Analysis of toxicity effects of delta-9-tetrahydrocannabinol on isolated rat heart mitochondria.

Mitochondria have the main roles in myocardial tissue homeostasis, through providing ATP for the vital enzymes in intermediate metabolism, contractile apparatus and maintaining ion homeostasis. Mitochondria-related cardiotoxicity results from the exposure with illicit drugs have previously reported. These illicit drugs interference with processes of normal mitochondrial homeostasis and lead to mitochondrial dysfunction and mitochondrial-related oxidative stress. Cannabis consumption has been shown to cause ventricular tachycardia, to increase the risk of myocardial infarction (MI) and potentially sudden death. Here, we investigated this hypothesis that delta-9-tetrahydrocannabinol (Delta-9-THC) as a main cannabinoid found in cannabis could directly cause mitochondrial dysfunction. Cardiac mitochondria were isolated with mechanical lysis and differential centrifugation form rat heart. The isolated cardiac mitochondria were treated with different concentrations of THC (1, 5, 10, 50, 100 and 500 µM) for 1 hour at 37 °C. Then, succinate dehydrogenase (SDH) activity, mitochondrial swelling, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) collapse and lipid peroxidation were measured in the treated and nontreated isolated cardiac mitochondria. Our observation showed that THC did not cause a deleterious alteration in mitochondrial functions, ROS production, MMP collapse, mitochondrial swelling, oxidative stress and lipid peroxidation in used concentrations (5-100 µM), even in several tests, toxicity showed a decreasing trend. Altogether, the results of the current study showed that THC is not directly toxic in isolated cardiac mitochondria, and even may be helpful in reducing mitochondrial toxicity.

Increasing probability of mortality during Indian heat waves.

Rising global temperatures are causing increases in the frequency and severity of extreme climatic events, such as floods, droughts, and heat waves. We analyze changes in summer temperatures, the frequency, severity, and duration of heat waves, and heat-related mortality in India between 1960 and 2009 using data from the India Meteorological Department. Mean temperatures across India have risen by more than 0.5°C over this period, with statistically significant increases in heat waves. Using a novel probabilistic model, we further show that the increase in summer mean temperatures in India over this period corresponds to a 146% increase in the probability of heat-related mortality events of more than 100 people. In turn, our results suggest that future climate warming will lead to substantial increases in heat-related mortality, particularly in developing low-latitude countries, such as India, where heat waves will become more frequent and populations are especially vulnerable to these extreme temperatures. Our findings indicate that even moderate increases in mean temperatures may cause great increases in heat-related mortality and support the efforts of governments and international organizations to build up the resilience of these vulnerable regions to more severe heat waves.