Chronic toxicity of methamphetamine: Oxidative remodeling of pulmonary arteries.

Chronic toxicity of methamphetamine: Oxidative remodeling of pulmonary arteries. Toxicol In Vitro. 2019 Oct 16;:104668 Authors: Liang LY, Wang MM, Liu M, Zhao W, Wang X, Shi L, Zhu MJ, Zhao YL, Liu L, Maurya P, Wang Y Abstract Methamphetamine (MA) has a high uptake in lung, but the precise mechanism of MA-induced lung toxicity remains unclear. The aim of this study is to investigate the role of MA abuse in remodeling of pulmonary arteries and to explore the possible correlation of the association of the remodeling with the redox imbalance in pulmonary arterial smooth muscle cells (PASMCs). Wistar rats were randomly divided into control group and MA group for the experimental study. We employed H&E staining, western blot, immunofluorescence, knockdown, flow in our experimental approach. Our studies shows that chronic exposure to MA led to weight loss, increased pulmonary arterial pressure, hypertrophy of right ventricle and remodeling of pulmonary arterial wall of rats. Our cell culture study with PASMCs indicates that MA significantly induced the imbalance between proliferation and apoptosis by upregulating the level of PCNA, Bcl-2 and reduction in the expression of BAX and Caspase 3. MA markedly prevented the nuclear translocation of Nrf2 to inhibit antioxidation. The knockdown of Nrf2 expression using siRNA significantly elevated the expression of SOD2/GCS and the production of ROS in PASMCs and even scaled up the amount of PAS...
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research