Acute exposure to environmentally relevant lead levels induces oxidative stress and neurobehavioral alterations in larval zebrafish (Danio rerio)

Abstract

The ubiquitous contamination of environmental lead (Pb) remains a worldwide threat.Improper Pb mine waste disposal from an abandoned lead-zinc mine has recently unearthed a widespread Pb poisoning in children in Kabwe Zambia. Although the adverse effects of Pb on human health have begun to receive attention, the ecotoxicological effects on aquatic vertebrates still need further investigation. In addition, there is paucity in the knowledge on the behavioural and molecular subcellular responses in larval zebrafish exposed to Pb within the range of environmental relevant concentration (average 3 µg/L with maximum of 94 µg/L) on aquatic organisms such as zebrafish. The adverse effects of environmentally relevant levels of Pb on larval zebrafish was evaluated by measuring swimming behaviour under alternating dark and light conditions. Larval zebrafish acutely exposed to environmentally relevant Pb exhibited neuro-behavioural alteration including enhanced hyperactivity under light conditions evidenced by increased distanced covered and speed compared to the control. The alteration of entire behavioral profiles was further associated with the disturbed expression patterns of mRNA level of key genes associated with antioxidant (HO-1, Ucp-2 and CoxI), proapoptotic gene (TP53), and antiapoptotic gene (Bcl-2). To our knowledge, this is the first report on the effects of environmentally relevant Pb levels from Kabwe, Zambia and their adverse neurobehavioural effects and subcellular molecular oxidative responses in larval zebrafish acutely exposed within a 30 minutes period. The current results would be beneficial in our understanding of the effects of low Pb levels acutely discharged into an aquatic environment and the life of aquatic organisms.

Morphological and Molecular Alterations Induced by Lead in Embryos and Larvae of Danio rerio

“…In zebrafish embryos, it has been previously reported that short-term exposure to high Pb concentrations induces increased ROS production and upregulation of the antioxidant enzymes [51]. We showed that two environmentally relevant concentrations of Pb induce a significant and time-dependent upregulation of sod1, a key antioxidant enzyme implicated in the first-line defense against oxidative stress [35,47,51,53,69,70]. Since Pb concentrations tested here are very low, our results reinforce the role of sod as sensitive and valuable biomarkers of lead-induced oxidative stress with important consequences thereof for the protection of aquatic life and human health.…”

“…Several endpoints have been evaluated to disclose signals of lead toxicity in fish sentinel species, including zebrafish. Neurotoxicity, oxidative stress induction, and hematological alterations are the mainly reported outcomes of lead exposure in both adults and embryos [8,[22][23][24]29,30,34,[44][45][46][47]. However, all these literature data relate to high lead concentrations, thus leaving a gap of knowledge regarding the adverse effects of lead at environmentally relevant concentrations [9,53].…”

“…In zebrafish embryos and larvae, available studies on Pb toxicity mainly focused on neurotoxicity, neurodevelopmental, and neurobehavior effects [40,[43][44][45][46][47][48]. Surprisingly, morpho-functional investigations during the sensitive phase of development are scarce, and only a few studies have furnished an overall morphological evaluation [45,[49][50][51][52][53].…”

Vitamin C Mitigates Oxidative Stress and Behavioral Impairments Induced by Deltamethrin and Lead Toxicity in Zebrafish

“…An independent testing at six Washington DC public schools in 2008 showed that 2–41% of sampled tap water has a Pb contamination problem, with the highest lead detected at 1987 μg L −1 , significantly higher than the EPA-recommended maximum level of 20 μg L −1 for schools [ 13 ]. As it is described in literature, in addition to its major neurotoxicity [ 14 , 15 , 16 , 17 , 18 , 19 ] the exposure to Pb has been linked to oxidative stress [ 20 ], cardiovascular toxicity [ 21 ], as well as gut microbiota dysbiosis and hepatic metabolic disorder [ 12 ] in zebrafish. Among the Pb-induced zebrafish neurobehavioral changes identified to date, learning and memory deficits, a decrease in the exploratory activities, altered social and aggressive behavior, color preference or responses to mechanosensory and visual stimuli are included [ 22 , 23 , 24 , 25 , 26 ].…”

“…The DM concentration in water samples ranged from ng L −1 to μg L −1 . Previous studies have reported that DM exposure could induce zebrafish developmental delay and malformation [ 38 , 39 , 40 ], apoptosis [ 38 , 40 ], cardiovascular toxicity [ 38 ], gonadotoxicity [ 41 ] as well as changes in neurochemical, behavioral and cognitive endpoints [ 20 , 38 , 39 , 42 , 43 , 44 ]. Hyperactivity and swimming towards the surfaces were observed in adult zebrafish after DM (>0.1 μg L −1 ) exposure [ 39 , 45 ].…”