Role of Farnesoid Receptors and Nrf2-mediated Genes in Gentamicin-induced Nephrotoxicity in Rat: A Time-course Study.

INTRODUCTION: Farnesoid-X-activated receptor (FXR) is considered as an upstream controller which could influence the other key regulatory genes encoding cellular antioxidant defense system. METHODS: Thirty-five male Wistar rats (240 ± 20 g) were randomly allocated into five groups: 1) control, 2) received gentamicin (100 mg/kg/d) for three days (GM-3d), 3) seven days (GM-7d), 4) 10 days (GM-10d), and 5) 14 consecutive days (GM-14d). Biochemical measurements of BUN and serum creatinine (SCr), histological assessment of renal samples as well as molecular analysis using real-time qRT-PCR were used to investigate the pattern of changes in different levels. RESULTS: Administration of gentamicin was associated with a significant increase in the BUN and SCr until the 10th day, which then suddenly dropped at the day 14. Meantime, the maximum histological distortion was also seen on the 10th day but in a similar pattern, 14th day was associated with clear improvement. Compared to the control value, the maximum reduction in the mRNA expression of Farnesoid X-activated receptor (FXR), nuclear factor erythroid 2-related factor 2 (Nrf2) and Glutathione cysteine ligase-modulatory subunit (GCLM), occurred at the 3rd and 7th days, respectively. Compared to the control, the mRNA expression of the mentioned genes significantly increased up to day 14. Apart from the 3rd day, the mRNA expression of alpha-glutathione S-transferase (α-GST) and superoxide dismutase (SOD) showed a similar descending and ascending pattern at 7th and 10th days, respectively. CONCLUSION: The expression of FXR, as an upstream controller gene and its downstream pathways mediated by Nrf2, could play a role in gentamicin-induced nephrotoxicity but the pattern of expression was rather biphasic at the acute phase or the subacute ones.  DOI: 10.52547/ijkd.7523.

Potential use of angiotensin receptor blockers in skin pathologies.

Renin-angiotensin system (RAS) components such as angiotensin II, angiotensin receptors (AT1R and AT2R), and angiotensin-converting enzyme (ACE) are expressed in different cell types of the skin. Through AT1R, angiotensin II increases proinflammatory cytokines contributing to fibrosis, angiogenesis, proliferation, and migration of immune cells to the skin. In contrast, AT2R suppresses the effects mentioned above. Many studies show that angiotensin receptor blockers (ARBs) and angiotensin-converting enzymes (ACEi) reduce the proinflammatory cytokines and fibrogenic factors including transforming growth factor ß (TGF-ß), Connective tissue growth factor (CTGF), and IL-6. This review article provides a detailed research study on the implications of ARBs in wound healing, hypertrophic scar, and keloids. We further discuss the therapeutic potentials of ARBs in autoimmune and autoinflammatory skin diseases and cancer, given their anti-fibrotic and anti-inflammatory effects.

Effects of platelet-rich plasma on the memory impairment, apoptosis, and hippocampal synaptic plasticity in a rat model of hepatic encephalopathy.

OBJECTIVES: In the present study, we aimed to determine whether intraperitoneal injection of platelet-rich plasma (PRP) could have a neuroprotective effect on learning, memory, and synaptic plasticity impairment as well as hippocampal apoptosis in rats with hepatic encephalopathy induced by bile duct ligated (BDL). METHODS: The rats were divided into four groups: the control, sham, BDL+ V (vehicle), and BDL+ PRP. The BDL rats were treated with PRP immediately after the surgery, and the injection was done every 3 days for 30 days. The passive avoidance and Morris water maze tests were used for the evaluation of learning and memory. The long-term potentiation (LTP), basal-synaptic transmission, and paired-pulse ratio, as an index for measurement of neurotransmitter release probability, were evaluated by field-potential recording. After taking a blood sample for assessment of the liver enzymes, the animals were sacrificed and their hippocampus was removed for evaluation of cleaved caspase-3 by Western blot. RESULTS: Serological assessment of the liver function showed that BDL severely impaired the liver function. Also, PRP treatment could partially improve the liver dysfunction along with recovery in fear memory and spatial learning memory performance, LTP, basal-synaptic transmission, and neurotransmitter release probability. PRP-treated rats also showed a significant reduction in neuronal apoptosis in the CA1 area. CONCLUSIONS: The results of this study suggest that PRP improves cognitive performance and synaptic plasticity in BDL rats via direct neuroprotective property and/or indirectly by improvement of hepatic dysfunction.

Nandrolone decanoate negatively reverses the beneficial effects of exercise on cardiac muscle via sarcolemmal, but not mitochondrial K(ATP) channel.

ATP-sensitive potassium channels are supposed to have a substantial role in improvement of cardiac performance. This study was performed to evaluate whether nandrolone decanoate (ND) and (or) exercise training could affect the expression of cardiac K(ATP) channel subunits. Thirty-five male albino Wistar rats were randomly divided into 5 groups, including sedentary control (SC), sedentary vehicle (SV), sedentary ND (SND), exercise control (EC), and exercise and ND (E+ND). Exercise training was performed on a treadmill 5 times per week. ND was injected (10 mg/kg/week, i.m.) to the rats in the SND and E+ND groups. Following cardiac isolation, the expression of both sarcolemmal and mitochondrial subunits of K(ATP) channel was measured using Western blot method. The expression of sarcolemmal, but not mitochondrial, subunits of K(ATP) channel (Kir6.2 and SUR2) of EC group was significantly higher compared with SC group while ND administration (SND group) did not show any change in their expression. In the E+ND group, ND administration led to decrease of the over-expression of sarcolemmal Kir6.2 and SUR2 which was previously induced by exercise. There was no significant association between the mitochondrial expression of either Kir6.2 or SUR2 proteins and administration of ND or exercise. Supra-physiological dosage of ND negatively reverses the effects of exercise on the cardiac muscle expression of sarcolemmal, but not mitochondrial, K(ATP) channel subunits.