Early Dose-Related Cardiorenal Effects of Cisplatin: Integrated Biochemical, Molecular and Histopathological Evaluation in an Experimental Rat Model

Q: What are the key findings of this study?

Cisplatin induced significant dose-dependent increases in cardiorenal injury markers and cardiac Bax in rats at 3 days.

Q: What is the clinical evidence from this study?

Population: Cisplatin-induced acute cardiorenal toxicity (experimental rat model) (n=38). Intervention: Cisplatin vs. Single intraperitoneal dose of 1 mL 0.9% isotonic saline. Primary outcome: Early dose-dependent cardiorenal toxicity markers (serological Troponin T, CK-MB, urea, creatinine; tissue MDA, LPO, SOD; Bax/Bcl-2 protein expression; histopathology) (p=<0.001).

Q: What does this research mean for the field?

Acute cisplatin exposure produces dose-dependent cardiorenal toxicity in rats characterized by increases in tissue injury markers, pro-apoptotic signaling, and oxidative stress rather than prominent cytokine-mediated inflammation. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the early dose-dependent toxic effects of cisplatin on cardiac and renal tissues at biochemical, molecular, and histopathological levels.

Gülsüm Abuşoğlu; Melek Altunkaya; Mehmet Burak Ateş; Ayşegül Bulut; Bahadır Öztürk

doi:10.3390/biomedicines14071490

June 30, 2026BiomedicinesOpen Access

Early Dose-Related Cardiorenal Effects of Cisplatin: Integrated Biochemical, Molecular and Histopathological Evaluation in an Experimental Rat Model

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Key result

Cisplatin induces dose-dependent cardiorenal injury markers with up to ~2.8-fold higher cardiac Bax in rats.

P<0.001
n=38

Figures

Why the study?

Cisplatin is widely used in chemotherapy, but its dose-dependent effects on different tissues are not fully understood.

Does acute cisplatin administration induce dose-dependent biochemical, molecular, and histopathological cardiorenal toxicity in a male Wistar rat model?

Key Points

To evaluate the early dose-dependent toxic effects of cisplatin on cardiac and renal tissues at biochemical, molecular, and histopathological levels.
Male Wistar albino rats were divided into four groups: control, 5 mg/kg, 7.5 mg/kg, and 12 mg/kg cisplatin.
Kidney and heart tissues were harvested 3 days post-administration to analyze oxidative stress markers (ELISA), apoptotic proteins (Western blot and immunohistochemistry), and histopathology.
Renal markers urea and creatinine increased significantly at 7.5 mg/kg (P < 0.001 and P = 0.002) and 12 mg/kg (both P < 0.001), while cardiac troponin T and CK-MB also rose significantly with increasing doses (both P < 0.001).
Across kidney and heart tissues, MDA (P = 0.03) and LPO (P < 0.001) increased while SOD decreased (P = 0.042); TNF-α rose only at 12 mg/kg (P = 0.04), whereas IL-6 (P = 0.296), IL-10 (P = 0.167), and IL-1β (P = 0.278) lacked clear dose-dependent patterns.
At 12 mg/kg, Bax protein expression rose 8.6-fold in kidneys (P = 0.027) and 2.8-fold in hearts (P = 0.017), while Bcl-2 fell by 80% (P = 0.002) and 79% (P = 0.022), respectively.

Structured PICO

Does acute cisplatin administration induce dose-dependent biochemical, molecular, and histopathological cardiorenal toxicity in a male Wistar rat model?

P

Population

38 male Wistar albino rats (8–12 weeks old) allocated to control or escalating single doses of intraperitoneal cisplatin and followed for 3 days.

