Rhu (anthraquinone purgatives) had apparent effect on inducing MC; its molecular mechanism is maybe to destroy intestinal mucosal barrier and advance proinflammatory factor TNF-α releasing, which leads to colonic epithelial cells apoptosis, and finally induce the change of MC due to the deposition of brown pigments, i.e. the macrophage phagocytized apoptotic body, on the colonic membrane.

Epidemiological studies have demonstrated an association between sulfur dioxide (SO2) and an increase of morbidity and mortality of cardiovascular diseases, such as ischemic heart disease, heart failure, and arrhythmia. Mitochondrion is the most sensitive organelle in myocardium of animals exposed to SO2 Here we study the molecular characterization of mitochondrial dysfunction in cardiac muscles of rat after SO2 exposure. We found that the cytochrome c oxidase (COX) activity, mitochondrial membrane potential (ΔΨm), ATP contents, mitochondrial DNA (mtDNA) contents, and mRNA expression of complexes IV and V subunits encoded by mtDNA were decreased after NaHSO3 treatment in vitro or SO2 inhalation in vivo The mitochondrial dysfunctions were accompanied by depressions of co-activator of peroxisome proliferator activated receptor gamma (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (TFAM) mRNA and protein. We observed swollen mitochondria and lower amounts of cristae in hearts of rats after 3.5 mg/m(3) SO2 inhalation for 30 days. Interestingly, NaHSO3 induced mitochondrial dysfunctions marked by ΔΨm and ATP reduction could be inhibited by an antioxidant N-acetyl-L-cysteine (NALC), accompanied by the restoration of transcriptional factors expressions. The cardiac mitochondrial dysfunctions could also be alleviated by overexpression of TFAM. SO2 induced abnormal left ventricular function was restored by NALC in vivo Our findings demonstrate that SO2 induces cardiac and mitochondrial dysfunction. And inhibition of reactive oxygen species and enhancing the transcriptional network controlling mitochondrial biogenesis can mitigate the SO2-induced mitochondrial dysfunction.

BackgroundCardiovascular disease is the leading cause of mortality in the advanced world, and age is an important determinant of cardiac function. The purpose of the study is to determine whether the PM2.5-induced cardiac dysfunction is age-dependent and whether the adverse effects can be restored after PM2.5 exposure withdrawal.MethodsFemale C57BL/6 mice at different ages (4-week-old, 4-month-old, and 10-month-old) received oropharyngeal aspiration of 3 mg/kg b.w. PM2.5 every other day for 4 weeks. Then, 10-month-old and 4-week-old mice were exposed to PM2.5 for 4 weeks and withdrawal PM2.5 1 or 2 weeks. Heart rate and systolic blood pressure were measured using a tail-cuff system. Cardiac function was assessed by echocardiography. Left ventricles were processed for histology to assess myocardial fibrosis. ROS generation was detected by photocatalysis using 2′,7′-dichlorodihydrofluorescein diacetate (DCFHDA). The expression of cardiac fibrosis markers (Col1a1, Col3a1) and possible signaling molecules, including NADPH oxidase 4 (NOX-4), transforming growth factor β1 (TGFβ1), and Smad3, were detected by qPCR and/ or Western blot.ResultsPM2.5 exposure induced cardiac diastolic dysfunction of mice, elevated the heart rate and blood pressure, developed cardiac systolic dysfunction of 10-month-old mice, and caused fibrosis in both 4-week-old and 10-month-old mice. PM2.5 exposure increased the expression of Col1a1, Col3a1, NOX-4, and TGFβ1, activated Smad3, and generated more reactive oxygen species in the myocardium of 4-week-old and 10-month-old mice. The withdrawal from PM2.5 exposure restored blood pressure, heart rate, cardiac function, expression of collagens, and malonaldehyde (MDA) levels in hearts of both 10-month-old and 4-week-old mice.ConclusionJuvenile and older mice are more sensitive to PM2.5 than adults and suffer from cardiac dysfunction. PM2.5 exposure reversibly elevated heart rate and blood pressure, induced cardiac systolic dysfunction of older mice, and reversibly induced fibrosis in juvenile and older mice. The mechanism by which PM2.5 exposure resulted in cardiac lesions might involve oxidative stress, NADPH oxidase, TGFβ1, and Smad-dependent pathways.Electronic supplementary materialThe online version of this article (10.1186/s12989-018-0264-2) contains supplementary material, which is available to authorized users.

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