Int J Physiol Pathophysiol Pharmacol [JOURNAL]
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200 papers
Evaluate neuroprotective effect of silibinin using chronic unpredictable stress (cus) model.
Garikapati DR, Shaik PB, Penchalaiah H
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 30697365
UNLABELLED: Chronic unpredictable stressors can produce a situation similar to clinical depression, and such animal models can be used for the preclinical evaluation of antidepressants. Many findings have shown that the...
UNLABELLED: Chronic unpredictable stressors can produce a situation similar to clinical depression, and such animal models can be used for the preclinical evaluation of antidepressants. Many findings have shown that the levels of proinflammatory cytokines (e.g., TNF-α) and oxidative stress (increased lipid peroxidation, decreased glutathione levels, and endogenous antioxidant enzyme activities) are increased in patients with depression. Silibinin is the major active constituent of silymarin, a standardized extract of the milk thistle seeds, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silicristin, silidianin and exhibit antioxidant activity. Objectives The present study was designed to investigate the effect of silibinin on unpredictable chronic stressinduce behavioral and biochemical alterations in mice. METHODS: Mice were subjected to different stress paradigms daily for a period of 45 days to induce depressive like behavior such as memory acquisition, and retention. RESULTS: Chronic treatment with silibinin significantly reversed the unpredictable chronic stress-induced behavioral (improve memory function), biochemical changes (decreased glutathione levels, superoxide dismutas), and inflammation surge (serum TNF-α IL 1β) in stressed mice. CONCLUSION: The study revealed that silibinin exerted effects in behavioral despair paradigm in chronically stressed mice, specifically by modulating central oxidative stress and inflammation.
Profiling of Argonaute-2-loaded microRNAs in a mouse model of frontotemporal dementia with parkinsonism-17.
Kenny A, Hernández F, Avila J … +5 more , Lucas JJ, Henshall DC, Prehn JH, Jiménez-Mateos EM, Engel T
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 30697364
Tauopathies are a group of neurodegenerative diseases characterized by the pathological aggregation of the microtubule-associated protein tau. These include more than 20 diseases, with Alzheimer's disease being the most...
Tauopathies are a group of neurodegenerative diseases characterized by the pathological aggregation of the microtubule-associated protein tau. These include more than 20 diseases, with Alzheimer's disease being the most frequent. While pathological and neurotoxic effects of tau are well documented, the mechanisms by which tau can promote neurodegeneration are less clear. Increasing evidence suggests a functional role for microRNAs in the pathogenesis of tauopathies, with altered expression and function of microRNAs in experimental models and patient brain. To determine whether a pathological expression of tau leads to altered microRNA expression, we investigated a mouse model (VLW), which overexpresses tau carrying three mutations identified in patients suffering from frontotemporal dementia with parkinsonism-17. Argonaute-2-bound microRNAs were co-immunoprecipitated using hippocampal tissue to identify active microRNAs within the model and quantified using a genome-wide high-throughput qPCR-based microRNA platform. While similar numbers of microRNAs are present between wild-type and VLW mice, a prominent increase in Argonaute-2-bound levels of microRNAs could be observed in VLW mice. This included microRNA-134, microRNA-99a and microRNA-101. Subsequent experiments revealed this increase in Argonaute-2 loading of microRNAs to correlate with increased microRNA expression. Our study suggests that a pathological tau overexpression may lead to an increase in active microRNAs, possibly contributing to dysregulation of gene expression and tau-induced pathology.
Does β-caryophyllene protect against renal dysfunction following ischemia-reperfusion injury in the rat?
Hammad FT, Ojha S, Azimullah S … +1 more , Lubbad L
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 30697363
INTRODUCTION: Renal ischemia-reperfusion injury (IRI) causes renal functional alterations which may lead to permanent renal impairment. β-caryophyllene (BCP), a natural bicyclic sesquiterpene, is an important constituent...
