Physiology and Pharmacology
Volume:26 Issue: 2, Jun 2022

Heart rate variability represents the performance of the cardiac autonomic nervous system (ANS) and is defined as the fluctuation of beat-to-beat between two successive R-waves (RR intervals). Accordingly, addressing the actions of the ANS in sickle cell disease helps in identifying the possible risk factors of sudden death. The clinical staging of the disease improves the diagnosis and the quality of the treatments.

This systematic review analyzed the data of the basal autonomic reactions in sickle cell anemia (SCA) and sickle cell trait (SCT) patients compared to healthy people. In this study, 441 articles were retrieved from PubMed, ProQuest, SCOPUS, Embase, and Web of Science databases. Some of them were removed based on the inclusion and exclusion criteria, and finally, seven articles remained for analysis.

The data analysis of the included studies demonstrated that the vagal modulation at the basal condition decreased in SCA or SCT patients compared to the control group.

The sympathovagal balance was altered in SCA or SCT patients, and an increasing trend was observed in sympathetic nerve activities.

Nigella sativa (N. sativa)in the family of Ranunculaceae, has been traditionally used as food additive and spice. N. sativa showed protective effects on respiratory system including trachea responsiveness and lung inflammation in various animals’ models studies. The possible therapeutic effects of N. sativa on asthma were investigated in this systematic review study.

The published studies were searched in the different databases including; PubMed, Web of Science (ISI), Scopus and Cochrane, until September 2020, by: (asthma) AND (“Nigella sativa”) OR (“Nigella sativa oil”) OR (Black seed). All unrelated articles such as duplicates, animal and review studies as well as clinical studies without control group were excluded from obtained studied. Then 9 articles were considered for further evaluation.

After analyzing 9 articles including 434 participants, these following results were achieved: N. sativa improved the asthma control test and pulmonary function tests values, while reduced respiratory symptoms including, cough and wheeze. Furthermore, N. sativa, reduced eosinophils count and serum levels of pro-inflammatory mediators such as interleukin-4 and immunoglobulin E, while increased production of anti-inflammatory mediator such as interferon-γ in the serum.

The results of this systematic review article revealed that supplementation of N. sativa might be effective in the control or treatment of asthma.

Neuroinflammation is a primary pathophysiological condition that is associated with cognitive impairment and neurodegenerative diseases. The present study was designed to evaluate the effects of enriched environment (EE) on passive avoidance (PA) memory impairment caused by lipopolysaccharide (LPS) induced neuroinflammation.

Twenty-eight male Wistar rats were assigned into the following groups: 1, control; 2, control+ EE; 3, LPS and 4, LPS+ EE. LPS injection (1mg/kg/i.p.) was done on days 1, 3, 5 and 7 of experiment. Two different housing conditions were used in this experiment, including a standard environment house and an enriched environment house. The passive avoidance task was used to examine animals learning and memory performance. The hippocampal level of interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) was also measured using sandwich-ELISA method.

Obtained data indicated that LPS significantly impaired passive avoidance memory, decreased the step-through latency and increased the time spent in the dark compartment of the LPS treated group compared to the control group. On the other hand, EE housing could significantly ameliorate memory impairment. Hippocampal IL-6 level was increased and BDNF was decreased in the LPS group, whereas EE could decrease and increase IL-6 and BDNF levels in the LPS+EE group, respectively.

EE should probably be considered as an alternative strategy in neuroinflammatory diseases to minimize the memory impairment.

The hippocampal nitric oxide/cGMP signaling pathway plays a crucial role in memory processing. Phosphodiesterase interacts with this signaling pathway. There are controversial reports regarding the effect of sildenafil, a phosphodiesterase inhibitor, on learning and memory. Therefore, the effects of acute administration (intrahippocampal/ intra-dentate gyrus injection) of sildenafil on long-term potentiation (LTP) of rats were investigated.

The rats were anesthetized with urethane and placed in a stereotaxic device for field potential recording. After ensuring a steady-state baseline response, a single intraperitoneal injection of saline or sildenafil (2 and10 µg/kg) was done. The population spike amplitude, the excitatory postsynaptic potentials (EPSPs) slope and paired-pulse stimuli (as an inhibitory interneuron) were compared between groups.

The results showed that population spike amplitude and EPSP slope significantly increased after sildenafil administration (10µg/kg) following titanic stimulation compared with the saline group. However, the sildenafil (2µg/kg) and control groups showed no difference regarding population spike amplitude and EPSP slope. Sildenafil had no significant effects on recurrent inhibition.

