Salivary biomarkers of oxidative stress in children with dental caries: Systematic review and meta-analysis

Highlights

• Biomarkers of salivary oxidative stress are influenced by dental caries.

• Antioxidant systems are increased in children affected by dental caries.

• Biomarkers of oxidative damage are reduced in saliva of children with dental caries.

• Salivary parameters are reduced in children with caries lesions.

Abstract

Objective

To assess the relationship between salivary biomarkers of oxidative stress and dental caries in children.

Methods

Studies conducted in children up to 12 years old comparing salivary biomarkers of oxidative stress such as malondialdehyde (MDA), superoxide dismutase (SOD), uric acid, and total antioxidant capacity (TAC), considering children with dental caries lesions and caries-free ones were selected. In addition, salivary parameters such as salivary flow, pH, buffering capacity, calcium and total protein levels were evaluated. A systematic literature review was carried out in 8 databases. The standardized mean difference (SMD) was measured using inverse variance as a statistical method and random effects as an analysis model, corresponding to a 95% confidence interval (CI).

Results

The TAC levels were higher in children affected by dental caries compared to caries-free ones (control group), regardless of age (SMD 2.66, CI 1.33, 3.98), or gender (SMD 0.98, CI 0.56, 1.39). When adjusted for normalized protein, MDA levels were lower in the dental caries group than in the control group (SMD −16.51, CI −29.02, −4.00), and SOD levels were higher in the dental caries group (SMD 5.09, CI 0.01.10.18). The total protein concentration in saliva of children with dental caries was higher than in the control group, regardless of age (SMD 0.98, CI 0.27, 1.69), or gender (SMD 0.77, CI 0.45, 1.10). The salivary parameters assessed had lower levels in children affected by dental caries (p < 0.05).

Conclusions

The levels of oxidative stress biomarkers and salivary parameters are altered in saliva of children with dental caries.

Introduction

The evaluation of salivary biomarkers of oxidative stress has been used for the diagnosis of several diseases in the oral cavity of children (Araujo, Nakamune, Garcia, Pessan, & Antoniali, 2020; Buczko, Zalewska, & Szarmach, 2015; Darczuk et al., 2016; Silva, Troiano, Nakamune, Pessan, & Antoniali, 2016), since they may be involved in the onset and/or development of biofilm-mediated diseases, such as dental caries (Mahjoub, Ghasempour, Gharage, Bijani, & Masrourroudsari, 2014). In addition, saliva collection is characterized as a non-invasive, straightforward, safe, inexpensive, fast and painless method (Hassaneen & Maron, 2017).

Oxidative damage is a consequence of oxidative stress, which is defined by the increased concentration of reactive oxygen and nitrogen species, associated or not with the reduced activity of antioxidant systems (Betteridge, 2000). Among main markers of oxidative damage are malondialdehyde (MDA), as a stable end product of membrane lipid peroxidation, and 8-hydroxy-desoxguanosine (8-Hodgkins) (Jurczak et al., 2017). In fact, antioxidant systems are highly complex, having as an important function the protection against the effects of reactive oxygen species (ROS) (Pyati, Naveen Kumar, Kumar, Praveen Kumar, & Parveen Reddy, 2018; Tulunoglui, Demirtas, & Tulunoglu, 2006). Salivary antioxidant systems can be classified as enzymatic and non-enzymatic (Jurczak et al., 2017). Glutathione peroxidase, catalase and superoxide dismutase (SOD) are examples of enzymatic systems, with SOD being the main antioxidant enzyme (Jurczak et al., 2017). In contrast, the non-enzymatic antioxidant system includes the uric acid and the glutathione, which together make up the total antioxidant capacity (TAC) (Battino, Ferreiro, Gallardo, Newman, & Bullon, 2002).

Studies have shown a unique behavior regarding salivary antioxidant response to oxidative stress in children with dental caries, with increased TAC and SOD levels in this group when compared to caries-free children, in an environment where MDA is decreased (Araujo et al., 2020; Silva et al., 2016). On the other hand, other studies suggest no differences in biomarker levels between children with and without the disease (Subramanyam et al., 2018, Tulunoglui et al., 2006). In view of the conflicting evidence described above, the present systematic review with meta-analysis aimed to assess the relationship between salivary biomarker levels related to oxidative stress, as well as salivary parameters related to dental caries in children with or without dental caries. The question review was structured as follows: Could salivary biomarkers associated with oxidative stress be altered in saliva of children with dental caries?