Effect of long-term crotonaldehyde exposure on heart damage in male rats

Abstract

Objective: To observe the effect of long term crotonaldehyde exposure on heart damage in male rats, and to explore the possible mechanism of toxic action. Methods: 24 specific pathogen free healthy male wistar rats were randomly divided into 4 groups with 6 rats in each group. Rats were treated with with 8.5, 4.5, 2.5 and 0.0 mg/kg body weight crotonaldehyde by gavage, once a day for consecutive 150 days. After the last treatment, they were anesthetized and collected blood samples by cardiac puncture. The heart was rapidly separated after cervical dislocation. The cardiac organ coefficient was calculated and the histopathology changes in heart were observed by HE staining. At the same time, the activities of creatine kinase (CK) , lactate dehydrogenase-L (LDH-L) in serum were determined by automatic biochemical analyzer. Moreover, the levels of cardiac troponin (cTnT) , Angiotensin Ⅱ (Ang Ⅱ) , Brain natriuretic peptide (BNP) , Aldosterone (ALD) and interleukin (IL) -6, 8, 1β, interferon (IFN) -γ and tumor necrosis factor (TNF) -α in heart were determined by enzyme linked immunosorbent assay. Results: At the 90d, 120 d, and 150 d exposure, compared with the control group, the body weight gain in 4.5 and 8.5 mg/kg groups were decreased. Moreover, the heart weight in 4.5 and 8.5 mg/kg groups, and heart coefficient in 8.5 mg/kg group were decreased (P<0.05) . With the increasing dosage of crotonaldehyde, the degree of pathological changes in the heart of exposed rats were aggravated. The major pathological changes of heart in 4.5 and 8.5 mg/kg groups could be summarized as lymphocyte infiltration, abnormal cardiac muscle fiber arrangements, necrosis and fibrous connective tissue hyperplasia. Compared with the control group, the serum CK activity in 4.5 mg/kg group, CK and LDH-L activitivies in 8.5 mg/kg group were increased (P<0.05) ; Compared with the control group, the levels of ALD and ANGII in the heart of 4.5 and 8.5 mg/kg groups were increased, BNP level were decreased, and cTNT level in 8.5 mg/kg group were increased (P<0.05) . Compared with the control group, the levels of IL-1β、IL-6、IL-8 in 4.5 mg/kg group and IL-1β、IL-6、IL-8、TNF-α、IFN-γ in 8.5 mg/kg group were increased (P<0.05) . Conclusion: Crotonaldehyde could up-regulate cardiac inflammatory cytokines and alter the balance ofangiotensin-aldosterone-brain natriuretic peptide causing heart damage.