Multimetal exposure: Challenges in diagnostics, prevention, and treatment.

Extensive use of heavy metals has posed a serious concern for ecosystem and human too. Heavy metals are toxic in nature and their accumulation in human body causes serious disorders such as neurological disease, cardiac disease, gastrointestinal problems, skin disorders, reproductive disease, lungs diseases, and so on. Furthermore, heavy metals not only affect the human health but also have a negative impact on the economy. In the current review, we have elaborated the impact of heavy metal exposure on human health and socioeconomics. We have discussed the molecular mechanism involved in the heavy metal-induced human disorders such as oxidative stress, neuroinflammation, and protein misfolding. Finally, we discussed the preventive measure and treatment strategy that could counter the negative effects of heavy metal intoxications. In conclusion, there is a substantial correlation between heavy metals and the onset and advancement of several health issues. Chelation treatment could be a useful tactic to lessen the toxic metal load and the difficulties that come with it.

Albumin-Based Nanocarriers for the Simultaneous Delivery of Antioxidant Gene and Phytochemical to Combat Oxidative Stress.

Human serum albumin (HSA) nanoparticles are promising biocompatible, nontoxic, and non-immunogenic platforms for biomedical applications such as bioimaging and drug and gene delivery. The development of nonviral gene delivery vectors is a great challenge for efficient and safe gene therapy. Sulforaphane (SF) can stimulate the expression of antioxidant genes via activation of a nuclear transcription factor, the erythroid-2 related factor 2 (Nrf-2). Here, we use polyethyleneimine (PEI)-stabilized HSA nanoparticles to stimulate endogenous antioxidant defense mechanisms in lung epithelial cells L-132 through the combinatorial effect of SF drug and antioxidant superoxide dismutase 1 gene (pSOD1 plasmid) delivered by HSA-PEI-SF-pSOD1 nanocomposites (NCs). The developed NCs demonstrated high biocompatibility (L-132 viability, >95%, MTT assay) and high antioxidant activity because of efficient entry of the SOD1 gene and SF-loaded NCs at a very low (3 µg) dose in L-132 cells. A high transfection efficiency of L-132 cells (∼66%, fluorescent microscopy) was obtained with the GFP-tagged transgene SOD1-GFP. We speculate that the antioxidant activity of HSA-PEI-SF-pSOD1 NCs in L-132 cells is due to the initial release of SF followed by subsequent SOD1 gene expression after three to four days of incubation. Hence, the developed HSA-based NCs can be efficient biocompatible nanocarriers for safe and effective drug and gene delivery applications to treat diseases with high oxidative stress due to combinatorial SF and SOD1 gene mechanisms.

Alpha-Lipoic Acid Protects Co-Exposure to Lead and Zinc Oxide Nanoparticles Induced Neuro, Immuno and Male Reproductive Toxicity in Rats.

We evaluated the neuro-, immuno-, and male reproductive toxicity of zinc oxide nanoparticles (ZnO NPs) alone and in combination with lead acetate. We also studied the therapeutic role of α-lipoic acid postexposure. Lead (10 mg/kg, body weight), ZnO NPs (100 mg/kg, bwt) alone, and their combination were administered orally in Wistar rats for 28 days, followed by the administration of α-lipoic acid (15 mg/kg, bwt) for the next 15 days. Our results demonstrated protective effects of α-lipoic acid on lead and ZnO NP-induced biochemical alterations in neurological, immunological, and male reproductive organs in rats. The altered levels of blood δ-aminolevulinic acid dehydratase (ALAD), immunoglobulins (IgA, IgG, IgM, and IgE), interleukins (IL-1ß, IL-4, and IL-6), caspase-3, and tumor necrosis factor (TNF-α) were attenuated by lipoic acid treatment. Lead and ZnO NP-induced oxidative stress was decreased by lipoic acid treatment, while a moderate recovery in the normal histoarchitecture of the brain section (cortex and hippocampus) and testes further confirmed the neuro- and male reproductive toxicity of lead and ZnO NPs. We also observed a significant decrease in the blood metal content in the animals treated with lipoic acid compared to the lead-administered group, indicating the moderate chelating property of lipoic acid. It may thus be concluded that lipoic acid might be a promising protective agent against lead and ZnO NP-induced alterations in the neurological, immunological, and reproductive parameters.