INTRODUCTION: Renal ischemia-reperfusion injury (IRI) causes renal functional alterations which may lead to permanent renal impairment. β-caryophyllene (BCP), a natural bicyclic sesquiterpene, is an important constituent of many edible plants including spices. It is an FDA-approved food additive which possesses potent anti-inflammatory and antioxidant activities and has been shown to protect against chemotherapeutics-induced organ toxicities and against ischemic injuries to heart, liver and brain. Oxidative stress and inflammation is a main accompaniment of renal dysfunction, however, the effect of BCP on IRI-induced renal dysfunction has not been investigated yet and therefore the aim of this study was to investigate the effect of BCP on IRI-induced renal dysfunction. METHODS: Wistar rats underwent left renal warm ischemia for 40 minutes. G-BCP (n=13) received oral BCP (50 mg/kg/day) dissolved in a vehicle starting 7 days prior to IRI and continued 7 days thereafter when the renal functions of both kidneys and the markers of oxidative stress and pro-inflammatory cytokines were measured. G-Vx (n=13) underwent similar protocol but received vehicle only. RESULTS: IRI affected hemodynamic (renal blood flow and glomerular filtration rate) and tubular (urine volume, total and fractional urinary sodium excretion) parameters in the left ischemic kidney in G-Vx. Though, BCP did not affect any of these alterations in the ischemic kidney (P>0.05 for all). However, it attenuated the alterations in malondialdehyde (MDA) and glutathione (GSH) in the left ischemic kidney in G-BCP compared to G-Vx (9.3±2.1 vs. 4.8±1.0, P=0.047 and 18.1±2.5 vs. 13.6±1.7, P=0.09, respectively). CONCLUSION: Our study results demonstrate that BCP attenuated the alterations in some of the oxidative stress markers. However, these were not translated in to the protective effects on the haemodynamic and tubular glomerular functions when measured seven days post-IRI. This suggests that BCP has a weak reno-protective effect under ischemic conditions.
The effect of lunasin from Indonesian soybean extract on histopatologic examination and cox-2 expression in dextran sodium sulfate-induced mice colon.
Kusmardi K, Nessa N, Estuningtyas A … +1 more , Tedjo A
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 30697362
Inflammatory bowel disease (IBD) is a condition describing chronic gastrointestinal inflammation. Chronic inflammation in colon can develop into colon cancer. Lunasin has been known to inhibit inflammatory reactions indu...
Inflammatory bowel disease (IBD) is a condition describing chronic gastrointestinal inflammation. Chronic inflammation in colon can develop into colon cancer. Lunasin has been known to inhibit inflammatory reactions induced by lipopolysaccharide . The effect of lunasin to inhibit inflammation is not widely known. In this study, we analyzed the effect of lunasin from soybean to decrease the risk of inflammation by analyzing histopathologic feature and the expression of COX-2. 30 mice are divided into 6 groups. Normal group was not induced by dextran sodium sulfate (DSS). The other groups were induced by 2% DSS through drinking water for 9 days. After 9 days, negative control group did not receive any treatment. The other groups received treatment given lunasin dose 20 mg/kg body weight (BW) and 40 mg/kg BW, commercial lunasin and positive control given aspirin. Treatment was performed for 5 weeks. Inflammatory colon histopathologic examination and immunohistochemical score of COX-2 proteins were analyzed using statistical tests. Lunasin dose 20 mg/kg BW and 40 mg/kg BW were able to significantly reduce inflammation (P<0.05) performed by histopathologic feature with an average score of 2.52 and 2.16 COX-2 expression decreased significantly (P<0.05) with an average score of 43.674 and 33.349. Lunasin dose 20 mg/kg BW and 40 mg/kg BW were able to inhibit inflammation and decrease the expression of COX-2 in colon induced by DSS.
Role of adenylyl cyclase activator in controlling experimental diabetic nephropathy in rats.
Singh L, Rana S, Mehan S
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 30515257
The present study aimed to investigate the role of adenylyl cyclase activator in preventing diabetic nephropathy in rats. Renal function parameters, renal hypertrophy, lipid profile, markers of oxidative stress and free...
