Impairment of Mitochondrial-Nuclear Cross Talk in Lymphocytes Exposed to Landfill Leachate

Abstract

Landfill leachate, a complex mixture of different solid waste compounds, is widely known to possess toxic properties. However, the fundamental molecular mechanisms engaged with landfill leachate exposure inducing cellular and sub-cellular ramifications are not well explicated. Therefore, we aim to examine the potential of leachate to impair mitochondrial machinery and its associated mechanisms in human peripheral blood lymphocytes. On assessment, the significant increase in the dichlorofluorescein (DCF) fluorescence, accumulation of 8-Oxo-2′-deoxyguanosine (8-oxo-dG), and levels of nuclear factor erythroid 2–related factor 2 (Nrf-2) strongly indicated the ability of the leachate to induce a pro-oxidant state inside the cell. The decrease in the mitochondrial membrane potential and alterations in the mitochondrial genome observed in leachate-exposed cells further suggested the disturbances in mitochondrial machinery. Moreover, these mitochondrial-associated redox imbalances were accompanied by the increased level of NF-κβ, pro-inflammatory cytokines, and DNA damage. In addition, the higher DNA fragmentation, release of nucleosomes, levels of polyadenosine diphosphate ADP-ribose polymerase (PARP), and activity of caspase-3 suggested the involvement of mitochondrial mediated apoptosis in leachate exposed cells. These observations were accompanied by the low proliferative index of the exposed cells. Conclusively, our results clearly indicate the ability of landfill leachate to disturb mitochondrial redox homeostasis, which might be a probable source for the immunotoxic consequences leading to plausible patho-physiological conditions in humans susceptible to such environmental exposures.

Potential toxicity of leachate from the municipal landfill in view of the possibility of their migration to the environment through infiltration into groundwater

“…Melanoma cells, as cancerous cells, are more resistant to oxidative stress and their proliferation rate is enhanced through the activity of ROS. The literature data point to the fact of the induction of oxidative stress in human cells by leachate (Gupta et al 2019 ).…”

Mapping the Mitochondrial Regulation of Epigenetic Modifications in Association With Carcinogenic and Noncarcinogenic Polycyclic Aromatic Hydrocarbon Exposure

“…Previously, we have reported that exposure to different environmental toxins including air pollutants considerably affects mitochondrial redox machinery. 22,23 In the present study, we investigated the mitochondrial-mediated epigenetic regulation in peripheral lymphocytes following exposure to a carcinogenic (BaP) and noncarcinogenic (ANT) PAHs, an important class of air pollutant. Overall, our findings suggest that exposure to ANT induces mitochondrial toxicity with no significant epigenetic alteration, while BaP disturbs the redox machinery and initiates a cascade of aberrant epigenetic modifications that include changes in the expression of mitochondrial miRNAs, DNA hypomethylation, and modification in histone tails.…”

“…The mean fluorescence intensity of the cells was then analyzed through flow cytometry (Attune NxT). 22 For assessment of mitochondria-mediated apoptosis, caspase-3 activity was measured in cells using the caspase-3 apoptosis kit. Briefly, the cells were washed and fixed for 20 minutes on ice.…”

Molecular insights into mitoepigenetic stress response signaling in age-associated cardiovascular disease risk

“…The GAPDH was used as an internal control. Ct values were recorded, and fold change was calculated by using ddCt method [17].…”