A mouse model of exertional heatstroke-related acute kidney injury

Abstract

Background: Acute kidney injury (AKI) is a common complication of exertional heat stroke (EHS) with a complex pathogenesis. We established a stable mouse model of EHS-related AKI (EHS-AKI).Methods: C57BL/6 male mice were divided into 6 groups: Saline Control group, Glycerol Control group, Saline + Sham heat exercise (SHE) group, Saline + Heat exercise (HE) group, Glycerol + SHE group, and Glycerol + HE group. Samples from the Saline Control group and the Glycerol Control group were taken 6 h after the intramuscular injection of saline (4 mL/kg) or glycerol (4 mL/kg) to provide a baseline for comparisons with the other 4 groups. The other 4 groups of mice started exercise 6 h after the intramuscular injection of saline or glycerol, and were sacrificed to collect samples after exercise. Finally, serum and the pathology of kidney and muscle tissues were quantified.Results: There were no differences in the creatinine (Cr), blood urea nitrogen (BUN), creatine kinase (CK), and myoglobin (MYO) levels, but the interleukin 6 (IL-6) level was more increased (P<0.05) in the Glycerol Control group than the Saline Control group at the baseline. The IL-6 levels of the Glycerol + HE group were also higher than those of the Saline + HE groups at 6 and 12 h (P<0.05). The Cr levels at 12 h and 1 day, the BUN levels at 6 h, 12 h, 1 day, and 2 days in the Glycerol+ HE group were higher than the baseline levels (P<0.05). And the renal pathological scores at 6 h, 12 h, 1 day, 2 days, or 3 days were 0.79, 1.29, 1.58, 0.85, and 0.77. However, there was only slight renal pathological injury in the Saline + HE group at 12 h, and 1 day, and the scores were 0.13, and 0.41. The CK level in each group all peaked at 6 h after exercise and higher than the baseline (P<0.05). However, there was no difference in the MYO levels of each group compared to the baseline. Conclusions:We established a stable mouse model of EHS-AKI by conducting a heat exercise after the intramuscular injection of glycerol. Our findings lay the foundation for follow-up clinical and basic research.

Molecular Challenges and Opportunities in Climate Change-Induced Kidney Diseases

“…As priorly discussed, there is evidence from both animal and human studies that shows that exposure to high temperatures can induce cellular stress in several organs including the kidneys [ 20 , 90 , 91 ]. In this regard, stress is one of the principal factors that trigger protein unfolding, misfolding and/or aggregation, which causes a response that mainly leads to the induction of certain gene transcriptions of proteins [ 92 ].…”

ZBP1 and heatstroke

“…These factors lead to intestinal ischemia, which induces the generation of intestinal free radicals and intestinal mucosal edema and increases intestinal permeability, all of which promote intestinal disruption and lead to the release of a large number of intestinal toxins into the blood circulation (13,109,(151)(152)(153)(154)(155)(156)(157)(158). Renal failure is a common complication of heatstroke that is mainly manifested as tubular necrotizing acute renal failure and can be caused by massive protein deposition in the renal tubular epithelial cells after hemolysis and rhabdomyolysis (13,21,(158)(159)(160)(161)(162)(163)(164)(165)(166). Liver dysfunction in patients with heatstroke and in animal models is considerably common, with the liver injury mainly occurring in the recovery period of heatstroke (167)(168)(169)(170)(171)(172)(173)(174).…”