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Iranian Journal of Basic Medical... Feb 2023Studying the effect of melatonin pretreatment and ischemic preconditioning on renal ischemia-reperfusion injury (IRI).
OBJECTIVES
Studying the effect of melatonin pretreatment and ischemic preconditioning on renal ischemia-reperfusion injury (IRI).
MATERIALS AND METHODS
Forty-eight Wistar rats were randomized into six groups: control, sham operation, IRI (IRI in left kidney + right nephrectomy), IRI+ischemic preconditioning, IRI+Melatonin, and IRI+ischemic preconditioning+Melatonin groups. Melatonin (10 mg/kg) was intraperitoneally injected for 4 weeks before renal IRI. Ischemic preconditioning was performed by three cycles of 2 min-ischemia followed by 5 min-reperfusion period. A right nephrectomy was initially done and the left renal artery was clamped for 45 min. After 24 hr of ischemia-reperfusion, rats were decapitated. Kidney tissue samples were taken for histopathological assessment and the determination of kidney proinflammatory and anti-inflammatory cytokines, apoptotic protein caspase-3, oxidative stress markers, and activities of antioxidant enzymes. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for evaluation of renal function.
RESULTS
Renal IRI animals showed increased levels of creatinine, BUN, tumor necrosis factor-α (TNF-α), caspase-3, total nitrite/nitrate, and malondialdehyde (MDA), and decreased levels of interleukin-13 (IL-13), and activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD). Melatonin pretreatment or ischemic preconditioning resulted in decreased creatinine, BUN, TNF-α, caspase-3, nitrite/nitrate, and MDA, and increased IL-13, GPx, and SOD, with improved histopathological changes. Combined melatonin and ischemic preconditioning showed more effective improvement in renal IRI changes rather than melatonin or ischemic preconditioning alone.
CONCLUSION
Combined melatonin and ischemic preconditioning have better beneficial effects on renal IRI than applying each one alone.
PubMed: 36742133
DOI: 10.22038/IJBMS.2022.67127.14722 -
Neuroreport Mar 2023This study was aimed at evaluating the effects of dexpramipexole (DPX) - a mitochondrial protectant that sustains mitochondrial function and energy production - on...
OBJECTIVES
This study was aimed at evaluating the effects of dexpramipexole (DPX) - a mitochondrial protectant that sustains mitochondrial function and energy production - on cognitive function in a mouse model of sepsis-associated encephalopathy (SAE) induced by peripheral administration of lipopolysaccharide (LPS) and examining the potential mechanisms.
METHODS
C57BL/6 male mice were randomized into one of four treatment protocols: Con+Sal, Con+DPX, LPS+Sal or LPS+DPX. The mice were intraperitoneally (i.p.) injected with LPS or equivalent volumes of normal saline once daily for 3 consecutive days. To evaluate the protective effects of DPX, we administered DPX or normal saline i.p. to the mice once daily for 6 consecutive days. Six mice in each group were decapitated on day 7, and each brain was rapidly removed and separated into two halves for biochemical and histochemical analysis. The remaining surviving mice in each group were subjected to behavioral tests from days 7 to 10.
RESULTS
Peripheral administration of LPS to mice led to learning and memory deficits in behavioral tests, which were associated with mitochondrial impairment and ATP depletion in the hippocampus. Repeated DPX treatment protected the mitochondria against LPS-induced morphological and functional impairment; inhibited the activation of the Nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome-caspase-1-dependent pyroptosis pathway and cytochrome c (Cyt-c)-caspase-3-dependent apoptosis pathway; and attenuated LPS-induced neuroinflammation and cell death in the hippocampus in SAE mice.
CONCLUSIONS
Mitochondria-mediated pyroptosis and apoptosis are involved in the pathogenesis of cognitive deficits in a mouse model of SAE and DPX protects mitochondria and suppresses the mitochondria-medicated pyroptosis and apoptosis pathways, and ameliorates LPS-induced neuroinflammation and cognitive deficits. This study provides theoretical evidence supporting DPX for the treatment of SAE.
Topics: Male; Mice; Animals; Sepsis-Associated Encephalopathy; Pyroptosis; Pramipexole; Lipopolysaccharides; Neuroinflammatory Diseases; Saline Solution; Mice, Inbred C57BL; Apoptosis; Cognition; Mitochondria
PubMed: 36719835
DOI: 10.1097/WNR.0000000000001882 -
Plant Physiology May 2023The inhibition of shoot branching by the growing shoot tip of plants, termed apical dominance, was originally thought to be mediated by auxin. Recently, the importance...
