Renoprotective effect of oral rehydration solution III in exertional heatstroke rats

Abstract

Aim: Exertional heastroke (EHS) can lead to acute kidney injury. Oral rehydration solution III (ORS III), recommended by WHO in 2004, is used to rehydrate children with gastroenteritis. This study aimed to characterize the renoprotective effect of ORS III in EHS rats. Methods: Rats were randomly divided into Group Control, Group EHS, Group EHS þ Water, and Group EHS þ ORS. Thirty minutes before the experiment, ORS III was orally administrated to Group EHS þ ORS, Water was given to Group EHS þ Water. Rats from Group EHS, Group EHS þ Water and Group EHS þ ORS were then forced to run until they fatigued. Core temperature (Tc) was monitored and 40.5 C was considered as the onset of heatstroke. Serum creatinine (SCr), blood urea nitrogen (BUN) were measured using an automated biochemical analyzer. Serum neutrophil gelatinase-associated lipocalin (NGAL) was measured using an NGAL ELISA Kit. Light microscopy was used for kidney structural analysis. Results: SCr level in Group EHS was no different from Group Control (p > .05), while BUN and NGAL levels in Group EHS were higher than Group Control (p <.001, p < .001). SCr, BUN and NGAL concentrations in group EHS þ Water were no different from Group EHS (p > .05). SCr, BUN levels in Group EHS þ ORS were no different from Group EHS (p > .05). But NGAL levels were significant in these two groups (p ¼ .012). Renal histopathologies of rats in Group EHS and Group EHS þ Water showed flattened lumens filled with eosinophilic materials. The damage was milder in Group EHS þ ORS, in which injured tubules showed degeneration of the tubular epithelium and sloughing of the brush border membrane. Conclusion: ORS III could alleviate the kidney injury in EHS rats.

Biomarkers of heatstroke‐induced organ injury and repair

“…Recent findings support that the aetiology of kidney injury during heatstroke also includes injury to the renal tubules (Lin & Zhang, 2019). This study additionally identified serum neutrophil gelatinase-associated lipocalin (NGAL) as a potential early biomarker of kidney injury secondary to EHS, such that elevations in serum NGAL were almost 10 times higher post-EHS compared to a non-heated control group (Lin & Zhang, 2019). Such observations are consistent with findings in humans undertaking exercise in the heat (Schlader et al, 2017).…”

“…This likely occurs secondarily to the heatstroke-induced systemic inflammation and coagulation activation that catalyse haemorrhagic and thrombotic events within the kidneys (and other organs), similar to sepsis (Ma et al, 2019). Recent findings support that the aetiology of kidney injury during heatstroke also includes injury to the renal tubules (Lin & Zhang, 2019). This study additionally identified serum neutrophil gelatinase-associated lipocalin (NGAL) as a potential early biomarker of kidney injury secondary to EHS, such that elevations in serum NGAL were almost 10 times higher post-EHS compared to a non-heated control group (Lin & Zhang, 2019).…”

The Gastrointestinal Exertional Heat Stroke Paradigm: Pathophysiology, Assessment, Severity, Aetiology and Nutritional Countermeasures

“…To date, no published animal research has attempted to evaluate the role of GI MT on EHS pathophysiology. Inconsistent with EHS GI paradigm, recent data demonstrate the pattern of cytokine response during EHS to be largely inconsistent to those displayed following GI microbial PAMP recognition (e.g., minimal TNF-α/IL-1β response; [60]. With this is mind, it is plausible that cytokine production initiated in response multiple organ injury (e.g., skeletal muscle; [61]) performs a greater role in EHS pathophysiology than previously proposed [37,47].…”

“…Similarly, direct intravenous endotoxin injection prior to sub-lethal CHS in rodents (peak T core =~42-43 • C) unexpectedly led to fatalities in 40% of animals (versus 0% in controls; [57]), or best-case increased symptoms of multiple-organ injury [58]. At present, only one study has assessed the role of GI barrier integrity utilising a relevant EHS model, whereby rats run to thermal collapse in the heat (T core = 40.5-42.5 • C) displayed significant histopathological damage to all GI segments [59,60], together with a significant pro-inflammatory response [61]. However, in comparison to CHS models with a similar clinical endpoint (peak T core =~42-42.5 • C), the magnitude of GI barrier integrity loss was lower following EHS, though this finding is potentially attributable to ã 50% lower thermal area [60].…”

“…At present, only one study has assessed the role of GI barrier integrity utilising a relevant EHS model, whereby rats run to thermal collapse in the heat (T core = 40.5-42.5 • C) displayed significant histopathological damage to all GI segments [59,60], together with a significant pro-inflammatory response [61]. However, in comparison to CHS models with a similar clinical endpoint (peak T core =~42-42.5 • C), the magnitude of GI barrier integrity loss was lower following EHS, though this finding is potentially attributable to ã 50% lower thermal area [60]. To date, no published animal research has attempted to evaluate the role of GI MT on EHS pathophysiology.…”