Dibutyl phthalate-induced activation of ROS and ERK1/2 causes hepatic and renal damage in Kunming mice

Abstract

<jats:p> Dibutyl phthalate (DBP), a ubiquitous environmental contaminant, has been reported to be involved in hepatic and renal tissue damage. However, the role of DBP in oxidative stress and in extracellular signal-regulated kinase (ERK1/2) pathways remains unclear. To investigate the underlying mechanism, Kunming (KM) mice received daily doses of combinations of 50 mg/kg DBP, 50 mg/kg vitamin E (VitE), and 1 mg/kg PD98059 for 28 consecutive days. Any changes in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, as well as any histopathological alterations in tissues, were observed to assess oxidative stress. In addition, the levels of alanine aminotransferase, aspartate aminotransferase, and albumin in serum were used to evaluate liver function. The levels of creatinine and urea nitrogen in serum were measured to evaluate kidney function. We found that DBP significantly increased oxidative damage and the expression of phosphorylated ERK1/2. Furthermore, pretreatment with the ERK inhibitor PD98059 followed by the antioxidant VitE attenuated the levels of ROS, MDA, ERK1/2 phosphorylation, and DBP-mediated disorders, indicating that the oxidative stress and the ERK1/2 pathways are associated with DBP-induced hepatic and renal dysfunction in KM mice. </jats:p>

Evaluation of the protective effects of quercetin and gallic acid against oxidative toxicity in rat’s kidney and HEK-293 cells

“…Phthalate esters are ubiquitously present in several consumer products and are known to induce oxidative stress in experimental models [ 22 , 23 ]. This effect has been associated with tissue atrophy, impaired tissue antioxidant defence and nephrotoxicity in different experimental models [ [24] , [25] , [26] , [27] , [28] ].…”

Human Erythrocytes Exposed to Phthalates and Their Metabolites Alter Antioxidant Enzyme Activity and Hemoglobin Oxidation

“…Some researchers have suggested that, when present in adequate amounts, ROS act as signaling molecules by participating in signal transduction pathways and can induce changes in enzyme activity, apoptosis, and necrosis. Finally, this leads to pathological changes and organ dysfunction [ 35 , 64 , 65 ].…”

“…Similar changes of the same parameters have been observed in animals (earthworms, Danio rerio , mice, rats). These examples may indicate that these substances produce oxidative stress in various organisms [ 31 , 32 , 33 , 34 , 35 , 36 ].…”

Oxidative damage in the liver and kidney induced by dermal exposure to diisononyl phthalate in Balb/c mice

“…It produces synergistic or combined responses to different extracellular stimuli and is closely related to cell proliferation, differentiation, apoptosis, and other activities (Finkel, 2011). The liver and kidneys can eliminate excess ROS through their own antioxidants and antioxidant enzymes, so the body's oxidants and antioxidants are dynamically balanced under normal conditions (Cheng et al, 2019;Valko et al, 2007). However, when some exogenous chemicals act excessively, this may lead to the rapid production of ROS and an imbalance between oxidation and anti-oxidation in cells or tissues.…”