The nephrotoxicity risk in rats subjected to heavy muscle activity

When the body is exposed to insults, the kidneys exhibit adaptive changes termed renal cytoresistance, characterized by cholesterol accumulation in the membranes of the tubule cells. However, heavy muscle activity has not yet been accepted as one of the stressors that could lead to cytoresistance. In order to study the renal functional characteristics of animals exposed to heavy muscle activity, rats were subjected to exhaustive treadmill exercise for 5 days and their data was compared to those of sedentary controls. It was found that in exercised rats, blood lactate, muscle citrate synthase and proximal tubule peroxynitrite levels were all elevated, suggesting the presence of oxidative stress in the proximal tubule segments. However, mean arterial pressure, renal blood flow, glomerular filtration rate, fractional excretion of sodium and potassium, and organic anion excretion remained normal. Despite unchanged blood cholesterol levels, cholesterol loading in the proximal tubule segments, especially the free form, and decreased lactate dehydrogenase release from cytoresistant proximal tubule segments indicated the development of renal cytoresistance. However, this resistance did not seem to have protected the kidneys as expected because organic anion accumulation associated with glycosuria and proteinuria, in addition to the elevated urinary cholesterol levels, all imply the presence of an impaired glomerular permeability and reabsorption in the proximal tubule cells. Therefore, we suggest that in response to heavy muscle activity the tubular secretion may remain intact, although cytoresistance in the proximal tubule cells may affect the tubular reabsorptive functions and basolateral uptake of substances. Thus, this differential sensitivity in the cytoresistance should be taken into account during functional evaluation of the kidneys. Key pointsThe cholesterol loading and decreased LDH release from PTSs isolated from exhausted rats indicate the heavy muscle activity induced renal cytoresistance.Heavy muscle activity-induced renal cytoresistance did not preserve the kidney functions.Organic anion accumulation as well as failure in the absorptive capacity of the tubule cells suggest the presence of some biochemical changes and elevated vulnerability of kidneys against nephrotoxic agents in rats subjected to heavy muscle activity.