**1. Introduction**

Various events can strain the human body, putting stress on the cells and tissues. Oxidative stress, heat shock, hypersensitivity, autoimmune diseases and other disorders can cause cell dysfunction and lead to apoptosis [1]. Besides passive release, dying cells produce an increased amount of uric acid (UA), which can indicate both the environmental and medical conditions that induce cell damage [2]. DAMPs are molecules that have a physiological role inside the cell but acquire additional functions when released from the cells: they alert the body about danger, stimulate an inflammatory response, and promote the regeneration process [3]. Apart from their passive release by dead cells, some DAMPs can be secreted or exposed by living cells undergoing life-threatening stress.

Uric acid, being a final product of purine metabolism, has a high impact on human health. It is produced in the liver, intestines, kidneys, vascular endothelium, and muscles by the metabolism of purine [2].

**Citation:** Kneževi´c, S.; Ognjanovi´c, M.; Stankovi´c, V.; Zlatanova, M.; Neši´c, A.; Gavrovi´c-Jankulovi´c, M.; Stankovi´c, D. La(OH)3 Multi-Walled Carbon Nanotube/Carbon Paste-Based Sensing Approach for the Detection of Uric Acid—A Product of Environmentally Stressed Cells. *Biosensors* **2022**, *12*, 705. https://doi.org/10.3390/ bios12090705

Received: 25 July 2022 Accepted: 24 August 2022 Published: 1 September 2022

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Both high and low human plasma UA concentrations can indicate a pathological state. On the one hand, UA acts as a scavenger of peroxyl radicals, hydroxyl radicals, and singlet oxygen, thus exhibiting antioxidative features. It is a specific inhibitor of radicals generated by the decomposition of peroxynitrite, preventing cell injuries and nitration of tyrosine residues in proteins. Furthermore, it can protect against oxidative damage by chelating metal ions such as iron and copper, lowering their catalytic activity in free-radical reactions [4]. UA also shows neuroprotective properties and reduces the risk of multiple sclerosis, Parkinson's disease, Alzheimer's disease, and optic neuritis [5].

UA also acts as an initiator and amplifier of allergic inflammation and can cause hypertension and cardiovascular diseases via the induction of growth factors, hormones, cytokines, and autacoids. UA penetrates vascular smooth muscle fibers and activates signal transduction, increasing the expression of inflammatory mediators. Furthermore, urate crystals can deposit in the connective tissues of the joints, tendons, kidneys, and rarely in heart valves and the pericardium. Consequently, UA is a risk factor for renal disorders (kidney injuries and kidney stones), acute and chronic inflammatory arthritis, gout, myocardial infarction, and stroke [2,5]. Elevated serum uric acid levels are associated with insulin resistance and diabetes mellitus [2].

The important UA feature is that it is produced in higher concentrations when the cells suffer from stress. Both live and dying cells degrade their nucleic acids in deamination and dephosphorylation processes. Purine nucleoside phosphorylase converts the relevant degradation products, inosine and guanosine, to the purine bases, hypoxanthine and guanine, which further metabolize to xanthine. Oxidation of xanthine via xanthine oxidase leads to the formation of UA. Therefore, although uric acid is regularly present in cells, it increases in concentration when the cells are damaged [2]. The UA's release from dying cells can serve as an indicator of unfavorable environmental factors or pathological states.

Considering its importance and abundance in the human body, it is no wonder that numerous methods have been developed for UA detection and determination. The separation and detection methods commonly involve chromatography or electrophoresis coupled with UV/VIS [6–10] spectroscopy or electrochemical detection (voltammetry [11–16], ECL [17–20], and amperometry [21–25]), including both enzymatic and nonenzymatic approaches [26]. Recently, attention has shifted toward electrochemical sensors and biosensors because they enable the fast, direct, and precise determination of the analyte in the complex biological matrix.

Enzyme-based UA biosensors use uricase as an enzyme for the oxidation of uric acid [27,28]. The enzyme-based approach is expensive, and the obtained sensor is sensitive to environmental conditions, lacks reproducibility, and requires complicated immobilization of the enzyme. Non-expensive and robust non-enzymatic sensors perform direct oxidation of UA on the surface of the electrode material [29,30]. Various materials, such as covalent organic and metal incorporated conductive polymers [13,16,19,23], metal oxides [30–32], carbon-based materials, and their composites [11,12,33], have been tested for UA detection [5,26]. These nanomaterials have been recognized as promising materials for the development of analytical methods for the detection not only of UA but also of numerous other biologically active compounds [34–37].

The use of La [32,38,39]-based electrode materials has been reported in the literature with the main applications in fuel cells [40–42] and sensing devices [43–46], while Wang et al. [47] used LaFeO**<sup>3</sup>** for the simultaneous determination of dopamine, uric acid and ascorbic acid, thus proving the materials' compatibility with these analytes. La doping can affect lattice structures and phase transformations of compounds due to its larger atomic radius and unique electron structure, thus enhancing the catalytic and electrochemical properties of La-doped materials [32]. Furthermore, Guo et al. [48] suggested that the alkaline properties of La(OH)**<sup>3</sup>** contribute to the acidic analytes' bonding. To improve the conductivity and increase the active surface and electron transfer of the electrode, lanthanum hydroxide was incorporated into the composite with multi-walled

carbon nanotubes (MWCNTs), which possess exceptional mechanical and physicochemical properties [38,49].

This study aims to develop an electrochemical sensor for the fast, accurate, and precise measurement of UA released from damaged cells, or rather for monitoring the dependence between environmental factors and the stress they cause to the cells/tissues (Scheme 1). An electrochemical sensor was developed using a glassy carbon paste electrode modified with newly synthesized nanomaterial consisting of MWCNTs decorated with La(OH)**3**. The obtained sensor was used for the amperometric detection of uric acid under optimal experimental conditions. Furthermore, the influence of common interfering substances on UA determination was examined, as well as the reproducibility, repeatability, and stability of the proposed sensor. We showed that the proposed method could be used to evaluate stress factors in medical research and clinical practice.

**Scheme 1.** Idea of the work.
