Search

Accumulating evidence demonstrates that ferroptosis may be important in the pathophysiological process of traumatic brain injury (TBI). As a major hormone of the pineal gland, melatonin exerts many beneficial effects on TBI, but there is no information regarding the effects of melatonin on ferroptosis after TBI. As expected, TBI resulted in the time‐course changes of ferroptosis‐related molecules expression and iron accumulation in the ipsilateral cortex. Importantly, we found that treating with melatonin potently rescued TBI induced the changes mentioned above and improved functional deficits versus vehicle. Similar results were obtained with a ferroptosis inhibitor, liproxstatin‐1. Moreover, the protective effect of melatonin is likely dependent on melatonin receptor 1B (MT2). Although ferritin plays a vital role in iron metabolism by storing excess cellular iron, its precise function in the brain, and whether it involves melatonin's neuroprotection remain unexplored. Considering ferritin H (Fth) is expressed predominantly in the neurons and global loss of Fth in mice induces early embryonic lethality, we then generated neuron‐specific Fth conditional knockout (Fth‐KO) mice, which are viable and fertile but have altered iron metabolism. In addition, Fth‐KO mice were more susceptible to ferroptosis after TBI, and the neuroprotection by melatonin was largely abolished in Fth‐KO mice. In vitro siFth experiments further confirmed the results mentioned above. Taken together, these data indicate that melatonin produces cerebroprotection, at least partly by inhibiting neuronal Fth‐mediated ferroptosis following TBI, supporting the notion that melatonin is an excellent ferroptosis inhibitor and its anti‐ferroptosis provides a potential therapeutic target for treating TBI. [ABSTRACT FROM AUTHOR]

BACKGROUND Silkworm ( Bombyx mori) is an economically important insect. It is relatively less resistant to certain chemicals and environment exposures such as pesticides and pathogens. After pesticide exposures, the silkworms are more susceptible to microbial infections. The mechanism underlying the susceptibility might be related to immune response and oxidative stress. RESULTS A sublethal dose of phoxim combined with Bombyx mori nucleopolyhedrovirus (BmNPV) elevated the silkworm mortality at 96 h. We found a higher content of H2O2 and increased levels of genes related to oxidative stress and immune response after treatment with a sublethal dose of phoxim for 24 h or 48 h. However, such response decreased with longer pesticide treatment. Mortality increased by 44% when B. mori was exposed to combined treatment with BmNPV and phoxim rather than BmNPV alone. The level of examined immune-related and oxidative-stress-related genes significantly decreased in the combined treatment group compared with the BmNPV group. Our results indicated that, with long-term exposure to pesticides such as OPs, even at sublethal dose, the oxidative stress response and immune responses in silkworm were inhibited, which may lead to further immune impairment and accumulation of oxidative stress, resulting in susceptibility to the virus and harm to the silkworm. CONCLUSION Our study provided insights for understanding the susceptibility to pathogen after pesticide exposures, which may promote the development of better pesticide controls to avoid significant economic losses. © 2016 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

ABSTRACT Organophosphate pesticides are applied widely in the world for agricultural purposes, and their exposures often resulted in non-cocooning of Bombyx mori in China. Silkworm midgut is the major organ for digestion and nutrient absorption, importantly it is also a barrier against foreign substances and chemical pesticides. The purpose of this study was to determine the mechanism of oxidative injury in silkworm midgut with phoxim induction. The results showed that the transcription level of oxidative phosphorylation signaling pathway genes of midgut under phoxim stress. Digital gene expression (DGE) analysis revealed that 24 electron transport chain (ETC)-related genes were upregulated. Quantitative real time polymerase chain reaction results indicated that the ETC the genes encoding NADH-CoQ1, Succinic-Q, cyt c reductase-S, cyt c oxidase-S, cytochrome c oxidase polypeptide IV, ATP synthase, and vacuolar H+ ATP synthase were all significantly up-regulated by 1.50-, 1.31-, 1.42-, 1.44-, 1.70-, 2.03- and 1.43-fold, respectively. Phoxim induction enhanced the activity of ETC complex in mitochondria, and induced the accumulation of ROS in midgut. These results indicated that trace phoxim enhanced respiration in midgut, and the imbalance between the activity changes of ETC may led to reactive oxygen species accumulation. The ETC of mitochondria may be potential biomarkers of midgut toxicity in B. mori caused by phoxim exposure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 167-175, 2017. [ABSTRACT FROM AUTHOR]

Florfenicol (FF) is a new antibiotic commonly used in sericulture. This study aimed to examine the effects of low (LC: 0.06 g/L), medium (MC: 0.12 g/L), and high (HC: 1.2 g/L) concentrations of FF on the midgut physiological functions of the silkworm, Bombyx mori (L.) (Lepidoptera: Bombycidae). The results showed that the body weight and the whole cocoon weight of silkworms decreased and the development duration of the fifth instar was prolonged in the HC group. The structure of intestinal microbiota of silkworm larvae was changed by high FF exposure. Specifically, the abundance of conditional pathogens (Curtobacterium, Sanguibater, etc.) was significantly increased, whereas the abundance of Pseudomonas and Pedobacter was decreased significantly. Additionally, the intestinal reactive oxygen species level at 72 h was significantly elevated, and the muscle layer had become loose, together with the appearance of gut goblet cell atrophy. We observed that the increase in Lactobacillus abundance led to a reduction in intestinal fluid pH, resulting in decreased α‐amylase and protease activities, whereas lipase activity exhibited an elevation. The results demonstrated that the accumulation of peroxides induced by exposure to 1.2 g/L FF caused intestinal damage, and the decrease in pH resulting from alterations in microbial composition and structure affected digestive enzyme activity, collectively leading to physiological impairment of the silkworm midgut. These findings provide a valuable reference for the safe use of FF in sericulture. [ABSTRACT FROM AUTHOR]