BackgroundChronic fructose consumption is associated with development of obesity, insulin resistance (IR) and metabolic syndrome (MS). Cardiovascular diseases are linked to metabolic deregulation observed in MS. N-acetylcysteine (NAC) is a sulfur containing compound of Allium plants (such as garlic and onion) that increases intracellular reduced glutathione concentrations, which is an endogenous antioxidant. MethodsThis study investigated the ability of N-acetyl cysteine (NAC) to alleviate the metabolic disorders in fructose-induced MS in male Wistar rats and to examine its protective effect on aortic and cardiac tissues via its in uence on cardiotrophin-1 (CT-1) expression. NAC (20 mg/kg b.w./day) was administered to fructose (20% w/v) induced MS animals for twelve weeks. ResultsChronic fructose consumption increased body weight gain, relative heart weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), IR and associated with metabolic alterations. Histological and immunohistochemical examination revealed aortic stiffness and myocardial degeneration and brosis together with increased CT-1 expression. Treatment with NAC improved IR, SBP, DBP and mitigated atherogenic dyslipidaemia and oxidative stress (OS). Additionally, NAC down-regulated CT-1 expression in the heart and aorta. Furthermore, CT-1 expression in the heart and aorta was positively correlated with basal glycemia, nal SBP and DBP, total cholesterol, triglycerides, low density lipoproteins and negatively correlated with high density lipoproteins levels. ConclusionThe ndings reported here demonstrated, for the rst time, the protective effect of NAC against aortic and myocardial degeneration and brosis through down-regulation of CT-1 in fructose induced MS animal model. Also, our results revealed the infallible role of NAC to blunt the cardiometabolic deregulation observed in MS.

Docetaxel (DTX) is the treatment of choice for metastatic castration-resistant prostate cancer. However, developing drug resistance is a significant challenge for achieving effective therapy. This study evaluated the anticancer and synergistic effects on DTX of four natural compounds (calebin A, 3′-hydroxypterostilbene, hispolon, and tetrahydrocurcumin) using PC-3 androgen-resistant human prostate cancer cells. We utilized the CellTiter-Glo® luminescent cell viability assay and human PC-3 androgen-independent prostate cancer cells to determine the antiproliferative effects of the four compounds alone and combined with DTX. Cytotoxicity to normal human prostate epithelial cells was tested in parallel using normal immortalized human prostate epithelial cells (RWPE-1). We used cell imaging and quantitative caspase-3 activity to determine whether these compounds induce apoptosis. We also measured the capacity of each drug to inhibit TNF-α-induced NF-kB using a colorimetric assay. Our results showed that all four natural compounds significantly augmented the toxicity of DTX to androgen-resistant PC-3 prostate cancer cells at IC50. Interestingly, when used alone, each of the four compounds had a higher cytotoxic activity to PC-3 than DTX. Mechanistically, these compounds induced apoptosis, which we confirmed by cell imaging and caspase-3 colorimetric assays. Further, when used either alone or combined with DTX, the four test compounds inhibited TNF-α-induced NF-kB production. More significantly, the cytotoxic effects on normal immortalized human prostate epithelial cells were minimal and non-significant, suggesting prostate cancer-specific effects. In conclusion, the combination of DTX with the four test compounds could effectively enhance the anti-prostate cancer activity of DTX. This combination has the added value of reducing the DTX effective concentration. We surmise that calebin A, 3′-hydroxypterostilbene, hispolon, and tetrahydrocurcumin were all excellent drug candidates that produced significant antiproliferative activity when used alone and synergistically enhanced the anticancer effect of DTX. Further in vivo studies using animal models of prostate cancer are needed to confirm our in vitro findings.

Background Chronic fructose consumption is associated with development of obesity, insulin resistance (IR) and metabolic syndrome (MS). Cardiovascular diseases are linked to metabolic deregulation observed in MS. N-acetylcysteine (NAC) is a sulfur containing compound of Allium plants (such as garlic and onion) that increases intracellular reduced glutathione concentrations, which is an endogenous antioxidant. Methods This study investigated the ability of N-acetyl cysteine (NAC) to alleviate the metabolic disorders in fructose-induced MS in male Wistar rats and to examine its protective effect on aortic and cardiac tissues via its influence on cardiotrophin-1 (CT-1) expression. NAC (20 mg/kg b.w./day) was administered to fructose (20% w/v) induced MS animals for twelve weeks. Results Chronic fructose consumption increased body weight gain, relative heart weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), IR and associated with metabolic alterations. Histological and immunohistochemical examination revealed aortic stiffness and myocardial degeneration and fibrosis together with increased CT-1 expression. Treatment with NAC improved IR, SBP, DBP and mitigated atherogenic dyslipidaemia and oxidative stress (OS). Additionally, NAC down-regulated CT-1 expression in the heart and aorta. Furthermore, CT-1 expression in the heart and aorta was positively correlated with basal glycemia, final SBP and DBP, total cholesterol, triglycerides, low density lipoproteins and negatively correlated with high density lipoproteins levels. Conclusion The findings reported here demonstrated, for the first time, the protective effect of NAC against aortic and myocardial degeneration and fibrosis through down-regulation of CT-1 in fructose induced MS animal model. Also, our results revealed the infallible role of NAC to blunt the cardiometabolic deregulation observed in MS.