The present study aimed to investigate the role of adenylyl cyclase activator in preventing diabetic nephropathy in rats. Renal function parameters, renal hypertrophy, lipid profile, markers of oxidative stress and free radical scavenging activities were assessed. Histopathology was performed to confirm Streptozotocin induced renal morphological changes in diabetic rats. Male Wistar rats were used in the present study to reduce the effect of estrogen. Rats were subjected to high fat diet (HFD) for two weeks followed by low dose of Streptozotocin (STZ) [35 mg/kg, i.p.] to develop experimental diabetic nephropathy in eight weeks. Two weeks treatment with low dose of Forskolin (10 mg/kg) reduced the level of diabetic nephropathy markers but results observed were not significant. Whereas, Forskolin intermediate dose (20 mg/kg) and high dose (30 mg/kg) treated rats significantly attenuated diabetes induced elevated renal function parameters and endogenous antioxidants enzymatic activities. High dose of Forskolin was found to be more effective in attenuating the renal structural and functional abnormalities. Forskolin prevented renal structural and functional abnormalities in diabetic rats. Histopathological evaluation revealed that Forskolin (20 mg/kg and 30 mg/kg) treated diabetic rats demonstrated reduced vacuolar degeneration of tubules and glomerulosclerosis. In the present study, Glibenclamide (0.6 mg/kg) and Atorvastatin (0.5 mg/kg) were used as standard drugs. Our results demonstrated synergistic effects, when high dose of Forskolin was co-administered with standard drugs. In conclusion, treatment with adenylyl cyclase activator, Forskolin in diabetic rats reduced the elevated serum glucose level, biomarkers of renal morphological dysfunction, renal hypertrophy, dyslipidaemia, oxidative stress and improved renal structure, function and enhanced level of endogenous antioxidants. Forskolin has a potential to prevent nephropathy without showing any effect on body weight in diabetic rats.
The evaluation of malignant mucosal melanoma of nasal cavity with a rare occasion.
Kepekci AH, Kig C, Gundogan GI
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 30245777
Malignant mucosal melanoma is an uncommon disease with a low rate of survival. Malignancies of nasal mucosa which usually presents with nasal obstruction, epistaxis and back drip are difficult to treat and often have poo...
Malignant mucosal melanoma is an uncommon disease with a low rate of survival. Malignancies of nasal mucosa which usually presents with nasal obstruction, epistaxis and back drip are difficult to treat and often have poor prognosis. The present case had presented to our clinic with classic symptoms and diagnostic findings of nasal polyposis. Consistently, the patient had previously been diagnosed with and treated for nasal polyposis in another ENT clinic. Physical examination, rhinoscopic examination, computed tomography (CT) scan of the head did not reveal any findings which might imply malignant formations. The operation had been planned for nasal polypectomy and taking deep biopsy specimens. The incised mass showed characteristic features of malignant tissues and the pathology report of the biopsy samples revealed that the specimen showed the histological signs of malignancy. Based on physical examination, CT findings and pathology reports the case was diagnosed as nasal mucosal melanoma. Following an oncosurgical operation, postoperative radio-therapy and chemotherapy were given to the patient and PET/CT examination of the patient did not indicate distant metastases.
The peptide glycyl-ʟ-histidyl-ʟ-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals.
Sakuma S, Ishimura M, Yuba Y … +2 more , Itoh Y, Fujimoto Y
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 30042814
Despite evidence that tripeptide glycyl-ʟ-histidyl-ʟ-lysine (GHK) is an endogenous antioxidant, its mechanism and importance are not fully understood. In the present study, the ability of GHK to reduce levels of reactive...
Despite evidence that tripeptide glycyl-ʟ-histidyl-ʟ-lysine (GHK) is an endogenous antioxidant, its mechanism and importance are not fully understood. In the present study, the ability of GHK to reduce levels of reactive oxygen species (ROS) in Caco-2 cells was evaluated by flow cytometry with the oxidation-sensitive fluorescent dye 2',7'-dichlorodihydrofluorescein diacetate. Further, types of ROS diminished by GHK were assessed by utilizing an electron spin resonance (ESR) spin-trapping technique. GHK reduced the -butyl hydroperoxide-induced increase in ROS levels in Caco-2 cells at concentrations of 10 µM or less. Experiments utilizing an ESR spin-trapping technique revealed that, among hydroxyl (·OH), superoxide (O·), and peroxyl (ROO·) radicals generated by respective chemical reaction systems, GHK diminished signals of both ·OH and ROO·, but not O·. Additionally, the GHK effect on the signal of ·OH was much stronger than those of other well-known antioxidative, endogenous peptides, carnosine and reduced glutathione. These results suggest that GHK can function as an endogenous antioxidant in living organisms, possibly by diminishing ·OH and ROO·.
