Biochemical and Molecular Bases of Lead-Induced Toxicity in Mammalian Systems and Possible Mitigations

Abstract

The effects of lead exposure on mammals are reported to be devastating. Lead is present in all the abiotic environmental components such as brass, dust, plumbing fixtures, soil, water, and lead mixed imported products. Its continuous use for several industrial and domestic purposes has caused a rise in its levels, thereby posing serious threats to human health. The mechanisms involved in lead-induced toxicity primarily include free-radical-mediated generation of oxidative stress which directly imbalances the prooxidants and the antioxidants in body. The toxicity of lead involves damage primarily to major biomolecules (lipid, protein, and nucleic acids) and liver (hepatotoxicity), nervous system (neurotoxicity), kidney (nephrotoxicity) and DNA (genotoxicity), present in animals and humans. The activation of c-Jun NH2-terminal kinase, phosphoinositide 3-kinase, or Akt and p38 mitogen activated protein kinase signaling pathways are important for lead cytotoxicity. Lead increased apoptosis through signaling cascade and associated factors and significantly impairs cell differentiation and maturation. In addition, lead has great impact on metabolic pathways such as heme synthesis, thereby leading to the onset of anemia in lead exposed people. This review encompasses an updated account of varied aspects of lead-induced oxidative stress and the biomolecular consequences such as perturbations in physiological processes, apoptosis, carcinogenesis, hormonal imbalance, loss of vision, and reduced fertility and their possible remediation through synthetic (chelators) and natural compounds (plant-based principles). This paper is primarily concerned with the biomedical implications of lead-induced generation of free radical and the toxicity management in the mammalian system.

The effect of ellagic acid on spinal cord and sciatica function in a mice model of multiple sclerosis

“…Several plant extracts [ 49–51 ] are known to have antioxidant properties against oxidative stress in different organs and xenobiotics. [ 52–56 ] The results showed that lipid peroxidation and MDA level in the spinal cord tissue increased in Cup group and EA 100 mg/kg co‐treatment with Cup reversed this undesirable alteration compare with Cup group. Increased ROS production, oxidative phosphorylation dysfunction, and calcium hemostasis imbalance and decreased antioxidant defense system in serum and cerebrospinal fluid were reported in MS disease.…”

A Study on Redox Potential of Phytochemicals and their Impact on DNA

“…There was no effect of the solvent on human DNA. Lane [15]. The results of the present in vitro study indicated that the extracts of leaves of T. peruviana and A. mexicana were causing damage to DNA isolated from different living systems whereas C. limon was able to protect the DNA from damage in the concentration dependent manner.…”

Third‐Generation Solar Cells: Toxicity and Risk of Exposure

“…Calcium homeostasis is crucial for cell survival, [91] and lead binds to calcium-activated proteins with higher affinity than calcium itself. The neurotoxic effects of lead are connected to this ability to substitute calcium in biological functions and interfere with ion channels and pumps, [92] which is also the how lead passes through the blood brain barrier. [93] Lead affects the CNS and gives lower IQ, behavioral changes and learning deficits.…”