The obtained results indicated that acute administration of sildenafil improved LTP via direct effects on the hippocampus of intact rats. Thus, sildenafil may enhance learning and memory processing by modulating the hippocampal synapse.

Aminoglycoside antibiotics including gentamicin are used for treatment of gram-negative bacteria-induced infections; however, gentamicin has severe side effects such as nephrotoxicity. Date palm pollen (DPP), as a herbal medicine is believed to have some antiinflammatory and antioxidative stress effects. In this study the protective effect of DPP extract were evaluated after its phytochemical analysis on gentamicin-induced nephrotoxicity.

Wistar rats allocated into five groups including control, sham, gentamicin and two groups that received gentamicin along with DPP extract (200 or 400 mg/kg). Plasma urea and creatinine concentrations were measured and oxidative stress was assessed by evaluating MDA, FRAP, CAT and SOD. NF-κB, TNF-α and ICAM-1 gene expression levels along with the leukocyte infiltration were measured for evaluating inflammation. Histopathological damages were also measured by studying H&E-stained tissue sections.

The gentamicin receiving group had increased plasma urea and creatinine, increased MDA, and decreased FRAP, CAT and SOD activities in the kidney. The gentamicin administration also increased the TNF-α, NF-κB and ICAM-1 gene expression, infiltration of leukocytes and tissue damages in the kidney. DPP extract caused a partial or complete recovery of all these damages.

In conclusion, DPP extract protects the kidney against the side effects of gentamicin and improves its function and histopathological damages. The underlying mechanism is likely to decrease the NF-κB gene expression and consequently reducing pro-inflammatory cytokine genes expression, infiltration of leukocytes and oxidative stress. The DPP extract also increased the cellular antioxidant reserves.

The toxicity induced by toxic substances and medications is one of the principal reasons for acute kidney injury. The purpose of this study was to investigate the effect of Cinnamomum zeylanicum and Zingiber officinale extracts on the kidney of the rats intoxicated with carbon tetrachloride (CCl4).

In this study, thirty-six Wistar rats randomly divided into six groups: I) control, II) cinnamon 25mg/kg + ginger 125mg/kg, III) CCl4, IV) CCl4+ cinnamon 50mg/kg, V) CCl4+ ginger 250mg/kg, VI) CCl4+ cinnamon 25mg/kg and ginger 125mg/kg. Cinnamomum zeylanicum and Zingiber officinale extracts were injected for 14 days. On the 14th day, the rats in the CCl4 and the pretreatment groups were administered with 1mg/kg of CCl4 and olive oil mixture (1:1 v/v). Forty-eight hours after the injection of CCl4, blood samples were taken to conduct subsequent biochemical tests. Also, the kidney removed and histological alterations as well as oxidative markers were investigated.

The administration of CCl4 increased the levels of urea, uric acid, creatinine and malondialdehyde; while decreased the levels of serum albumin, total protein, total antioxidant capacity and renal tissue antioxidant enzymes. Pretreatment with Cinnamomum zeylanicum and Zingiber officinale extracts, especially with a combination of them, led to considerable improvement in these values compared to the CCl4 group.

The results suggest that hydroalcoholic extracts of Cinnamomum zeylanicum and Zingiber officinale, alone or simultaneously, have protective effects against free radicals produced during CCl4 metabolism.

Renal ischemia/reperfusion injury (IRI) may influence distance organ such as lung. The severity of IRI induced- lung insult can be affected by gender and reperfusion time alteration. The aim of this study was to determine gender differences in renal IR inducedlung injury in different reperfusion time.

Eighty male and female rats were assigned into 8 groups, 4 groups in each gender including: sham, renal ischemia for 45min by clamping renal vessels followed by 3, 24 or 48h reperfusion. Blood samples were obtained for measuring the serum level of blood urea nitrogen (BUN), creatinine (Cr), nitrite and malondialdehyde (MDA). The kidneys and lung tissues were removed and used for MDA and nitrite measurements and the histological changes evaluation. The lung water content was calculated.

In both genders, the rise in Cr and BUN reached the peak at 24h reperfusion. A significant increment was seen in female serum level of nitrite compared with males after 3h reperfusion. The renal MDA level of male increased during 3h reperfusion but not seen in females. The enhanced lung and renal tissues damages were depended to reperfusion time in both genders. The water content of lung was reduced in 3h of reperfusion groups.

Sex effects and the time of reperfusion may be the important factors to consider clinical therapeutic of renal IRI as well as its impact on remote organs.

