Hsp70 overexpression in Drosophila hemocytes attenuates benzene‐induced immune and developmental toxicity via regulating ROS/JNK signaling pathway

Abstract

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.

Daily Exposure to Environmental Volatile Organic Compounds Triggers Oxidative Damage: Evidence from a Large-Scale Survey in China

“…Exposure to benzene (50 mM) for 4 h at 37 °C induced ROS formation in lymphocytes isolated from healthy individuals . Additionally, a significant increase in intracellular ROS levels was observed in Drosophila melanogaster larvae exposed to benzene . In a metabolome-wide association study of occupational exposure to benzene, it is found that benzene exposure alters oxidation metabolites in workers .…”

“…70 Additionally, a significant increase in intracellular ROS levels was observed in Drosophila melanogaster larvae exposed to benzene. 71 In a metabolomewide association study of occupational exposure to benzene, it is found that benzene exposure alters oxidation metabolites in workers. 72 Nevertheless, further studies are warranted to verify these preliminary findings since the single-spot urine sampling strategy may not necessarily reflect long-term adverse health effects.…”

Fear-of-intimacy-mediated zinc transport is required for Drosophila fat body endoreplication

“…It is known that the JNK signaling cascade is a mitogen-activated protein kinase (MAPK) signaling pathway that can be activated in response to a wide range of environmental stimuli [57]. Many diseases, such as neurodegenerative disorders, cancer, diabetes, cardiovascular diseases, and immune system disorders, are associated with the JNK signaling pathway activated by oxidative stress [58][59][60][61]. Here, we provide evidence for the role of the ROS-JNK pathway in fat body growth defects caused by zinc deficiency when foi was knocked down.…”

Toxicity Assessment of Curculigo orchioides Leaf Extract Using Drosophila melanogaster: A Preliminary Study

“…Green master mix (RR820A, TAKARA, Japan). The relative quantification of gene transcript expression was performed by amplifying β-actin as an internal control [ 29 ].…”

“…The larval gut immunostaining was performed as described by D’Souza et al [ 29 ]. The first instar larvae were transferred to control, and A.L.…”