Brain Protection by Methylene Blue and Its Derivative, Azur B, via Activation of the Nrf2/ARE Pathway in Cisplatin-Induced Cognitive Impairment

Cisplatin is a cytotoxic chemotherapeutic drug that leads to DNA damage and is used in the treatment of various types of tumors. However, cisplatin has several serious adverse effects, such as deterioration in cognitive ability. The aim of our work was to study neuroprotectors capable of preventing cisplatin-induced neurotoxicity. Methylene blue (MB) and AzurB (AzB) are able to neutralize the neurotoxicity caused by cisplatin by protecting nerve cells as a result of the activation of the Ntf2 signaling pathway. We have shown that cisplatin impairs learning in the Morris water maze. This is due to an increase in the amount of mtDNA damage, a decrease in the expression of most antioxidant genes, the main determinant of the induction of which is the Nrf2/ARE signaling pathway, and genes involved in mitophagy regulation in the cortex. The expression of genes involved in long-term potentiation was suppressed in the hippocampus of cisplatin-injected mice. MB in most cases prevented cisplatin-induced impairment of learning and decrease of gene expression in the cortex. AzB prevented the cisplatin-induced decrease of genes in the hippocampus. Also, cisplatin induced disbalance in the gut microbiome, decreased levels of Actinotalea and Prevotella, and increased levels of Streptococcus and Veillonella. MB and AzB also prevented cisplatin-induced changes in the bacterial composition of the gut microbiome

Microbiota of Cow’s Milk with Udder Pathologies

Mastitis is the most common disease for cattle, causing great economic losses for the global dairy industry. Recent studies indicate the multi-agent and microbiome diversity of this disease. To understand the nature of mastitis and investigate the role of the microbiome in the development of pathologies in the udder of bovines, we performed NGS sequencing of the 16S rRNA gene of cow’s milk with pathologies of the udder. The obtained data show a significant increase in the Cutibacterium, Blautia, Clostridium sensu stricto 2, Staphylococcus, Streptococcus and Microbacterium genera for groups of cows with udder pathologies. Increasing relative abundance of the Staphylococcus and Streptococcus genera was associated with subclinical mastitis. Our data show that a relative increase in abundance of the Staphylococcus and Microbacterium genera may be an early sign of infection. We have shown, for the first time, an increase in the Colidextribacter, Paeniclostridium and Turicibacter genera in groups of cows with mastitis. These results expand our understanding of the role of the microbiome in the development of bovine mastitis