The role of PPAR-γ and NFKB genes expression in muscle to improve hyperglycemia in STZ-induced diabetic rat following magnesium sulfate administration.
Khosravi F, Kharazmi F, Kamran M … +3 more , Malekzadeh K, Talebi A, Soltani N
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 30042813
The present study was designed to investigate the possible role of magnesium (Mg) on activation of the peroxisome proliferator-activated receptor gamma () and inhibition of nuclear factor-KB (NFKB p65) in muscle to incre...
The present study was designed to investigate the possible role of magnesium (Mg) on activation of the peroxisome proliferator-activated receptor gamma () and inhibition of nuclear factor-KB (NFKB p65) in muscle to increase glucose transporter 4 () gene expression. Fifty rats were divided into five groups, namely non-diabetic control (NDC), Mg-treated non-diabetic control (Mg-NDC), chronic diabetic (CD), Mg-treated chronic diabetic (Mg-CD), and insulin-treated chronic diabetic (Ins-CD). Diabetes was induced with streptozotocin (STZ) injection. The Mg-CD and Mg-NDC groups received 10 g/l of magnesium sulfate (MgSO) added to drinking water and Ins-CD group received 2.5 U/kg of insulin. The blood glucose level and body weight were measured every week. After 16 weeks, intraperitoneal glucose tolerance test (IPGTT) was done and then animals were decapitated, blood samples were taken to determine the plasma levels of Mg and gastrocnemius muscle legs were isolated for both PPAR-γ and (p65) genes and proteins expression. Administration of MgSO improved IPGTT, lowered blood glucose levels and increased gene and protein expression. Diabetes increased gene and protein expression. Although Mg therapy could not decrease gene expression, the protein decreased by Mg therapy. Insulin decreased gene and protein expression, without any effect on gene and protein expression. According to our findings it seems that suppressing protein synthesis and increases in gene and protein expression could help Mg administration to decreases blood glucose levels. But decreasing in gene and protein expression help insulin to decrease blood glucose level.
Potential implication of SGK1-dependent activity change in BV-2 microglial cells.
Asai H, Inoue K, Sakuma E … +2 more , Shinohara Y, Ueki T
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 29755644
It has recently been established that microglial activation is involved in the pathophysiology of various neurological and psychiatric disorders such as amyotrophic lateral sclerosis and schizophrenia. The pathological m...
It has recently been established that microglial activation is involved in the pathophysiology of various neurological and psychiatric disorders such as amyotrophic lateral sclerosis and schizophrenia. The pathological molecular machineries underlying microglial activation and its accelerating molecules have been precisely described in the diseased central nervous system (CNS). However, to date, the details of physiological mechanism, which represses microglial activation, are still to be elucidated. Our latest report demonstrated that serum- and glucocorticoid-inducible kinases (SGK1 and SGK3) were expressed in multiple microglial cell lines, and their inhibitor enhanced the toxic effect of lipopolysaccharide on microglial production of inflammatory substances such as TNFα and iNOS. In the present report, we prepared SGK1-lacked microglial cell line (BV-2) and demonstrated that deficiency of SGK1 in microglia induced its toxic conversion, in which it took amoeboid morphology characteristic of reactive microglia, increased CD68 expression, quickened its proliferation, and showed higher susceptibility to ATP and subsequent cell death. Our data indicate that SGK1 plays pivotal roles in inhibiting its pathological activation, and suggest its potential function as a therapeutic target for the treatment of various disorders related to the inflammation in the CNS.
Tumor associated macrophages deliver iron to tumor cells via Lcn2.
Duan X, He K, Li J … +4 more , Cheng M, Song H, Liu J, Liu P
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 29755643
Cancer cells exhibit an increasing iron demand associated with the tumor progression. But the mechanism of iron accumulation in the tumor microenvironment is still unclear. Tumor associated macrophages (TAMs) in the tumo...
Cancer cells exhibit an increasing iron demand associated with the tumor progression. But the mechanism of iron accumulation in the tumor microenvironment is still unclear. Tumor associated macrophages (TAMs) in the tumor microenvironment may act as extra iron source. However, evidence is still lacking in TAMs as iron donors. In the present study, we found that iron concentration was significantly increased at tumor metastatic stage, which could be attributed to up-regulated expression of lipocalin2 (Lcn2). TAMs in the microenvironment secreted Lcn2. Moreover, TAMs increased intracellular iron concentration in tumor cells via Lcn2 as transporter, which could be restored by Lcn2 antibody neutralization. In conclusion, TAMs increased intracellular iron concentration of the tumor cells via Lcn2 which acted as an iron transporter. Targeting Lcn2 secretion in TAMs to "starve cancer cells" could act as alternative option for tumor therapy.
