Biological Consequences of Vanadium Effects on Formation of Reactive Oxygen Species and Lipid Peroxidation

Abstract

Lipid peroxidation (LPO), a process that affects human health, can be induced by exposure to vanadium salts and compounds. LPO is often exacerbated by oxidation stress, with some forms of vanadium providing protective effects. The LPO reaction involves the oxidation of the alkene bonds, primarily in polyunsaturated fatty acids, in a chain reaction to form radical and reactive oxygen species (ROS). LPO reactions typically affect cellular membranes through direct effects on membrane structure and function as well as impacting other cellular functions due to increases in ROS. Although LPO effects on mitochondrial function have been studied in detail, other cellular components and organelles are affected. Because vanadium salts and complexes can induce ROS formation both directly and indirectly, the study of LPO arising from increased ROS should include investigations of both processes. This is made more challenging by the range of vanadium species that exist under physiological conditions and the diverse effects of these species. Thus, complex vanadium chemistry requires speciation studies of vanadium to evaluate the direct and indirect effects of the various species that are present during vanadium exposure. Undoubtedly, speciation is important in assessing how vanadium exerts effects in biological systems and is likely the underlying cause for some of the beneficial effects reported in cancerous, diabetic, neurodegenerative conditions and other diseased tissues impacted by LPO processes. Speciation of vanadium, together with investigations of ROS and LPO, should be considered in future biological studies evaluating vanadium effects on the formation of ROS and on LPO in cells, tissues, and organisms as discussed in this review.

Substitution Kinetics, Albumin and Transferrin Affinities, and Hypoxia All Affect the Biological Activities of Anticancer Vanadium(V) Complexes

“…Hypoxic conditions of solid cancer tumors, caused by poor blood supply, significantly complicate cancer chemotherapy, and a consideration of compounds that remain active under such conditions is of interest for drug discovery . Anticancer activities of V complexes are expected to decrease under low oxygen conditions due to both the increased resilience of cancer cells and the likely involvement of ROS in the anticancer activity of V complexes. ,, For instance, a complete loss of in vitro anticancer activity was demonstrated for V­(IV) complexes with carbohydrate ligands under hypoxic conditions (1% O 2 ) . The proliferation of MDA-MB-231 cells under hypoxic conditions in the presence or absence of 5.0 μM fresh or aged 1 or 2 was followed using an IncuCyte Zoom instrument that was placed inside a hypoxic chamber (1% O 2 , 5% CO 2 , and 94% N 2 ) at 310 K (Figure d).…”

“…18−22 In addition, vanadate in the presence of hydrogen peroxide can form peroxido vanadates or other vanadium species involved in the reactive oxygen species (ROS)-related regulation of cell signaling. 19,23,24 A promising recent application is the use of inorganic V(V/IV) salts and V(V) complexes with organic ligands as potentiators of oncolytic viruses, 25−27 which are used for immunotherapy of advanced cancers. 27,28 Despite decades of research, the clinical use of V(V/IV) complexes has been hampered by their extensive and elaborate reactivities in biological media, including hydrolysis, redox reactions, binding to proteins and other biomolecules, involvement in ROS processes, and interactions with metabolites.…”

“…A wide range of biological activities, including anticancer, antimicrobial, antidiabetic, and tissue-regenerating properties, have been reported for structurally diverse V­(V/IV) complexes. − This diversity also allows a wide range of cancers that can be effected and potentially treated by these compounds. ,, Although the active species have rarely been identified, the effects of a significant number of complexes have been attributed to their decomposition in biological environments with the formation of V­(V) or V­(IV) oxido species, ,− which can act as potent phosphatase inhibitors. ,− Vanadate is known to inhibit all phosphorylase enzymes, and the inhibition of protein tyrosine phosphatases is particularly noteworthy considering their roles in signal transduction and regulation. − In addition, vanadate in the presence of hydrogen peroxide can form peroxido vanadates or other vanadium species involved in the reactive oxygen species (ROS)-related regulation of cell signaling. ,, A promising recent application is the use of inorganic V­(V/IV) salts and V­(V) complexes with organic ligands as potentiators of oncolytic viruses, − which are used for immunotherapy of advanced cancers. , …”

Vanadium Complexes with Thioanilidine Derivatives of Aminoacids: Inhibition of Human Phosphatases and Cell-Type Specificity in Various Models of Metabolic Disturbances

“…This may intensify oxidative stress, which is an important mechanism of hepatocyte steatosis. Vanadium compounds may have a pro-oxidative effect, depending on the degree of oxidation or the presence of other ligands, which may lead to lipid peroxidation in the liver [113,114]. The accumulation of lipids observed under the influence of some ONO complexes may also result from the stimulation of glucose transport and the intensification of lipid synthesis in the hepatocytes.…”

A study of the antioxidant properties of Keggin-type polyoxometalates

“…Scholars at home and abroad have been actively screening for effective substances with scavenging effects on oxygen radicals and inhibiting functions on lipid peroxidation. 31,32 However, the majority of the literature on the biological activity of POMs has comprised in vitro studies, while there is a relative lack of data on in vivo studies related to the toxicity of these compounds. 33 Thus, the discovery of new antioxidants has become an effective way to treat various free radical-related diseases.…”