The inhibition of shoot branching by the growing shoot tip of plants, termed apical dominance, was originally thought to be mediated by auxin. Recently, the importance of the shoot tip sink strength during apical dominance has re-emerged with recent studies highlighting roles for sugars in promoting branching. This raises many unanswered questions on the relative roles of auxin and sugars in apical dominance. Here we show that auxin depletion after decapitation is not always the initial trigger of rapid cytokinin (CK) increases in buds that are instead correlated with enhanced sugars. Auxin may also act through strigolactones (SLs) which have been shown to suppress branching after decapitation, but here we show that SLs do not have a significant effect on initial bud outgrowth after decapitation. We report here that when sucrose or CK is abundant, SLs are less inhibitory during the bud release stage compared to during later stages and that SL treatment rapidly inhibits CK accumulation in pea (Pisum sativum) axillary buds of intact plants. After initial bud release, we find an important role of gibberellin (GA) in promoting sustained bud growth downstream of auxin. We are, therefore, able to suggest a model of apical dominance that integrates auxin, sucrose, SLs, CKs, and GAs and describes differences in signalling across stages of bud release to sustained growth.
Topics: Plant Growth Regulators; Indoleacetic Acids; Decapitation; Cytokinins; Sucrose; Sugars; Pisum sativum; Plant Shoots; Gene Expression Regulation, Plant
PubMed: 36690819
DOI: 10.1093/plphys/kiad034 -
Journal of Microscopy and Ultrastructure 2022Cisplatin (Cis) is a highly effective chemotherapeutic agent. However, it produces severe testicular toxicity. It was reported that some antioxidants could overcome this...
The Effect of Selenium Nanoparticles versus Royal Jelly against Cisplatin-Induced Testicular Toxicity in Adult Male Albino Rats: A Light and Transmission Electron Microscopic Study.
BACKGROUND AND AIM
Cisplatin (Cis) is a highly effective chemotherapeutic agent. However, it produces severe testicular toxicity. It was reported that some antioxidants could overcome this toxicity. Selenium nanoparticles and royal jelly (RJ) were among these reported antioxidants. Therefore, this study was designed to compare these two antioxidants in protecting the testes against Cis-induced toxicity.
MATERIALS AND METHODS
This study was conducted on sixty healthy adult male albino rats (weight: 200-220 g) randomized into six groups, ten animals each. Group I (control), Group II (animals received intragastric Nano Selenium), Group III (animals received intragastric RJ), Group IV (animals received an IP injection of Cis 7 mg/kg), Group V (animals received intragastric Nano Selenium, and Cis injection), and Group VI (animals received intragastric RJ and Cis injection). After 10 days, the animals were sacrificed by cervical decapitation. The testes were weighted, and specimens from the left testis were processed for histological and immunohistochemical techniques, whereas specimens from the right testes were prepared for transmission electron microscopic examination.
RESULTS
Cis-treated animals had significantly reduced weight of their testes. Light microscopic examination revealed severe histopathological changes in the germinal epithelium and Leydig cells, confirmed with electron microscopic examination. There was a significant increase in the color area percentage of Caspase-3 immunostaining of the germinal epithelium and Leydig cells, compared to that of the control group. Group II and III were similar to control group. Both Groups V and VI revealed significant preservation compared to the Cis group.
CONCLUSION
Selenium nanoparticles and RJ partially improved testis from Cis-induced toxicity, However, there was no significant difference between both groups.
PubMed: 36687330
DOI: 10.4103/jmau.jmau_44_21 -
Dental Research Journal 2022The aim of this research was to assess the effectiveness of eggshell-membrane (ESM)-containing hyaluronic acid (HA) in the treatment of open gingival embrasure (OGE)...
BACKGROUND
The aim of this research was to assess the effectiveness of eggshell-membrane (ESM)-containing hyaluronic acid (HA) in the treatment of open gingival embrasure (OGE) following orthodontic tooth movement (OTM).
