Early kidney damage induced by subchronic exposure to PM2.5 in rats

Abstract

BackgroundParticulate matter exposure is associated with respiratory and cardiovascular system dysfunction. Recently, we demonstrated that fine particles, also named PM2.5, modify the expression of some components of the angiotensin and bradykinin systems, which are involved in lung, cardiac and renal regulation. The endocrine kidney function is associated with the regulation of angiotensin and bradykinin, and it can suffer damage even as a consequence of minor alterations of these systems. We hypothesized that exposure to PM2.5 can contribute to early kidney damage as a consequence of an angiotensin/bradykinin system imbalance, oxidative stress and/or inflammation.ResultsAfter acute and subchronic exposure to PM2.5, lung damage was confirmed by increased bronchoalveolar lavage fluid (BALF) differential cell counts and a decrease of surfactant protein-A levels. We observed a statistically significant increment in median blood pressure, urine volume and water consumption after PM2.5 exposure. Moreover, increases in the levels of early kidney damage markers were observed after subchronic PM2.5 exposure: the most sensitive markers, β-2-microglobulin and cystatin-C, increased during the first, second, sixth and eighth weeks of exposure. In addition, a reduction in the levels of specific cytokines (IL-1β, IL-6, TNF-α, IL-4, IL-10, INF-γ, IL-17a, MIP-2 and RANTES), and up-regulated angiotensin and bradykinin system markers and indicators of a depleted antioxidant response, were also observed. All of these effects are in concurrence with the presence of renal histological lesions and an early pro-fibrotic state.ConclusionSubchronic exposure to PM2.5 induced an early kidney damage response that involved the angiotensin/bradykinin systems as well as antioxidant and immune imbalance. Our study demonstrates that PM2.5 can induce a systemic imbalance that not only affects the cardiovascular system, but also affects the kidney, which may also overall contribute to PM-related diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0179-8) contains supplementary material, which is available to authorized users.

The activation of antioxidant and apoptosis pathways involved in damage of human proximal tubule epithelial cells by PM2.5 exposure

“…Kidney injury molecule-1 (KIM-1) is a type l transmembrane glycoprotein and potential biomarker for the detection of tubular injury in renal diseases [40]. It was reported that the expression of KIM-1 protein in the kidney cortex of the PM 2.5 -exposed group was fourfold higher than those of the control group in SD rats induced by PM 2.5 exposure during the early kidney injury [8]. Our present study showed that exposure to PM 2.5 induced significant increases in the levels of KIM-1 in both a dose-and time-dependent manner, which is indicative of injury to the proximal tubule epithelium.…”

“…Recently, some epidemiological studies have reported a strong and consistent association between PM 2.5 exposure and reduced kidney function as well as an increased rate of renal function decline [5][6][7]. Studies have also shown that mid-/long-term exposure to high levels of PM 2.5 can induce kidney damage in rodents [8,9]. However, the mechanism of PM 2.5 -induced renal dysfunction remains unclear.…”

PM2.5 exposure induced renal injury via the activation of the autophagic pathway in the rat and HK-2 cell

“…The strong correlation between chronic kidney disease and cardiovascular disease has been demonstrated by both observational studies and a meta-analysis (Moody et al, 2012). In conditions of renal insu ciency and in patients undergoing dialysis is prone to cardiovascular diseases have been reported in clinical practice, which indicates a potential interaction between the kidney and the cardiovascular system (Aztatzi-Aguilar et al, 2016). Tavera Busso et al observed more severe alterations of brosis, mesangial expansion, tubular epithelial cells detachment, decrease glomerular and tubular lumen volumes in a spontaneously hypertensive rat (SHR) model after sub-chronic exposure to PM 2.5 than healthy animals (Tavera Busso et al, 2018).…”

“…Bowe et al estimated that the global burden of incident chronic kidney disease (CKD) attributable to PM 2.5 was about 6.95 million in 2016, and air pollution may be an important risk factor for the prevalence of kidney disease (Bowe et al, 2019). Experimental studies have also shown that mid-/long-term exposure to high levels of PM 2.5 can induce kidney damage in rodent models (Aztatzi-Aguilar et al, 2016;Ge et al, 2018).…”

Spatial distribution of kidney disease in the contaminated site of Taranto (Italy)

“…In fact, a number of epidemiological studies have shown an association between exposure to cadmium and adverse kidney outcomes . With regard to PM2.5, recent experimental and epidemiological studies have provided evidence that PM2.5 exposure is associated with decreased kidney function, and high rate of kidney disease …”