . B., Cilmiaty, . R., Wardhani, . D. T. M. & Dewi, . Y. H. P. K. (2026) Determination of the optimal cisplatin dose to induce anemia in streptozotocin-nicotinamide-induced type 2 diabetic rats: A preliminary study. Open Vet. J., 16 (2), 1090-1111. doi:10.5455/OVJ.2026.v16.i2.29



Turabian Style

Sunggoro, Agus Jati, Paramasari Dirgahayu, Bambang Purwanto, Eti Poncorini Pamungkasari, Brian Warsita, Risya Cilmiaty, Damiana Tribhuwaneswari Mahendra Wardhani, and Yohanna Handika Putri Kusuma Dewi. 2026. Determination of the optimal cisplatin dose to induce anemia in streptozotocin-nicotinamide-induced type 2 diabetic rats: A preliminary study. Open Veterinary Journal, 16 (2), 1090-1111. doi:10.5455/OVJ.2026.v16.i2.29



Chicago Style

Sunggoro, Agus Jati, Paramasari Dirgahayu, Bambang Purwanto, Eti Poncorini Pamungkasari, Brian Warsita, Risya Cilmiaty, Damiana Tribhuwaneswari Mahendra Wardhani, and Yohanna Handika Putri Kusuma Dewi. "Determination of the optimal cisplatin dose to induce anemia in streptozotocin-nicotinamide-induced type 2 diabetic rats: A preliminary study." Open Veterinary Journal 16 (2026), 1090-1111. doi:10.5455/OVJ.2026.v16.i2.29



MLA (The Modern Language Association) Style

Sunggoro, Agus Jati, Paramasari Dirgahayu, Bambang Purwanto, Eti Poncorini Pamungkasari, Brian Warsita, Risya Cilmiaty, Damiana Tribhuwaneswari Mahendra Wardhani, and Yohanna Handika Putri Kusuma Dewi. "Determination of the optimal cisplatin dose to induce anemia in streptozotocin-nicotinamide-induced type 2 diabetic rats: A preliminary study." Open Veterinary Journal 16.2 (2026), 1090-1111. Print. doi:10.5455/OVJ.2026.v16.i2.29



APA (American Psychological Association) Style

Sunggoro, A. J., Dirgahayu, . P., Purwanto, . B., Pamungkasari, . E. P., Warsita, . B., Cilmiaty, . R., Wardhani, . D. T. M. & Dewi, . Y. H. P. K. (2026) Determination of the optimal cisplatin dose to induce anemia in streptozotocin-nicotinamide-induced type 2 diabetic rats: A preliminary study. Open Veterinary Journal, 16 (2), 1090-1111. doi:10.5455/OVJ.2026.v16.i2.29