An improved method for increasing the efficiency of gene transfection and transduction.
Shi B, Xue M, Wang Y … +4 more , Wang Y, Li D, Zhao X, Li X
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 29755642
Transfection and transduction using lentivirus has gained attention in biomedical research. To date, how to reach the maximum transfection and viral transduction efficiency is still challenging. Here we compared the tran...
Transfection and transduction using lentivirus has gained attention in biomedical research. To date, how to reach the maximum transfection and viral transduction efficiency is still challenging. Here we compared the transfection and viral transduction efficiency using commercially available transfection reagents including FuGENE 6, Lipofectamine 2000 and Lipofectamine 3000 in different cell lines and primary cultured cells. Enhanced green fluorescent protein (EGFP) was clearly seen in Eppendorf tubes from harvested cells using Lipofectamine 3000 without using a microscope and UV activation. Strong expression of EGFP was observed in HEK293 cells, mouse primary cortical neurons and human umbilical vein endothelial cells (HUVECs) using confocal microscopy. Western blot showed the strongest EGFP expression using cell lysates from Lipofectamine 3000 transfected HEK293 cells and transduced HUVECs compared with Lipofectamine 2000 or FuGENE 6 reagents. Using Cx43 shRNA lentivirus combined with Lipofectamine 3000 transfection reagent, we can achieve about 90% Cx43 knockdown efficacy in HUVECs. Therefore, our results suggest that a much higher transfection and viral transduction efficiency can be attained by using Lipofectamine 3000 transfection reagent.
Ischemic preconditioning attenuates acute lung injury after partial liver transplantation.
Liu Q, Rehman H, Krishnasamy Y … +2 more , Lemasters JJ, Zhong Z
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 29755641
Pulmonary complications frequently occur after liver transplantation and are often life-threatening. Thus, we investigated whether hepatic ischemic preconditioning (IP) attenuates acute lung injury (ALI) after small-for-...
Pulmonary complications frequently occur after liver transplantation and are often life-threatening. Thus, we investigated whether hepatic ischemic preconditioning (IP) attenuates acute lung injury (ALI) after small-for-size liver transplantation. Rat livers were explanted after 9-min ischemia plus 5-min reperfusion, reduced to 50% of original size , and implanted into recipients with approximately twice the donor body weight, resulting in quarter-size liver grafts (QSG). After QSG transplantation, hepatic Toll-like receptor 4 (TLR4) and tumor necrosis factor-α (TNFα ) expression increased markedly and high mobility group box-1 (HMGB1), an endogenous damage-associated molecular pattern molecule (DAMP), was released from QSG into the blood. IP blunted TLR4 and TNFα expression and HMGB1 release from QSG. In the lungs of QSG recipients without IP treatment, nuclear factor-κB (NF-κB) activation and intercellular adhesion molecule (ICAM)-1 expression increased; alveolar septal walls thickened with increased cellularity as neutrophils, monocytes/macrophage and T lymphocytes infiltrated into alveolar septa and alveolar spaces; and pulmonary cleaved caspase-8 and -3 and TUNEL-positive cells increased. In contrast, in the lungs of recipients of ischemic-preconditioned QSG, NF-κB activation and ICAM-1 expression were blunted; leukocyte infiltration was decreased; and alveolar septal wall thickening, caspase activation, and cell apoptosis were attenuated. IP did not increase heat-shock proteins in the lungs of QSG recipients. In conclusion, toxic cytokine and HMGB1 released from failing small-for-size grafts leads to pulmonary adhesion molecule expression, leukocyte infiltration and injury. IP prevents DAMP release and toxic cytokine formation in small-for-size grafts, thereby attenuating ALI.
Melatonin and tumeric ameliorate aging-induced changes: implication of immunoglobulins, cytokines, DJ-1/NRF2 and apoptosis regulation.