I

Intervention

Cisplatin administered as a single intraperitoneal dose of 5 mg/kg (n=10), 7.5 mg/kg (n=10), or 12 mg/kg (n=10)

C

Comparator

Single intraperitoneal dose of 1 mL 0.9% isotonic saline (n=8)

O

Outcome

Early dose-related cardiorenal toxicity at 3 days after administration, evaluated via biochemical markers (plasma urea, creatinine, CK-MB, Troponin T), oxidative stress and inflammatory markers (ELISA for MDA, LPO, SOD, 4-HNE, IL-6, IL-10, IL-1β, TNF-α), apoptotic proteins (Western blot and immunohistochemistry for Bax and Bcl-2), and histopathological semi-quantitative scoringsurrogate

Main Result

p-value: p=<0.001

In an acute rat model, cisplatin exposure induced dose-dependent cardiorenal toxicity characterized primarily by oxidative stress, mitochondrial apoptotic signaling (Bax/Bcl-2), and histopathological injury within 3 days, with more pronounced damage at doses of 7.5 and 12 mg/kg.

Limitations

Relatively small sample size (n=38 rats total)
Acute single-dose cisplatin administration model with a single 3-day post-treatment time point, precluding conclusions on chronic or cumulative toxicity
Absence of temporal multi-point kinetic analyses
Lack of highly sensitive early renal injury biomarkers such as KIM-1 and NGAL
Absence of caspase pathway analyses and fluorescent apoptosis staining methods (Calcein AM, ethidium homodimer, or Hoechst staining)
Acute 3-day observation period
Formalin fixation and paraffin embedding may contribute to epitope masking in cardiac tissue, potentially reducing immunohistochemical sensitivity

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Implication

Highlights early cardiorenal injury in cisplatin-treated rats; hypothesis-generating for mechanisms but should not change clinical practice.

Abstract

Background/Objectives: Cisplatin (CP) is a widely used chemotherapeutic agent; however, its dose-dependent effects on different tissues are not fully understood. This study aimed to investigate the early dose-related cardiorenal toxicity of CP at biochemical, molecular, and histopathological levels. Methods: Male Wistar albino rats were divided into four groups: Control, 5 mg/kg CP, 7.5 mg/kg CP, and 12 mg/kg CP. Cardiac and renal tissues were collected three days after administration. Oxidative stress and inflammatory parameters were analyzed using ELISA. Histopathological evaluation and semi-quantitative scoring were performed on tissue sections. Apoptosis-related proteins were assessed using Western blotting and immunohistochemistry. Results: In both renal and cardiac tissues, LPO, MDA, and SOD levels showed significant dose-dependent changes, whereas inflammatory parameters did not differ significantly among the groups. Although Bax and Bcl-2 proteins displayed significant dose-dependent variations in both tissues at the protein level, immunohistochemical analyses showed no notable differences in cardiac tissue. Conclusions: Acute cisplatin exposure produced dose-related biochemical, molecular, and histopathological alterations in both cardiac and renal tissues. Oxidative stress-related changes were more prominent than cytokine-mediated inflammatory responses during the acute experimental period. Within the conditions of this acute model, lower cisplatin doses were associated with less pronounced tissue alterations.

Discussion

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Cite This Study

Abuşoğlu et al. (2026) studied Cisplatin-induced acute cardiorenal toxicity (experimental rat model) (n=38). Cisplatin vs. Single intraperitoneal dose of 1 mL 0.9% isotonic saline was evaluated on Early dose-dependent cardiorenal toxicity markers (serological Troponin T, CK-MB, urea, creatinine; tissue MDA, LPO, SOD; Bax/Bcl-2 protein expression; histopathology) (p=<0.001). Cisplatin induced significant dose-dependent increases in cardiorenal injury markers and cardiac Bax in rats at 3 days.

synapsesocial.com/papers/6a4600209ed13430313104d0 https://doi.org/10.3390/biomedicines14071490

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Early Dose-Related Cardiorenal Effects of Cisplatin: Integrated Biochemical, Molecular and Histopathological Evaluation in an Experimental Rat Model

Figures

Key Points

Structured PICO

Main Result

Limitations

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Implication

Abstract

Discussion

Cite This Study

Early Dose-Related Cardiorenal Effects of Cisplatin: Integrated Biochemical, Molecular and Histopathological Evaluation in an Experimental Rat Model

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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