Duration-dependent mild heat stress attenuates mercury-induced Neuroreproductive and oxidative toxicity in Drosophila melanogaster via hormetic mechanisms.

Mercury is a ubiquitous environmental pollutant that interferes with neurological and reproductive functions through oxidative stress, inflammation, and genomic instability. Although mild heat stress can induce hormesis to combat environmental insults, the ability of heat stress to ameliorate heavy-metal-induced toxicity and the importance of exposure duration remain poorly defined. This study investigated whether short-term thermal stress modulates mercuric chloride (HgCl₂) toxicity in D. melanogaster. Adult flies were exposed to HgCl₂ (10 mM) alone or concurrently with mild heat stress (37 °C) for 5 or 15 min. Survival, locomotor performance, reproductive fitness, redox homeostasis, membrane ATPase activities, nitric oxide levels, dopamine content, DNA fragmentation, and brain histoarchitecture were assessed. HgCl₂ exposure significantly reduced survival, locomotor activity, fecundity, antioxidant capacity, ATPase activities, and dopamine levels, while increasing oxidative stress markers, nitric oxide production, DNA fragmentation, and neurodegenerative changes in the brain. Co-exposure to 5 min of heat stress markedly attenuated HgCl₂-induced toxicity, improving survival, neuromuscular performance, reproductive output, redox balance, dopamine levels, and brain cytoarchitecture. In contrast, 15 min of heat stress provided limited attenuation and, when applied independently, induced mild toxicity at several endpoints. Protective effects were accompanied by partial restoration of thiol status, suppression of xanthine oxidase activity, normalisation of nitric oxide levels, preservation of Na⁺/K⁺- and Ca2⁺-ATPase activities, and reduced genomic DNA fragmentation. These findings demonstrate a duration-dependent hormetic interaction between thermal stress and HgCl₂ toxicity, wherein brief heat exposure confers multisystem protection, whereas prolonged exposure negates this benefit. The study highlights the importance of precise stress calibration and supports mild, non-pharmacological interventions as potential modulators of heavy metal toxicity, with relevance for environmentally exposed populations.