Physical Exercise Exacerbates Acute Kidney Injury Induced by LPS via Toll-Like Receptor 4

Abstract

Introduction: Lipopolysaccharide (LPS) is a systemic response-triggering endotoxin, which has the kidney as one of its first targets, thus causing acute injuries to this organ. Physical exercise is capable of promoting physiological alterations and modulating inflammatory responses in the infectious process through multiple parameters, including the toll-like receptor (TLR)-4 pathway, which is the main LPS signaling in sepsis. Additionally, previous studies have shown that physical exercise can be both a protector factor and an aggravating factor for some kidney diseases. This study aims at analyzing whether physical exercise before the induction of LPS endotoxemia can protect kidneys from acute kidney injury. Methods: C57BL/6J male mice, 12 weeks old, were distributed into four groups: (1) sedentary (control, N = 7); (2) sedentary + LPS ( N = 7); (3) trained ( N = 7); and (4) trained + LPS ( N = 7). In the training groups, the animals exercised 5×/week in a treadmill, 60 min/day, for 4 weeks (60% of max. velocity). Sepsis was induced in the training group by the application of a single dose of LPS (5 mg/kg i.p.). Sedentary animals received LPS on the same day, and the non-LPS groups received a saline solution instead. All animals were euthanized 24 h after the administration of LPS or saline. Results: The groups receiving LPS presented a significant increase in serum urea ( p < 0.0001) and creatinine ( p < 0.001) concentration and renal gene expression of inflammatory markers, such as tumor necrosis factor alpha and interleukin-6, as well as TLRs. In addition, LPS promoted a decrease in reduced glutathione. Compared to the sedentary + LPS group, trained + LPS showed overexpression of a gene related to kidney injury (NGAL, p < 0.01) and the protein levels of LPS receptor TLR-4 ( p < 0.01). Trained + LPS animals showed an expansion of the tubulointerstitial space in the kidney ( p < 0.05) and a decrease in the gene expression of hepatic AOAH ( p < 0.01), an enzyme involved in LPS clearance. Conclusion: In contrast to our hypothesis, training was unable to mitigate the renal inflammatory response caused by LPS. On the contrary, it seems to enhance injury by accentuating endotoxin-induced TLR-4 signaling. This effect could be partly due to the modulation of a hepatic enzyme that detoxifies LPS.

The Effects of Two Different Dietary Regimens During Exercise On Outcome of Experimental Acute Kidney Injury

“…It has been shown that regular moderate-intensity exercise before induction of diabetes partially reduces the progression of renal brosis by signi cantly reducing advanced glycation end products (AGE), which consequently reduces the production of TGF-β1 in mesangial, broblasts and tubular cells (64). The results of Húngaro et al (2020) study contradict the ndings of present study, as they reported that moderate-intensity endurance exercise for four weeks before AKI could not prevent in ammation (55). A reason for the increased expression of TGF-β1 is the increased expression of bronectin and type four collagen following kidney damage, which in turn causes the accumulation of extracellular matrix and the progression of brosis.…”

“…It has been shown that performing eight weeks of moderate-intensity endurance exercise before induction of diabetes improves GFR after injury and prevents a large decrease in GFR (54). Toyama et al (2010) reported that exercise for 12 weeks improves GFR in patients with CKD (55). Although the mechanism by which moderate-intensity exercise improves renal function is not well understood, there is evidence to suggest that better metabolic control, reduced oxidative stress, and increased nitric oxide (NO) production may play a role in this protective process (51,52).…”

Fasudil ameliorated liposaccharide-induced acute kidney injury in mice by inhibiting NLRP3

“…Lipopolysaccharide may easily cause significant damage to organs, leading to marked increases in the levels of inflammatory markers and impairment of kidney function, which are considered major causes of AKI [12][13][14]. Therefore, in this study, the impact of fasudil on AKI mice was determined with respect to levels of BUN, Cr and NLRP3 which are important indicators.…”

Bibliometric Study of Pain after Spinal Cord Injury

“…Pain after SCI manifests in many ways. More than 50% of patients with SCI suffered chronic pain within 1 year after SCI [ 6 ]. The presence of chronic pain seriously affects the patients' daily life and the social impact.…”