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Showing papers on "Intraperitoneal injection published in 2021"


Journal ArticleDOI
TL;DR: In this paper, the beneficial power of a new compound called Hidrox®, containing 40-50% hydroxytyrosol, in counteracting the damage related to fertility induced by cyclophosphamide was evaluated.
Abstract: Background: Every year, men use cyclophosphamide to treat various cancers and autoimmune diseases. On the one hand, this chemotherapy often has the beneficial effect of regressing the tumor, but on the other hand, it leads to infertility due to excessive oxidative stress and apoptosis in the testes caused by its metabolite, acrolein. Methods: The objective of this study was to evaluate the beneficial power of a new compound called Hidrox®, containing 40–50% hydroxytyrosol, in counteracting the damage related to fertility induced by cyclophosphamide. The study was conducted using a single intraperitoneal injection of cyclophosphamide at a dose of 200 mg/kg b.w, in distilled water at 10 mL/kg b.w. The treatment was administered via the oral administration of Hidrox® at a dose of 50 mg/kg. Results: Our study confirms that the use of cyclophosphamide causes a series of sperm and histological alterations strongly connected with oxidative stress, lipid peroxidation, and apoptosis. Conclusion: Our results demonstrate for the first time that Hidrox® protects testes from CYP-induced alterations by the modulation of physiological antioxidant defenses.

28 citations


Journal ArticleDOI
TL;DR: Overall, co-treatment elicited more efficacy than that of the individual regimen, and there was enhanced brain antioxidant status with a lower acetylcholinesterase activity and oxidative-inflammatory stress biomarkers.
Abstract: Selenium nanoparticles (SeNPs) are well reported to exhibit pharmacological activities both in vitro and in vivo. However, literature is devoid of studies on the impact of SeNPs and/or metformin (M) against streptozotocin (STZ)-mediated oxidative brain injury and behavioral impairment. Consequently, to fill this gap, diabetes was induced in male Wistar rats by feeding with 10% fructose solution for 2 weeks, followed by a single dose intraperitoneal injection of STZ (40 mg/kg body weight [bwt]). After rats were confirmed diabetic, they were treated orally with 0.1 mg/kg bwt of SeNPs ± M (50 mg/kg bwt), and normal control (NC) received citrate buffer (2 mg/mL) for 5 weeks. In comparison with the diabetic control (DC), SeNPs, and/or M significantly (p < 0.05) lowered blood glucose levels, but increased insulin secretion and pancreatic β-cell function. An increase in locomotor and motor activities evidenced by improved spontaneous alternation, locomotor frequency, hinding, and increased mobility time were observed in treated groups. In addition, there was enhanced brain antioxidant status with a lower acetylcholinesterase (AChE) activity and oxidative-inflammatory stress biomarkers. A significant downregulation of caspase 3 and upregulation of parvalbumin and Nrf2 protein expressions was observed in treated groups. In some of the studied parameters, treated groups were statistically (p < 0.05) insignificant compared with the normal control (NC) group. Overall, co-treatment elicited more efficacy than that of the individual regimen.

26 citations


Journal ArticleDOI
TL;DR: The final fasting blood glucose level of the experimental animals showed no significant difference when compared to that of the control rats, and the effect of vernonia amygdalina on Glutathione reductase and GlUTathione-S-transferase in alloxan induced diabetic wistar rats was found to be unchanged.
Abstract: s This research was conducted to examine the effect of vernonia amygdalina on Glutathione reductase and Glutathione-S-transferase in alloxan induced diabetic wistar rats. Sixty-six (66) adult male wistar rats weighing between 100 and 250 g were used for the study. The animals were induced by intraperitoneal injection of 60 mg of alloxan. The animals were divided into 11 groups of six (6) rats in phase 1 and phase 2 (normal control, crude extract, Metformin, glycoside, saponin and alkaloid) respectively. After 28days treatment, the rats were sacrificed using a gaseous anesthetic agent (chloroform), blood samples were collected from inferior Vena Cava for biochemical analysis and pancreas harvested for histopathological examination. The final fasting blood glucose level of the experimental animals showed no significant difference when compared to that of the control rats (at p

20 citations


Journal ArticleDOI
TL;DR: Zhang et al. as discussed by the authors used Re-Du-Ning injection (RDN) for the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in female C57BL/6J mice.

