Exposure to zinc oxide nanoparticles (ZnO-NPs) induces cardiovascular toxicity and exacerbates pathogenesis - Role of oxidative stress and MAPK signaling.

The precise toxico-pathogenic effects of zinc oxide nanoparticles (ZnO-NPs) on the cardiovascular system under normal and cardiovascular disease (CVD) risk factor milieu are unclear. In this study, we have investigated the dose-dependent effects of ZnO-NPs on developing chicken embryo and cell culture (H9c2 cardiomyoblast, HUVEC and aortic VSMC) models. In addition, the potentiation effect of ZnO-NPs on simulated risk factor conditions was evaluated using; 1. Reactive oxygen species (ROS) induced cardiac remodeling, 2. Angiotensin-II induced cardiac hypertrophy, 3. TNF-α induced HUVEC cell death and 4. Inorganic phosphate (Pi) induced aortic VSMC calcification models. The observed results illustrates that ZnO-NPs exposure down regulates vascular development and elevates oxidative stress in heart tissue. At the cellular level, ZnO-NPs exposure reduced the cell viability and increased the intracellular ROS generation, lipid peroxidation and caspase-3 activity in a dose-dependent manner in all three cell types. In addition, ZnO-NPs exposure significantly suppressed the endothelial nitric oxide (NO) generation, cardiac Ca2+ - ATPase activity and enhanced the cardiac mitochondrial swelling. Moreover, inhibition of p38 MAPK and JNK signaling pathways influence the cytotoxicity. Overall, ZnO-NPs exposure affects the cardiovascular system under normal conditions and it exacerbates the cardiovascular pathogenesis under selected risk factor milieu.

Diosgenin attenuates vascular calcification in chronic renal failure rats.

Vascular calcification due to elevated phosphate levels is the major contributor of cardiovascular dysfunction. The oxidative stress and gene expression events modulate the transdifferentiation of vascular smooth muscle cells into osteogenic phenotype. This present study intends to evaluate the dose-dependent effect of diosgenin, an antioxidant on high phosphate induced vascular calcification in adenine-induced chronic renal failure rats. High phosphate environment causes elevated calcium accumulation with related histological changes and alkaline phosphatase activity in aorta. Further it downregulates the activity of enzymatic antioxidants and elevates the level of lipid peroxidative markers. Moreover, the renal failure leads to reduced nitric oxide production. But, treatment with diosgenin at a dose of 10, 20, and 40 mg/kg given via oral gavages causes reversion of all the above events in a dose-dependent manner. The highest dose has shown more potential activity than other two doses, which has the ability to protect the alteration of liver markers and red blood cell antioxidant system without any adverse effects and it does not alter the kidney associated changes too. Finally, the Fourier transform infrared spectroscopy study strongly supports its ability to protect the macromolecules from oxidative stress. All the above evidences show that diosgenin has overall benefits against renal failure-induced vascular calcification-associated oxidative stress.

Molecular metabolic fingerprinting approach to investigate the effects of borneol on metabolic alterations in the liver of nitric oxide deficient hypertensive rats.

Hypertension is one of the major risk factor that underlie a wide range of cardiovascular irregularities which causes functional and metabolic alterations in vascular system and major organs. Nitric oxide is the central regulator of the vascular system and its deficiency leads to increased blood pressure and metabolic alterations in liver. Fourier transform infrared spectroscopy (FTIR) is a vibrational spectroscopic technique that uses infrared radiation to vibrate molecular bonds with in the sample that absorbs it and different samples contain diverse configurations of molecular bonds. Both wavenumber and area of the vibrational spectra can be used to explore the qualitative and quantitative constituent of macromolecules. In this study, we intended to evaluate the protective role of borneol, a natural terpene on liver metabolism in a nitric oxide deficient model of hypertension through interpretation of FTIR spectral information. Results demonstrate that FTIR can successfully indicate the molecular changes that occur in all groups. The over all findings demonstrate that in nitric oxide deficient animal model of hypertension, the liver metabolic program is altered through increasing the structural modification in proteins and triglycerides, and quantitative alteration in proteins, lipids, and glycogen. All the above mentioned modifications were protected by borneol in liver and showed its ability to exert a novel defensive action on hepatic metabolism.