Browsing by Author "Nesovic Ostojic, Jelena (15060276300)"

Background/Objectives: Chronic kidney disease (CKD) is a progressive pathological condition which results in the severe fibrosis of the kidneys. However, the mechanisms of CKD progression and fibrogenesis remain unclear. We wanted to examine the effects that apocynin and hyperbaric oxygen therapy (HBOT) have on renal function and structure in animals with CKD induced through 5/6 nephrectomy (5/6 Nx-L). Methods: Male Wistar rats were divided in 5 groups (n = 8/group) as follows: control—sham-operated rats; Nx-L—rats with 5/6 Nx-L; APO—5/6 Nx-L + apocynin treatment; HBOT—5/6 Nx-L + hyperbaric oxygen treatment, and APO+HBOT—5/6 Nx-L, treated with both treatments. All treatments started 4 weeks after the final step of CKD induction and lasted for 4 weeks. At the end of the experiment, urine samples were collected for the proteinuria assessment and the mean arterial pressure (MAP) was measured. Kidneys were collected for histopathological, Western blot, and immunohistochemical analyses. Results: All treatments significantly decreased MAP compared to the Nx-L group (p < 0.001). In the APO and APO+HBOT groups, the level of proteinuria was decreased compared to the Nx-L group (p < 0.05 and p < 0.01, respectively). All examined treatments significantly decreased the intensity of lesions in the kidney compared to those observed in the Nx-L group (p < 0.001). Isolated treatments with apocynin and HBOT induced a significant decrease in desmin expression compared to the Nx-L group (p < 0.05); meanwhile, they did not affect the levels of fibronectin (FN) and hypoxia-inducible factor-1α (HIF-1α). Combined treatment did not affect desmin expression levels; however, it induced a significant increase in fibronectin expression compared to Nx-L (p < 0.001). Conclusions: Apocynin treatment decreased BP and protein loss, and it improved renal morphology at least partly through the downregulation of desmin expression without changing FN and HIF-1α. Hyperbaric oxygen therapy improved hypertension but failed to significantly affect the level of proteinuria. Combined treatment (apocynin and HBOT) normalized blood pressure (BP) values, renal function, and improved kidney structure by modulating FN and HIF-1α, without affecting desmin protein expression. Further studies are needed to elucidate the mechanisms of slowing down the progression of CKD in this experimental model. © 2024 by the authors.

Background/Objectives: Chronic kidney disease (CKD) is a progressive pathological condition which results in the severe fibrosis of the kidneys. However, the mechanisms of CKD progression and fibrogenesis remain unclear. We wanted to examine the effects that apocynin and hyperbaric oxygen therapy (HBOT) have on renal function and structure in animals with CKD induced through 5/6 nephrectomy (5/6 Nx-L). Methods: Male Wistar rats were divided in 5 groups (n = 8/group) as follows: control—sham-operated rats; Nx-L—rats with 5/6 Nx-L; APO—5/6 Nx-L + apocynin treatment; HBOT—5/6 Nx-L + hyperbaric oxygen treatment, and APO+HBOT—5/6 Nx-L, treated with both treatments. All treatments started 4 weeks after the final step of CKD induction and lasted for 4 weeks. At the end of the experiment, urine samples were collected for the proteinuria assessment and the mean arterial pressure (MAP) was measured. Kidneys were collected for histopathological, Western blot, and immunohistochemical analyses. Results: All treatments significantly decreased MAP compared to the Nx-L group (p < 0.001). In the APO and APO+HBOT groups, the level of proteinuria was decreased compared to the Nx-L group (p < 0.05 and p < 0.01, respectively). All examined treatments significantly decreased the intensity of lesions in the kidney compared to those observed in the Nx-L group (p < 0.001). Isolated treatments with apocynin and HBOT induced a significant decrease in desmin expression compared to the Nx-L group (p < 0.05); meanwhile, they did not affect the levels of fibronectin (FN) and hypoxia-inducible factor-1α (HIF-1α). Combined treatment did not affect desmin expression levels; however, it induced a significant increase in fibronectin expression compared to Nx-L (p < 0.001). Conclusions: Apocynin treatment decreased BP and protein loss, and it improved renal morphology at least partly through the downregulation of desmin expression without changing FN and HIF-1α. Hyperbaric oxygen therapy improved hypertension but failed to significantly affect the level of proteinuria. Combined treatment (apocynin and HBOT) normalized blood pressure (BP) values, renal function, and improved kidney structure by modulating FN and HIF-1α, without affecting desmin protein expression. Further studies are needed to elucidate the mechanisms of slowing down the progression of CKD in this experimental model. © 2024 by the authors.

