The potential risks of herbicide butachlor to immunotoxicity via induction of autophagy and apoptosis in the spleen.

Butachlor being an important member of chloroacetanilide herbicides, is frequently used in agriculture to control unwanted weeds. Exposure to butachlor can induce cancer, human lymphocyte aberration, and immunotoxic effects in animals. The current experimental trial was executed to determine the potential risks of herbicide butachlor to immunotoxicity and its mechanism of adverse effects on the spleen. For this purpose, mice were exposed to 8 mg/kg butachlor for 28 days, and the toxicity of butachlor on the spleen of mice was evaluated. We found that butachlor exposure led to an increase in serum ALB, GLU, TC, TG, and TP and changes in the morphological structure of the spleen of mice. More importantly, results showed that butachlor significantly increased the expression level of ATG-5, decreased the protein expression of LC3B and M-TOR, and significantly decreased the mRNA content of M-TOR and p62. Results revealed that the mRNA contents of APAF-1, CYTC, and CASP-9 related genes were significantly decreased after butachlor treatment. Subsequently, the mRNA levels of inflammatory cytokines (IL-1ß, TNF-α, IL-10) were reduced in the spleen of treated mice. This study suggested that butachlor induce spleen toxicity and activate the immune response of spleen tissue by targeting the CYTC/BCL2/M-TOR pathway and caspase cascading activation of spleen autophagy and apoptosis pathways which may ultimately lead to immune system disorders.

Iodonium Ylides as Carbene Precursors in Rh(III)-Catalyzed C-H Activation.

The rhodium(III)-catalyzed coupling of C-H substrates with iodonium ylides has been realized for the efficient synthesis of diverse cyclic skeletons, where the iodonium ylides have been identified as efficient and outstanding carbene precursors. The reaction systems are applicable to both sp2 and sp3 C-H substrates under mild and redox-neutral conditions. The catalyst loading can be as low as 0.5 mol % in a gram-scale reaction. Representative products exhibit cytotoxicity toward human cancer cells at nanomolar levels.

Rh(III)-Catalyzed Coupling of Acrylic Acids and Ynenones via Olefinic C-H Activation and Michael Addition.

Rh(III)-catalyzed coupling between acrylic acids and yndienones has been realized for the synthesis of cis-hydrobenzofuranone. The reaction proceeded in excellent regio- and stereoselectivity under mild and redox-neutral conditions via a sequence of carboxylic acid-directed olefinic C-H activation, alkyne insertion, and Michael addition. Representative products were found to exhibit cytotoxicity toward the A549 cancer cell line at micromolar levels.

Toxic effects of arsenic trioxide on spermatogonia are associated with oxidative stress, mitochondrial dysfunction, autophagy and metabolomic alterations.

Arsenic is a toxic metalloid that can cause male reproductive malfunctions and is widely distributed in the environment. The aim of this study was to investigate the cytotoxicity of arsenic trioxide (ATO) induced GC-1 spermatogonial (spg) cells. Our results found that ATO increased the levels of catalase (CAT) and malonaldehyde (MDA) and reactive oxygen species (ROS), while decreasing glutathione (GSH) and the total antioxidant capacity (T-AOC). Therefore, ATO triggered oxidative stress in GC-1 spg cells. In addition, ATO also caused severe mitochondrial dysfunction that included an increase in residual oxygen consumption (ROX), and decreased the routine respiration, maximal and ATP-linked respiration (ATP-L-R), as well as spare respiratory capacity (SRC), and respiratory control rate (RCR); ATO also damaged the mitochondrial structure, including mitochondrial cristae disordered and dissolved, mitochondrial vacuolar degeneration. Moreover, degradation of p62, LC3 conversion, increasing the number of acidic vesicle organelles (AVOs) and autophagosomes and autolysosomes are demonstrated that the cytotoxicity of ATO may be associated with autophagy. Meanwhile, the metabolomics analysis results showed that 20 metabolites (10 increased and 10 decreased) were significantly altered with the ATO exposure, suggesting that maybe there are the perturbations in amino acid metabolism, lipid metabolism, glycan biosynthesis and metabolism, metabolism of cofactors and vitamins. We concluded that ATO was toxic to GC-1 spg cells via inducing oxidative stress, mitochondrial dysfunction and autophagy as well as the disruption of normal metabolism. This study will aid our understanding of the mechanisms behind ATO-induced spermatogenic toxicity.