“Regulator of G protein signaling” (RGS) proteins are a family of various proteins that are expressed in different tissues and accelerate hydrolysis rate of GTP to GDP by several thousand-fold increase in GTPase activity of Gα subunit. Thus, they act as negative regulators of G protein-coupled receptors (GPCRs) signaling. In this study, the effect of CCG-50014, a RGS4 inhibitor, on isolated aorta and left atrium of normal and diabetic rats has been investigated.

Isolated aorta was treated with increasing concentrations of phenylephrine and acetylcholine. Isolated left atrium was treated with increasing concentrations of acetylcholine and isoprenaline; both in the absence and presence of CCG-50014. The pEC50 (negative logarithm of the concentration which produces half maximal response) and maximum response of each compound were extracted from concentration-response curves.

Pre-treatment of aorta with CCG-50014 had no important effect on the response to phenylephrine and acetylcholine. CCG-50014 decreased isoprenaline inotropic potency on normal atrium but had no effect on its maximum response. In diabetic atrium, CCG-50014 dramatically reduced both the pEC50 and maximum response of isoprenaline. CCG-50014 did not affect normal atrium response to acetylcholine but in diabetic atrium, it caused a small yet significant decrease in the pEC50 of acetylcholine while increased its maximum relaxing effect.

It seems that RGS4 is not involved in the termination of GPCRs signaling in rat aorta. In atrium, RGS4 inhibition unexpectedly results in attenuation of β-adrenoceptormediated atrial contractility, which is much more prominent in diabetes.

Depression impairs brain functions and memory processes. In a state of depression, escitalopram (as an antidepressant drug) and exercise (as an alternative lifestyle) both affect brain functions. Therefore, this study compared the therapeutic effects of exercise, using escitalopram at two different doses and exercise-accompanied escitalopram on different aspects of brain functions in rats with depression.

Male rats were randomly allocated into nine different groups of control, sham, depression, depression-rest, depression-exercise, depression-escitalopram 10, depressionescitalopram 20, depression-escitalopram 10-exercise and depression-escitalopram 20-exercise. Chronic restraint stress (6h/day, 14 days) was applied to induce depression. The escitalopram injections and treadmill running (1h/day, 14 days) were performed after the stress-induced depression. Moreover, different aspects of brain functions like learning, memory, memory consolidation and locomotor activity were evaluated via the passive avoidance test.

The results indicated that depression disrupted learning, memory and memory consolidation. Escitalopram at a dose of 20mg/kg, exercise-accompanied escitalopram 20mg/ kg and only exercise improved them significantly. In rats with depression, escitalopram at a dose of 10mg/kg (with and without exercise) enhanced memory in depression non-significantly. Moreover, the locomotor activity was decreased in groups with exercise-accompanied escitalopram 20mg/kg and exercise compared to only allowing a rest period after depression.

Overall, escitalopram 20mg/kg, exercise-accompanied escitalopram 20mg/kg and only exercise had therapeutic effects on memory improvement in subjects with depression. Since the combination of escitalopram 20mg/kg and exercise had a partial additive effect, it was the best treatment protocol for reversing the memory deficits in rats with depression.

Stem cell therapy is considered as a promising strategy to treat neurological disorders. Amongst different cell types that are recruited under these devastating conditions, epidermal neural crest stem cells (EPI-NCSCs) are known as potential candidates. Acetylsalicylic acid (ASA or aspirin) is one of the commonly prescribed drugs that might affect the therapeutic potential of the transplanted stem cells. Hence, the present study aimed to evaluate the effects of ASA on the expression of fundamental growth factors involved in restorative pathways expressed by EPI-NCSCs in vitro for possible combination therapy’s purpose.

EPI-NCSCs were obtained from the rat’s hair follicle. The appropriate ASA concentration to treat the cells was defined based on the MTT assay and then the obtained cells were treated with 80 or 800µM ASA for 1, 3 or 7 days. The relative expressions of Bdnf, Gdnf, Ngf, Neurotrophin-3, Vegf, Gfap, and doublecortin were finally assessed by qRT-PCR.

The obtained data revealed that the growth factors expressions are influenced by concentration and duration of the treatment applied. One-day ASA treatment was found to be able to increase the expression of all the evaluated genes, except Gdnf and doublecortin, which elevated three days later. Herein, seven-day treatment of stem cells with 800µM ASA resulted in higher levels of Bdnf, Vegf, and doublecortin.

Therefore, combination of aspirin and EPI-NCSCs might increase the therapeutic potential of these stem cells to treat neurological disorders.