Objective:

2

To investigate cisplatin-induced cardiovascular toxicity and explore the protective effects and potential mechanism of curcumin co-treatment.

Methods:

2

Forty adult male Sprague-Dawley rats were numbered and randomly divided into control group

cisplatin group (7.5 mg/kg

once a week

for 2 weeks)

curcumin group (200 mg/kg per day

for 2 weeks) and cisplatin+curcumin group (cisplatin 7.5 mg/kg

once a week

and curcumin 200 mg/kg per day for 2 weeks) by a random number table method

with 10 rats in each group. Cardiac and vascular morphology and functions were assessed using hematoxylin-eosin and Masson's trichrome staining

serum indexes detection

echocardiography

electrocardiogram (ECG)

blood pressure monitoring

vascular ring isometric tension measurement

and left ventricular pressure evaluation. The expressions of extracellular signal-regulated kinases (ERK) and phosphorylated-ERK (p-ERK) were analyzed by immunohistochemical staining.

Results:

2

Cisplatin treatment induced notable cardiac alteration

as evidenced by changes in cardiac morphology

elevated serum enzymes (

P

<

0.05)

ECG abnormalities

and increased left ventricular end-diastolic pressure (

P

<

0.05). Meanwhile

cisplatin sig

nificantly increased arterial pulse pressure (

P

<

0.01)

primarily due to a decrease in diastolic blood pressure. Severe fibrosis was also observed in the thoracic aorta wall. In vascular ring experiments

cisplatin treatment led to a significant reduction in phenylephrine-induced contraction (

P

<

0.05) and acetylcholine-induced relaxation (

P

<

0.01). Notably

Curcumin co-administration significantly alleviated cisplatin-induced cardiovascular damages

as demonstrated by improvement in these parameters. Furthermore

ERK expression in the myocardium and p-ERK expression in vascular smooth muscle cells were significantly upregulated following curcumin co-treatment.

Conclusions:

2

Curcumin protects the heart and vasculature from cisplatin-induced damages

likely by upregulating ERK/p-ERK expression. These findings suggest that curcumin may serve as a promising therapeutic strategy for mitigating cisplatin-associated cardiovascular toxicity during tumor chemotherapy.

In vitro

cell culture experiments are needed to clarify the underlying mechanism.