Neuromuscular excitability is a vital body function, and Mg2+ is an essential regulatory cation for the function of excitable membranes. Loss of Mg2+ homeostasis disturbs fluxes of other cations across cell membranes, leading to pathophysiological electrogenesis, which can eventually cause vital threat to the patient. Chronic subclinical Mg2+ deficiency is an increasingly prevalent condition in the general population. It is associated with an elevated risk of cardiovascular, respiratory and neurological conditions and an increased mortality. Magnesium favours bronchodilation (by antagonizing Ca2+ channels on airway smooth muscle and inhibiting the release of endogenous bronchoconstrictors). Magnesium exerts antihypertensive effects by reducing peripheral vascular resistance (increasing endothelial NO and PgI2 release and inhibiting Ca2+ influx into vascular smooth muscle). Magnesium deficiency disturbs heart impulse generation and propagation by prolonging cell depolarization (due to Na+/K+ pump and Kir channel dysfunction) and dysregulating cardiac gap junctions, causing arrhythmias, while prolonged diastolic Ca2+ release (through leaky RyRs) disturbs cardiac excitation-contraction coupling, compromising diastolic relaxation and systolic contraction. In the brain, Mg2+ regulates the function of ion channels and neurotransmitters (blocks voltage-gated Ca2+ channel-mediated transmitter release, antagonizes NMDARs, activates GABAARs, suppresses nAChR ion current and modulates gap junction channels) and blocks ACh release at neuromuscular junctions. Magnesium exerts multiple therapeutic neuroactive effects (antiepileptic, antimigraine, analgesic, neuroprotective, antidepressant, anxiolytic, etc.). This review focuses on the effects of Mg2+ on excitable tissues in health and disease. As a natural membrane stabilizer, Mg2+ opposes the development of many conditions of hyperexcitability. Its beneficial recompensation and supplementation help treat hyperexcitability and should therefore be considered wherever needed. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.

Neuromuscular excitability is a vital body function, and Mg2+ is an essential regulatory cation for the function of excitable membranes. Loss of Mg2+ homeostasis disturbs fluxes of other cations across cell membranes, leading to pathophysiological electrogenesis, which can eventually cause vital threat to the patient. Chronic subclinical Mg2+ deficiency is an increasingly prevalent condition in the general population. It is associated with an elevated risk of cardiovascular, respiratory and neurological conditions and an increased mortality. Magnesium favours bronchodilation (by antagonizing Ca2+ channels on airway smooth muscle and inhibiting the release of endogenous bronchoconstrictors). Magnesium exerts antihypertensive effects by reducing peripheral vascular resistance (increasing endothelial NO and PgI2 release and inhibiting Ca2+ influx into vascular smooth muscle). Magnesium deficiency disturbs heart impulse generation and propagation by prolonging cell depolarization (due to Na+/K+ pump and Kir channel dysfunction) and dysregulating cardiac gap junctions, causing arrhythmias, while prolonged diastolic Ca2+ release (through leaky RyRs) disturbs cardiac excitation-contraction coupling, compromising diastolic relaxation and systolic contraction. In the brain, Mg2+ regulates the function of ion channels and neurotransmitters (blocks voltage-gated Ca2+ channel-mediated transmitter release, antagonizes NMDARs, activates GABAARs, suppresses nAChR ion current and modulates gap junction channels) and blocks ACh release at neuromuscular junctions. Magnesium exerts multiple therapeutic neuroactive effects (antiepileptic, antimigraine, analgesic, neuroprotective, antidepressant, anxiolytic, etc.). This review focuses on the effects of Mg2+ on excitable tissues in health and disease. As a natural membrane stabilizer, Mg2+ opposes the development of many conditions of hyperexcitability. Its beneficial recompensation and supplementation help treat hyperexcitability and should therefore be considered wherever needed. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.