MATERIALS AND METHODS
This study is an quasi experimental research. A total of 24 were equally divided into two groups, treatment (10% HA injection) and control (phosphate-buffered saline [PBS]). A separator was inserted between mandibular incisors to induce an OGE. A volume of 20 μl of either PBS ( = 12) or ESM extract ( = 12) was locally injected within the interdental papilla. Decapitation of animals was made on day 1, 4, and 7 postinjection. The staining was done using hemotoxylin and eosin to observe angiogenesis and Mallory to observe the collagen density. Fourier-transform infrared spectroscopy (FTIR) and thin-layer chromatography (TLC) analysis were performed to detect the amount of HA available in ESM. The results were then compared with independent -tests and the Mann-Whitney test. The level of statistical significance was set at 0.05.
RESULTS
The FTIR and TLC analysis showed that HA was successfully identified in the ESM samples. Local injection of 10% HA induced an increase of angiogenesis compared to the control group on day 1 and 4 postinjection ( < 0.05). Significant differences ( < 0.05) were also noted in the collagen density and the growth of interdental papilla on day 4 and 7 postinjection.
CONCLUSION
ESM has the potential effect of regenerating the interdental papilla construction after OTM by increasing the collagen fiber density and inducing angiogenesis.
PubMed: 36605137
DOI: No ID Found -
Iranian Journal of Basic Medical... Jan 2023We investigated the harmful effects of high fructose corn syrup (HFCS) on learning and memory in the hippocampus and the ameliorative effects of melatonin (Mel).
OBJECTIVES
We investigated the harmful effects of high fructose corn syrup (HFCS) on learning and memory in the hippocampus and the ameliorative effects of melatonin (Mel).
MATERIALS AND METHODS
Thirty-six adult male Sprague Dawley rats were divided into three groups: Group I, control; Group II, HFCS; and Group III, HFCS+Mel. HFCS form F55 was prepared as a 20% fructose syrup solution. Rats in HFCS and HFCS+Mel groups were given drinking water for 10 weeks. Rats in the HFCS+Mel group have been given 10 mg/kg/day melatonin orally for the 6 weeks, in addition to HFCS 55. The Morris water maze (MWM) test was applied to all animals for 5 days to determine their learning and memory levels. After decapitation, one-half of the hippocampus samples were collected for western blot analysis, and another half of the tissues were collected for histopathological and immunohistochemical analyses.
RESULTS
In the HFCS group, there was a significant difference between the time to find the platform in the MWM test and time spent in the quadrant between days 1 and 5 (P=0.037 and P=0.001, respectively). In addition, a decreased level of MT1A receptor, TNF-α, iNOS, osteopontin (OPN), and interleukin-6 (IL-6) expressions were significantly increased in the HFCS group. Melatonin treatment reversed MT1A receptor levels and TNF-α, iNOS, OPN, and IL-6 expressions. During the histopathological examination, increased neuronal degenerations were observed in the HFCS group. Melatonin ameliorated these changes.
CONCLUSION
Consumption of HFCS caused deterioration of learning and memory in adult rats. We suggest that melatonin is effective against learning and memory disorders.
PubMed: 36594054
DOI: 10.22038/IJBMS.2022.65701.14453 -
Journal of Nutrition and Metabolism 2022Hyperglycemia is a major risk factor for endothelial dysfunction. Endothelial dysfunction is associated with the inability of endothelial cells to maintain homeostasis...
BACKGROUND
Hyperglycemia is a major risk factor for endothelial dysfunction. Endothelial dysfunction is associated with the inability of endothelial cells to maintain homeostasis of the cardiovascular system. Regular exercise may be considered as an effective and low-cost nonpharmacological tool for improving vascular function, though there is no agreement on the best type of exercise.
OBJECTIVES
To determine how high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) may prevent endothelial dysfunction under hyperglycemic conditions, and to compare these two interventions.
METHOD
Twenty-four eight-week-old male Wistar rats were randomly assigned into four groups: healthy nonexercising control (C), hyperglycemic control (HG-C), hyperglycemic + HIIT (HG-IT), and hyperglycemic + MICT (HG-CT). Hyperglycemia was induced by a single injection of streptozotocin. Hyperglycemic animals were subjected to HIIT or MICT protocols six days a week for six weeks. Decapitation was performed the day after the exercise protocols were completed. The ascending aorta (until the abdominal artery) was examined. An enzyme-linked immunosorbent assay (ELISA) was used to measure the glucagon-likepeptide-1 (GLP-1), endothelial nitric oxide synthase (eNOS), and tumor necrosis factor-alpha (TNF) levels. A colorimetric assay was used to measure superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels. Quantitative real-time polymerase chain reaction (PCR) was used to measure the expression of the receptor for advanced glycation end-products (RAGE) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B). Hematoxylin and eosin (H&E) staining was used to histologically analyze the aortas.
