Вплив модуляторів циркадіанного ритму на екскреторну та натрійрегулювальну функцію нирок щурів за умов гострого десинхронозу та ліпополісахарид-індукованої системної запальної відповіді

O.  Gutnik; V. Kostenko; O.  Silkova; D.  Khmil

doi:10.31450/ukrjnd.2(82).2024.08

O. Gutnik Poltava State Medical University, Poltava, Ukraine https://orcid.org/0009-0007-1198-5158
V. Kostenko Poltava State Medical University, Poltava, Ukraine https://orcid.org/0000-0002-3965-1826
O. Silkova Poltava State Medical University, Poltava, Ukraine https://orcid.org/0000-0002-2605-204X
D. Khmil Poltava State Medical University, Poltava, Ukraine https://orcid.org/0000-0002-1003-455X

DOI: https://doi.org/10.31450/ukrjnd.2(82).2024.08

Keywords: kidney function, acute desynchronosis, lipopolysaccharide-induced systemic inflammatory response, sodium glutamate, melatonin, quercetin

Abstract

The present study aims to investigate the effect of circadian rhythm modulators (sodium glutamate, melatonin, and quercetin) on the excretory and sodium-regulating function of the kidneys in rats during acute desynchronosis (AD) and lipopolysaccharide (LPS)-induced systemic inflammatory response (SIR).

Methods. Forty-nine white male Wistar rats were randomly divided into seven groups, each consisting of seven animals: Group 1 served as the control; Group 2 comprised animals exposed to LPS-induced SIR; Group 3 involved rats exposed to AD; Group 4 included animals exposed to AD under LPS-induced SIR. The rats in Groups 5, 6, and 7 over the period of exposure to modeled AD during LPS-induced SVD received intragastrically (via a gavage tube) the following compounds daily before morning feeding: sodium glutamate in a dose of 20 mg/kg, melatonin in a dose of 5 mg/kg, and quercetin in a dose of 200 mg/kg, respectively. Serum concentrations of cortisol and the acute phase inflammatory protein ceruloplasmin were measured. Kidney functions were studied under conditions of induced diuresis.

Results. AD modeling during LPS-induced SIR increased the content of serum cortisol by 18.3% (P<0.001) compared with the results of group 3, elevated the concentration of ceruloplasmin by 12, 2% (P<0.001) relative to the value of group 2, lessened glomerular filtration rate (GFR) by 20.9% (P<0.01) and 17.1% (P<0.001), as well as decreased absolute sodium ion reabsorption by 24.2% and 23.4% (P<0.001) relative to the results of groups 2 and 3, respectively. The administration of sodium glutamate under the experimental conditions significantly worsened the changes in markers of acute stress and acute-phase response and resulted in the GFR intensification by 17.6% (P<0.01), and the reduction of absolute reabsorption of this ion by 19.7% (P<0.001) compared with the values of group 4. Melatonin and quercetin, on the contrary, reduced serum cortisol and ceruloplasmin concentrations, normalized induced diuresis and GFR, and increased absolute sodium reabsorption by 35.9 and 45.0% (P<0.001), respectively, compared with the findings of group 4.

Conclusions. Under experimental conditions, the administration of sodium glutamate significantly worsens the markers of acute stress and acute-phase response, GFR, and sodium reabsorption. Conversely, the use of exogenous melatonin and quercetin ameliorates the above-mentioned markers compared to the values following the AD modeling during LPS-induced SIR.