Unveiling the physical, behavioural, and biochemical effects of clothianidin on a non-target organism, Drosophila melanogaster

Clothianidin is a novel neonicotinoid pesticide globally used in agriculture to enhance crop production. However, unintentional exposure to clothianidin via contaminated environmental matrices and food products can be detrimental to non-target organisms, including humans. Hence, to unravel the potential health risks at organismal and sub-organismal levels, first instar larvae of a non-target organism, Drosophila melanogaster, were exposed to sub-lethal concentrations (0.05 to 0.1 μg/mL) of clothianidin till their third instar stage (chronic exposure). Larvae from the control and clothianidin-exposed groups were examined for their body weight, physical activity, behaviour, and enzymatic activities using in vivo and molecular docking approaches. Results have suggested that clothianidin at sub-lethal concentrations reduces body weight and physical fitness of D. melanogaster. Interestingly, AChE activity in larvae was reduced by 35 % and 41.13 % following exposure to 0.07 and 0.1 μg/mL of clothianidin, respectively. Further, the activity of mitoferrin, a major importer of iron inside the mitochondrial matrix and malate dehydrogenase, an integral component of the TCA cycle, were down-regulated by 58 % and 45.93 %, respectively, at 0.1 μg/mL clothianidin. Additionally, the activities of glucose 6-phosphate dehydrogenase, a vital enzyme of the pentose phosphate pathway and angiotensin-converting enzyme, responsible for maintaining optimum body physiology, were significantly declined by 43.58 % and 57.63 % at 0.1 μg/mL concentration of clothianidin. Binding affinity analyses have revealed that clothianidin can potentially bind with these enzymes using varying numbers of hydrogen bonds and other hydrophobic interactions to subvert their catalytic functions. Therefore, results of the present study equivocally suggest that chronic exposure to clothianidin, even at low concentrations, can disturb the physical, behavioural, and enzymatic activities of non-target organisms.