RESULTS
There was a significantly higher level of GLP-1 and lower expression of RAGE, NF-B, and TNF in the HG-IT and HG-CT group compared to the HG-C group. Microscopic examination of aortic tissue showed a better tissue arrangement in both treatment groups than in the HG-C group. Except for the MDA level, there were no significant differences in any of the measured parameters between the HG-IT and HG-CT groups.
CONCLUSION
Under hyperglycemic conditions, both HIIT and MICT have a protective role against endothelial dysfunction.
PubMed: 36510592
DOI: 10.1155/2022/5631488 -
Heliyon Nov 2022PX receptors modulate synaptic transmission and communication among neurons in the CNS. An increased level of neuronal PX is associated with altered memory in the...
PX receptors modulate synaptic transmission and communication among neurons in the CNS. An increased level of neuronal PX is associated with altered memory in the hippocampal region. Additionally, some evidence suggests that PX receptors downregulate the GABA receptors. In the microglia of drug users, methamphetamine (METH) modifies the expression of certain genes. Therefore, the alterations of PX and GABA gene expression on memory following treatment with/without buprenorphine (BUP) in METH rats were evaluated. Seventy-seven rats were allocated into eleven groups at random (n = 7). Control, METH (10 mg/kg), BUP (6 and 10 mg/kg) for 5 days, BUP (6 and 10 mg/kg) for 14 days, METH (10 mg/kg) + BUP (6 and 10 mg/kg) for 5 days, METH + BUP (6 and 10 mg/kg) for 14 days and withdrawal group. They received their treatments intraperitoneally. After memory assessment, the animals were decapitated, and the gene expression of PX and GABA receptors in the hippocampus was assayed using RT-PCR. The memory and PX and GABA receptor gene expression in METH rats were reduced compared to the control group. The administration of all the different BUP doses increased gene expression in (BUP 6 or 10 mg/kg. 5 days and BUP.10 mg/kg.14 days) + METH groups compared to METH rats. These results demonstrated that METH toxicity severely decreased the level of PX gene expression. Meanwhile, treatment of BUP led to increasing levels of the mentioned gene. Therefore, the potential role of PX and GABA receptor genes in modulating METH addiction is addressed.
PubMed: 36444255
DOI: 10.1016/j.heliyon.2022.e11432 -
Turkish Journal of Medical Sciences Oct 2022Kisspeptin is a neuropeptide with a primary role on the onset of puberty and has beneficial effects on ischemia/ reperfusion (I/R) injury. In this study, we aimed to...
BACKGROUND
Kisspeptin is a neuropeptide with a primary role on the onset of puberty and has beneficial effects on ischemia/ reperfusion (I/R) injury. In this study, we aimed to investigate the effect of kisspeptin administration on striatal I/R injury in mice.
METHODS
Forty adult C57/BL6 mice were randomly divided into four groups: Sham, Kisspeptin, I/R, and I/R + Kisspeptin groups. The groups were administered with either physiological saline (Sham and I/R groups) or kisspeptin (Kisspeptin and I/R + Kisspeptin groups) intraperitoneally 40 min before the operation. A microdialysis probe was placed in the right striatum according to stereotaxic coordinates. During the experimental period, artificial cerebrospinal fluid was passed through the micropump. Then, transient cerebral ischemia was established by compressing both common carotid arteries with an aneurysm clip for 15 min and animals were reperfused for 2 h. Throughout the process of microdialysis (before, during and after I/R period), samples were collected to measure dopamine (DA), noradrenaline (NA), and 3,4-dihydroxyphenylglycine (DHPG) at intervals of 20 min continuously. At the end of the reperfusion period, the animals were decapitated, striatum was dissected, half of the animals were used for oxidative stress analyses (reduced glutathione, glutathione S-transferase (GST), superoxide dismutase (SOD), malondialdehyde (MDA), and the other half were used for histopathology analyses.
RESULTS
Number of glial cells was significantly increased in kisspeptin-administered groups. DA levels in ischemic animals were decreased by kisspeptin administration (p < 0.0001). NA levels were reduced in animals administered with kisspeptin without I/R injury (p < 0.05). DHPG levels reduced during the reperfusion period in ischemic animals (p < 0.05). Kisspeptin did not exhibit a significant antioxidant activity in the ischemic animals, while GST and SOD levels were reduced in the I/R + kisspeptin group compared to the kisspeptin group (p < 0.05).