Ismail IA, El-Bakry HA, Soliman SS
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 29755640
Aging is associated with several biological, physiological, cellular and histological changes. In the present study, we investigated the effect of aging on different signaling pathways, including antioxidant system, apop...
Aging is associated with several biological, physiological, cellular and histological changes. In the present study, we investigated the effect of aging on different signaling pathways, including antioxidant system, apoptosis and immune status. Several natural products were used to ameliorate and block aging-related changes. Melatonin and turmeric have been known to ameliorate and decrease aging-related changes. However, the exact mechanism(s) of their action is not fully understood. In the present study, we tried to uncover the regulatory mechanism(s) by which melatonin and turmeric work against aging. We found that aging differentially regulated blood serum immunoglobulins; increased IgA and decreased IgE. Furthermore, all the serum cytokines investigated (TNF-α, IFN-γ, IL-6 and IL-8) were highly increased by aging. In addition, the antioxidant upstream regulators; DJ-1 and NRF2 were markedly repressed with aging in thymus tissues. We also found that aging induced apoptosis promoting genes p53 and Bax mRNA in thymus tissues. Finally, we found clear histological changes in thymus and spleen tissues. Administration of either melatonin or tumeric clearly ameliorated and blocked to some extinct the effect of aging. Altogether, aging was associated with downregulation of antioxidant regulators; DJ-1 and NRF2, promoted apoptosis and induced changes in the immune status. Furthermore, melatonin and tumeric markedly reversed the action of aging through activating DJ-1/NRF2 signaling pathway and inhibiting p53/Bax apoptotic pathway.
Acupuncture for alcohol use disorder.
Chen P, Li J, Han X … +4 more , Grech D, Xiong M, Bekker A, Ye JH
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 29593851
Alcohol use disorder (AUD) is a common medical and social problem, affecting about 240 million people in the world. To address this major health concern, the currently available treatments for AUD need to be improved. Ac...
Alcohol use disorder (AUD) is a common medical and social problem, affecting about 240 million people in the world. To address this major health concern, the currently available treatments for AUD need to be improved. Acupuncture, a popular form of complementary and alternative therapy, is emerging as an effective treatment for AUD. This review summarizes how preclinical and clinical studies are related to the application of acupuncture for AUD. These studies suggest that if used correctly, acupuncture may effectively reduce alcohol intake, attenuate alcohol withdrawal syndrome, and rebalance AUD-induced maladaptation in neurotransmitters and hormones in related brain areas. The progress of research in this field is at an early stage. Future investigations with rigorous design and carefully constructed protocols are still needed.
Systemic delivery of selective EP1 and EP3 receptor antagonists attenuates pentylenetetrazole-induced seizures in mice.
Reschke CR, Poersch AB, Masson CJ … +6 more , Jesse AC, Marafiga JR, Lenz QF, Oliveira MS, Henshall DC, Mello CF
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 29593850
Neuroinflammation plays a major role in brain excitability and may contribute to the development of epilepsy. Prostaglandin E (PGE) is a direct mediator of inflammatory responses and, through EP receptors, plays an impor...
Neuroinflammation plays a major role in brain excitability and may contribute to the development of epilepsy. Prostaglandin E (PGE) is a direct mediator of inflammatory responses and, through EP receptors, plays an important role in neuronal excitability. Pharmacological evidence supports that centrally-administered EP1 and EP3 receptor antagonists reduced acutely evoked seizures in rats. Translation of these findings would benefit from evidence of efficacy with a more clinically relevant route of delivery and validation in another species. In the current study we investigated whether the systemic administration of EP1 and EP3 agonists and antagonists modulate pentylenetetrazole (PTZ)-induced seizures in mice. In addition, it was examined whether these compounds alter Na, K-ATPase activity, an enzyme responsible for the homeostatic ionic equilibrium and, consequently, for the resting membrane potential in neurons. While the systemic administration of EP1 and EP3 antagonists (ONO-8713 and ONO-AE3-240, respectively) attenuated, the respective agonists (ONO-DI-004 and ONO-AE-248) potentiated PTZ-induced seizures (all compounds injected at the dose of 10 µg/kg, s.c., 30 min before PTZ challenge). Co-administration of either EP1 or EP3 agonist with the respective antagonists nullified the anticonvulsant effects of EP1/3 receptor blockade. In addition, EP1 and EP3 agonists exacerbated PTZ-induced decrease of Na, K-ATPase activity in both cerebral cortex and hippocampus, whereas, EP1 and EP3 antagonists prevented PTZ-induced decrease of Na, K-ATPase activity in both structures. Our findings support and extend evidence that EP1 and EP3 receptors may be novel targets for the development of anticonvulsant drugs.
