RESUMEN
Heavy metals are common environmental industrial pollutants. Due to anthropogenic activity, chromium, especially its hexavalent form [Cr(VI)], is a widespread environmental contaminant that poses a threat to human health. In this review paper, we summarize the currently reported molecular mechanisms involved in chromium toxicity with a focus on the induction of pro-inflammatory non-apoptotic cell death pathways such as necroptosis, pyroptosis, and ferroptosis. The review highlights the ability of chromium to induce necroptosis, pyroptosis, and ferroptosis revealing the signaling pathways involved. Cr(VI) can induce RIPK1/RIPK3-dependent necroptosis both in vitro and in vivo. Chromium toxicity is associated with pyroptotic NLRP3 inflammasome/caspase-1/gasdermin D-dependent secretion of IL-1ß and IL-18. Furthermore, this review emphasizes the role of redox imbalance and intracellular iron accumulation in Cr(VI)-induced ferroptosis. Of note, the crosstalk between the investigated lethal subroutines in chromium-induced toxicity is primarily mediated by reactive oxygen species (ROS), which are suggested to act as a rheostat determining the cell death pathway in cells exposed to chromium. The current study provides novel insights into the pro-inflammatory effects of chromium, since necroptosis, pyroptosis, and ferroptosis affect inflammation owing to their immunogenic properties linked primarily with damage-associated molecular patterns. Inhibition of these non-apoptotic lethal subroutines can be considered a therapeutic strategy to reduce the toxicity of heavy metals, including chromium.
RESUMEN
OBJECTIVE: The aim is to study the trends in gastric cancer (GC) mortality in Kazakhstan. METHODS: Data on those who died from GC and on the annual population were obtained from the Bureau of National Statistics of the Agency for Strategic Planning and Reforms of the Republic of Kazakhstan. A retrospective study was carried out for the period 2009-2018 using descriptive and analytical methods of oncoepidemiology. The extensive, crude and age-specific mortality rates are determined according to the generally accepted methodology used in sanitary statistics. RESULTS: GC mortality in Kazakhstan is considered to be decreasing. It was determined that during the studied period 19,672 died of this cancer. The mean of death was 67.8 with 95% CI of 67.6 to 68.0. The highest mortality rates per 100,000 in the entire population were found in the age groups 75-79 years (145.9±24.1), 80-84 years (161.0±11.0), and 85+ years (116.5±16.4). Trends in age-related mortality rates had a pronounced tendency to increase in 70-74 years (T=+4.3%, R2=0.1924) and to decrease in the age of up to 30 (T=-8.7%, R2=0.2426). The average annual standardized mortality rate was 13.2 per 100,000, and in trends tended to decrease (T=-5.8%; R2=0.9763). In all regions, there is a decrease in mortality, except for the city of Astana. During categorization mortality rates were determined on the basis of standardized indicators: low - up to 12.9, average - from 12.9 to 15.1, high - above 15.1 per 100,000 for the entire population. CONCLUSION: The mortality rates from GC tend to decrease, while the downward trends and the degree of their approximation are expressed in almost all regions. The study of regional mortality has theoretical and practical significance for monitoring and evaluating the effectiveness of early detection and treatment. Health authorities should take into account the results obtained when organizing antitumor measures.