DISCUSSION
Our results suggest that kisspeptin may be regulating the neurotransmitter release and metabolism, as well as inflammatory response in brain upon I/R injury.
Topics: Animals; Mice; Kisspeptins; Reperfusion Injury; Dopamine; Norepinephrine; Glutathione Transferase; Superoxide Dismutase; Ischemia
PubMed: 36422497
DOI: 10.55730/1300-0144.5493 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Jul 2022To investigate the effects of vagus nerve stimulation(VNS) on hippocampal neuro-inflammatory and α7 nicotinic acetylcholine receptor (α7nAChR) expression in rats with...
To investigate the effects of vagus nerve stimulation(VNS) on hippocampal neuro-inflammatory and α7 nicotinic acetylcholine receptor (α7nAChR) expression in rats with intractable epilepsy (IE). Eighty adult male SD rats (SPF) were randomly divided into control group, model group, VNS group and MLA+VNS group. There were respectively 20 rats in the control group and MLA+VNS group, and because of model failure and animal death, 15 rats and 14 rats in the model group and VNS group were left respectively . Except the control group, the IE model was established in other groups. Only the vagus nerve was isolated in the control group without electrical stimulation; the model group did not take any intervention measures; the VNS group was treated for 4 weeks with VNS after the model was successful; the MLA(3.4 μg/μl, 5 μl) was given to the lateral ventricle in the MLA+VNS group, and then VNS for 4 weeks. Seizure frequency and duration in each group were observed and recorded. And then the rats were decapitated, the hippocampus were quickly separated and 10% tissue homogenate was prepared. The homogenate was centrifuged and the supernatant was extracted. The activities of AChE and ChAT in the supernatant were measured by spectrophotometry, and the levels of TNF-ɑ, IL-6 and IL-1β were detected by ELISA. The expression of α7nAChR in rat hippocampals was detected by Western blot. The expression of α7nAChR on microglias in rat hippocampals was assesed by double-labeled immunofluorescence. ①After VNS for 4 weeks, the frequency and duration of seizures in rats were decreased significantly, which were lower than those of the model group (P<0.01); After treated with MLA +VNS, the frequency and duration of seizures in rats were also reduced significantly, which were lower than those of the model group, but higher than those of the VNS group (P<0.01).②Compared with the control group, the expression of ChAT in the hippocampus of rats in the model group was decreased significantly and the expression of AChE was increased significantly (P<0.01); Compared with the model group, the expressions of ChAT in the hippocampus of rats in the VNS group and MLA+VNS group were increased significantly and the expressions of AChE were decreased significantly (P<0.01); Compared with the VNS group, in the hippocampus of rats in the MLA+VNS group, the expressions of ChAT and AChE had no significant changes (P>0.05). ③Compared with the control group, the expressions of TNF-ɑ, IL-6 and IL-1β in the hippocampus of rats in the model group were increased significantly (P<0.01). Compared with the model group, the expressions of TNF-ɑ, IL-6 and IL-1β in the hippocampus of rats in the VNS group were decreased significantly (P<0.01). Compared with the VNS group, the expressions of TNF-ɑ, IL-6 and IL-1β in the hippocampus of rats in the MLA+VNS group were increased significantly(P<0.01). ④Compared with the control group, the expression of α7nAChR in hippocampus and microglia of rats in the model group was decreased significantly(P<0.01); Compared with the model group, the expression of α7nAChR in hippocampus and microglia of rats in the VNS group was up-regulated significantly (P<0.01); Compared with the VNS group, coexpression of α7nAChR on microglia wasreduced significantly in the MLA+VNS group (P<0.01). VNS has obvious therapeutic effect on IE rats, and its mechanism may be related to activating hippocampal microglia cholinergic anti-inflammatory pathway directly and inhibiting hippocampal neuro-inflammatory response.
Topics: Rats; Male; Animals; Vagus Nerve Stimulation; alpha7 Nicotinic Acetylcholine Receptor; Drug Resistant Epilepsy; Tumor Necrosis Factor-alpha; Interleukin-6; Rats, Sprague-Dawley; Hippocampus; Seizures
PubMed: 36414564
DOI: 10.12047/j.cjap.6274.2022.070