Ascorbic acid and sodium benzoate synergistically aggravates testicular dysfunction in adult Wistar rats.
Kehinde OS, Christianah OI, Oyetunji OA
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 29593849
BACKGROUND: The effect of the concomitant use of sodium benzoate (NaB) and ascorbic acid on human health remains controversial. Therefore, the current study is designed to investigate the effect of NaB and ascorbic acid...
BACKGROUND: The effect of the concomitant use of sodium benzoate (NaB) and ascorbic acid on human health remains controversial. Therefore, the current study is designed to investigate the effect of NaB and ascorbic acid on the testicular function of adult Wistar rats. METHODS: Adult Wistar rats were randomly allotted into Control (vehicle; received 1 ml of distilled water), NaB-treated (SB-treated; received 100 mg/kg body weight; ), ascorbic acid-treated (AA-treated; received 150 mg/kg ) and NaB+ ascorbic acid-treated (SB+AA-treated) groups. The treatment lasted for 28 days and the administration was given orally. The body weight change was monitored. Semen analysis, biochemical assay and histological examination were performed. RESULTS: Treatment with NaB significantly altered the cytoarchitecture of testicular tissue, sperm quality, testicular endocrine function and oxidative stress status without any alteration in body weight gain compared to control. In addition, treatment with NaB+ ascorbic acid exacerbated testicular tissue disruption, impaired sperm quality and testicular endocrine impairment with significant reduction in oxidative stress and unaltered body weight gain when compared with NaB-treated group. CONCLUSION: This study suggests that ascorbic acid and NaB synergistically aggravates testicular dysfunction. This is independent of oxidative stress status.
Saturated fatty acids bound to albumin enhance osteopontin expression and cleavage in renal proximal tubular cells.
Cobbs A, Ballou K, Chen X … +2 more , George J, Zhao X
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 29593848
Osteopontin (OPN) is one of the proinflammatory cytokines upregulated in the kidneys of diabetic animals and patients with nephropathy. An increase in urinary albumin and albumin-bound fatty acids (FA) presents a proinfl...
Osteopontin (OPN) is one of the proinflammatory cytokines upregulated in the kidneys of diabetic animals and patients with nephropathy. An increase in urinary albumin and albumin-bound fatty acids (FA) presents a proinflammatory environment to the proximal tubules in proteinuric kidney diseases including diabetic nephropathy. This study was designed to examine if FA overload could stimulate OPN expression and cleavage in renal tubule epithelial cells. OPN gene and protein expression was examined in the kidney of Zucker diabetic (ZD) rats and cultured proximal tubular cells exposed to either bovine serum albumin (BSA) or BSA conjugated with palmitic acid (PA), the most abundant saturated plasma FA. Real-time PCR analysis confirmed an upregulation of renal cortical OPN gene correlated with albuminuria and nephropathy progression in ZD rats at the age of 7-20 weeks. Immunofluorescence staining of kidney sections revealed a massive induction of OPN protein in albumin-overloaded proximal tubules of ZD rats. A significant increase in both intact and cleaved OPN proteins was further demonstrated in the diabetic kidney and urine samples, which was attenuated by antiproteinuric treatment with losartan, an angiotensin II receptor blocker. When exposed to fatty acid-free BSA, NRK-52E cells exhibited an increase in protein levels of full-length and cleaved OPN. Moreover, the increase in OPN fragments was greatly enhanced in the presence of PA (250-500 µM). Together, our results support a stimulatory effect of albumin and conjugated FA on OPN expression and cleavage in renal tubule epithelial cells. Thus, besides lowering albuminuria/proteinuria, mitigating circulating FAs may be an effective intervention for preventing and slowing down the progression of nephropathy associated with obesity and type 2 diabetes.
The crosstalk between autonomic nervous system and blood vessels.
