Division of Environmental Health and Toxicology, Nitte (Deemed to be University), Nitte University Centre for Science Education and Research (NUCSER), Mangaluru, India.
Division of Food Safety and Nutrition, Nitte (Deemed to be University), Nitte University Centre for Science Education and Research (NUCSER), Mangaluru, India.
Environ Toxicol. 2022 Jul;37(7):1723-1739. doi: 10.1002/tox.23520. Epub 2022 Mar 18.
Benzene, a ubiquitous environmental chemical, is known to cause immune dysfunction and developmental defects. This study aims to investigate the relation between benzene-induced immune dysfunction and developmental toxicity in a genetically tractable animal model, Drosophila melanogaster. Further, the study explored the protective role of Heat Shock Protein 70 (Hsp70) against benzene-induced immunotoxicity and subsequent developmental impact. Drosophila larvae exposed to benzene (1.0, 10.0, and 100.0 mM) were examined for total hemocyte (immune cells) count, phagocytic activity, oxidative stress, apoptosis, and their developmental delay and reduction were analyzed. Benzene exposure for 48 h reduced the total hemocytes count and phagocytic activity, along with an increase in the Reactive Oxygen Species (ROS), and lipid peroxidation in the larval hemocytes. Subsequently, JNK-dependent activation of the apoptosis (Caspase-3 dependent) was also observed. During their development, benzene exposure to Drosophila larvae led to 3 days of delay in development, and 40% reduced adult emergence. Hsp70-overexpression in hemocytes was found to mitigate benzene-induced oxidative stress and abrogated the JNK-mediated apoptosis in hemocytes, thus restoring total hemocyte count and improving phagocytotic activity. Further, hsp70-overexpression in hemocytes also lessened the benzene-induced developmental delay (rescue of 2.5 days) and improved adult emergence (20%) emergence, revealing a possible control of immune cells on the organism's development and survival. Overall, this study established that hsp70-overexpression in the Drosophila hemocytes confers protection against benzene-induced immune injury via regulating the ROS/JNK signaling pathway, which helps in the organism's survival and development.
苯是一种普遍存在于环境中的化学物质，已知其会导致免疫功能障碍和发育缺陷。本研究旨在利用遗传上易于操作的动物模型——黑腹果蝇，探究苯诱导的免疫功能障碍与发育毒性之间的关系。此外，本研究还探讨了热休克蛋白 70（Hsp70）对苯诱导的免疫毒性及其随后的发育影响的保护作用。检测暴露于苯（1.0、10.0 和 100.0mM）的果蝇幼虫的总血细胞（免疫细胞）计数、吞噬活性、氧化应激、细胞凋亡情况，并分析其发育延迟和减少情况。暴露于苯 48 小时会降低总血细胞计数和吞噬活性，同时增加幼虫血细胞中的活性氧（ROS）和脂质过氧化。随后，还观察到 JNK 依赖性细胞凋亡（Caspase-3 依赖性）的激活。在发育过程中，苯暴露会导致果蝇幼虫发育延迟 3 天，成虫出现率降低约 40%。在血细胞中过表达 Hsp70 被发现可以减轻苯诱导的氧化应激，并阻断 JNK 介导的血细胞凋亡，从而恢复总血细胞计数并改善吞噬活性。此外，血细胞中 hsp70 的过表达也减轻了苯诱导的发育延迟（挽救 2.5 天）并提高了成虫出现率（提高约 20%），这表明免疫细胞可能对机体的发育和生存具有控制作用。总的来说，本研究表明，在果蝇血细胞中过表达 hsp70 通过调节 ROS/JNK 信号通路，为机体的生存和发育提供了对苯诱导的免疫损伤的保护作用。
