Rotenone and 3-bromopyruvate toxicity impacts electrical and structural cardiac remodeling in rats.

3-Bromopyruvate (3-BrPA) is a promising agent that has been widely studied in the treatment of cancer and pulmonary hypertension. Rotenone is a pesticide commonly used on farms and was shown to have anti-cancer activity and delay fibrosis progression in chronic kidney disease in a recent study. However, there are few studies showing the toxicity of rotenone and 3-BrPA in the myocardium. To support further medical exploration, it is necessary to clarify the side effects of these compounds on the heart. This study was designed to examine the cardiotoxicity of 3-BrPA and rotenone by investigating electrical and structural cardiac remodeling in rats. Forty male rats were divided into 4 groups (n = 10 in each group) and injected intraperitoneally with 3-BrPA, rotenone or a combination of 3-BrPA and rotenone. The ventricular effective refractory period (VERP), corrected QT interval (QTc), and ventricular tachycardia/ventricular fibrillation (VT/VF) inducibility were measured. The expression of Cx43, Kir2.1, Kir6.2, DHPRα1, KCNH2, caspase3, caspase9, Bax, Bcl2, and P53 was detected. Masson's trichrome, TUNEL, HE, and PAS staining and transmission electron microscopy were used to detect pathological and ultrastructural changes. Our results showed that rotenone alone and rotenone combined with 3-BrPA significantly increased the risk of ventricular arrhythmias. Rotenone combined with 3-BrPA caused myocardial apoptosis, and rotenone alone and rotenone combined with 3-BrPA caused electrical and structural cardiac remodeling in rats.

[Relationship between genetic polymorphism of interleukin-6 and pneumoconiosis].

OBJECTIVE: To explore the relationship between interleukin-6 (IL-6) (-634C/G) genetic polymorphisms and the pneumoconiosis. METHODS: A total of 104 male stage I pneumoconiosis patients diagnosed by the Pneumoconiosis Diagnosis Expert Panel according to the Chinese National Diagnosis Criteria of Pneumoconiosis (GBZ 70 - 2002) were selected. The pneumoconiosis comprised 66 silicosis and 38 coal worker' pneumoconiosis (CWP). A total of 122 workers exposed to same dusts as the patients but without pneumoconiosis including 77 exposed to silica dusts and 45 to coal dusts were selected. The patients and the controls had the same dust exposure history. The peripheral venous blood was drawn from each subject. The IL-6 (-634C/G) genetic polymorphisms were detected by polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLP) techniques. RESULTS: The frequencies of IL-6 (-634C/G) (CC, CG and GG) genotypes were 66.7%, 19.7% and 13.6% in silicosis group, 42.9%, 42.9% and 14.2% in silica dust exposure group, 73.7%, 18.4% and 7.9% in CWP group, 51.1%, 35.6% and 13.3% in coal dust exposure group respectively. The statistical analysis indicated that there was significant difference in the frequencies of IL-6 (-634C/G) (CC, CG and GG) genotypes between silicosis patients and workers exposed to silica dusts (P < 0.05). CONCLUSION: IL-6 (-634 C/G) genetic polymorphisms might play a role in the occurrence of silicosis.