Sheng Y, Zhu L
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 29593847
The autonomic nervous system (ANS), comprised of two primary branches, sympathetic and parasympathetic nervous system, plays an essential role in the regulation of vascular wall contractility and tension. The sympathetic...
The autonomic nervous system (ANS), comprised of two primary branches, sympathetic and parasympathetic nervous system, plays an essential role in the regulation of vascular wall contractility and tension. The sympathetic and parasympathetic nerves work together to balance the functions of autonomic effector organs. The neurotransmitters released from the varicosities in the ANS can regulate the vascular tone. Norepinephrine (NE), adenosine triphosphate (ATP) and Neuropeptide Y (NPY) function as vasoconstrictors, whereas acetylcholine (Ach) and calcitonin gene-related peptide (CGRP) can mediate vasodilation. On the other hand, vascular factors, such as endothelium-derived relaxing factor nitric oxide (NO), and constriction factor endothelin, play an important role in the autonomic nervous system in physiologic conditions. Endothelial dysfunction and inflammation are associated with the sympathetic nerve activity in the pathological conditions, such as hypertension, heart failure, and diabetes mellitus. The dysfunction of the autonomic nervous system could be a risk factor for vascular diseases and the overactive sympathetic nerve is detrimental to the blood vessel. In this review, we summarize findings concerning the crosstalk between ANS and blood vessels in both physiological and pathological conditions and hope to provide insight into the development of therapeutic interventions of vascular diseases.
New insights into Nod-like receptors (NLRs) in liver diseases.
Xu T, Du Y, Fang XB … +4 more , Chen H, Zhou DD, Wang Y, Zhang L
Int J Physiol Pathophysiol Pharmacol · 2018 · PMID 29593846
Activation of inflammatory signaling pathways is of central importance in the pathogenesis of alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH). Nod-like receptors (NLRs) are intracellular innate immu...
Activation of inflammatory signaling pathways is of central importance in the pathogenesis of alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH). Nod-like receptors (NLRs) are intracellular innate immune sensors of microbes and danger signals that control multiple aspects of inflammatory responses. Recent studies demonstrated that NLRs are expressed and activated in innate immune cells as well as in parenchymal cells in the liver. For example, NLRP3 signaling is involved in liver ischemia-reperfusion (I/R) injury and silencing of NLRP3 can protect the liver from I/R injury. In this article, we review the evidence that highlights the critical importance of NLRs in the prevalent liver diseases. The significance of NLR-induced intracellular signaling pathways and cytokine production is also evaluated.
Methanolic extract of elicits dose-dependent diuretic, natriuretic and kaliuretic activities without causing electrolyte impairment, hepatotoxicity and nephrotoxicity in rats.
Adeosun OI, Olaniyi KS, Amusa OA … +2 more , Jimoh GZ, Oniyide AA
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29348800
(Kolanut) is conventionally used in tropical Africa for the treatment of all kinds of ailments such as migraine, morning sickness, metabolic disorders etc. However, this study was designed to investigate the diuretic, na...
(Kolanut) is conventionally used in tropical Africa for the treatment of all kinds of ailments such as migraine, morning sickness, metabolic disorders etc. However, this study was designed to investigate the diuretic, natriuretic and kaliuretic activities of methanolic extract of (MECN) in male Wistar rats. Adult male Wistar rats were randomly allotted into control (25 ml/kg .), furosemide (20 mg/kg ; standard), MECN (100 mg/kg), MECN (200 mg/kg), MECN (300 mg/kg), MECN (400 mg/kg), MECN (500 mg/kg), MECN (600 mg/kg) groups with n=6. The extract was prepared as previously described and the treatment lasted for 14 days. Urine volume and diuretic indices were estimated. Urine electrolytes, plasma electrolytes, plasma/renal AST/ALT, plasma creatinine and urea were assayed using flame photometry and standard colorimetric method respectively.Administration of different doses of significantly altered body weight gain and water intake but not food intake compared with control group. There were significant increases in urine volume and urine electrolytes (Na, K and Cl), a decrease in plasma/renal ALT and AST activities, a decrease in plasma creatinine and urea concentration and no alteration in plasma electrolytes when compared with control and furosemide-treated groups. Our study suggests that MECN elicits diuretic, natriuretic, and kaliuretic activities without causing electrolyte impairment, hepatotoxicity and nephrotoxicity. These effects are dose-dependent.
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