20 citations


Journal ArticleDOI
TL;DR: The data indicate that it is advisable to deliver lipophilic substances, like tamoxifen, by oral gavage instead of intraperitoneal injection to help to understand some of the undesired effects observed in animal experiments.
Abstract: Oil is frequently used as a solvent to inject lipophilic substances into the peritoneum of laboratory animals. Although mineral oil causes chronic peritoneal inflammation, little is known whether other oils are better suited. We show that olive, peanut, corn, or mineral oil causes xanthogranulomatous inflammation with depletion of resident peritoneal macrophages. However, there were striking differences in the severity of the inflammatory response. Peanut and mineral oil caused severe chronic inflammation with persistent neutrophil and monocyte recruitment, expansion of the vasculature, and fibrosis. Corn and olive oil provoked no or only mild signs of chronic inflammation. Mechanistically, the vegetal oils were taken up by macrophages leading to foam cell formation and induction of cell death. Olive oil triggered caspase-3 cleavage and apoptosis, which facilitate the resolution of inflammation. Peanut oil and, to a lesser degree, corn oil, triggered caspase-1 activation and macrophage pyroptosis, which impair the resolution of inflammation. As such, intraperitoneal oil administration can interfere with the outcome of subsequent experiments. As a proof of principle, intraperitoneal peanut oil injection was compared with its oral delivery in a thioglycolate-induced peritonitis model. The chronic peritoneal inflammation due to peanut oil injection impeded the proper recruitment of macrophages and the resolution of inflammation in this peritonitis model. In summary, the data indicate that it is advisable to deliver lipophilic substances, like tamoxifen, by oral gavage instead of intraperitoneal injection. IMPLICATIONS: This work contributes to the reproducibility of animal research by helping to understand some of the undesired effects observed in animal experiments.

18 citations


Journal ArticleDOI
TL;DR: H2O2 injection could impair antioxidant status and enhance anaerobic metabolism of breast muscle in broilers.

18 citations


Journal ArticleDOI
TL;DR: In this paper, the effects of activated P2X7R-associated oxidative stress after intracerebral hemorrhage were investigated in mice, and the results indicated that activation aggravated NOX2-induced oxidative stress through the activation of the ERK1/2 and NF-κB pathways.

17 citations


Journal ArticleDOI
TL;DR: It is demonstrated that melatonin can improve oocyte quality and maintain hormone homeostasis in mice exposed to glyphosate.

13 citations


Journal ArticleDOI
TL;DR: It is concluded that LPS intraperitoneal injection can activate the innate immune response and modulate the hormonal profile of the bullfrogs, with effects more pronounced 24’h than 6 h after treatment.
Abstract: Host's defense against external challenges activates an inflammatory response regulated by a set of chemical signals, including hormones. These immunomodulatory hormones, such as corticosterone, testosterone, and melatonin, trigger the systemic immune responses responsible for inflammatory assembly and resolution. This study aimed to investigate the effects of an immune challenge on endocrine and innate immune responses in the bullfrog (Lithobates catesbeianus). Adult males were intraperitoneally injected with lipopolysaccharide (LPS; 2 mg/kg) or saline, and blood samples were collected 6 and 24 h after injection for measurement of neutrophil/lymphocyte ratio, blood leukocyte phagocytosis, plasma bacterial killing ability, and plasma levels of corticosterone, melatonin, and testosterone. Our results showed LPS-induced increased neutrophil/lymphocyte ratio and leukocyte phagocytosis, and decreased melatonin and testosterone plasma levels, which were more pronounced 24 h after injection. Overall, we conclude that LPS intraperitoneal injection can activate the innate immune response and modulate the hormonal profile of the bullfrogs, with effects more pronounced 24 h than 6 h after treatment.

13 citations


Journal ArticleDOI
TL;DR: In this paper, the authors used assays of serum protein and tracer extravasation to determine that BBB disruption occurring after status epilepticus in mice was sufficient to permit passage of systemically injected Ant-134 into the brain parenchyma.

13 citations


Journal ArticleDOI
Jinghan Li1, Simeng Wang1, Jiaqi Duan1, Peixin Le1, Chao Li1, Yongpei Ding1, Rui Wang1, Yonggang Gao1 
TL;DR: In this paper, Liu et al. investigated the mechanism of how RES prevents liver injury induced by iron overload in mice and found that RES can effectively eliminate oxygen free radicals and resist lipid peroxide damage.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the effect of melatonin on the brain injury in diabetic rats and found that melatonin significantly reduced caspase-3 and Bax as well as significantly increase Bcl-2 protein and GFAP-positive astrocytes indicating its anti-apoptotic effect.

Journal ArticleDOI
Siyu Chen1, Lei Zhou1, Jingquan Sun1, Yaqian Qu1, Min Chen1 
TL;DR: In this article, the role of the cAMP-PKA pathway in intramuscular triglyceride accumulation and mitochondrial content increase was identified, and the results provided a possibility for metabolism-related mechanisms of lactate-induced mitochondria content increase.
Abstract: The glycolytic product of exercise, lactate, has long been recognized to promote lipid accumulation by activation of G-protein-coupled receptor 81 (GPR81) and inhibition of the cyclic adenosine monophosphate-protein kinase A (cAMP -PKA) pathway in adipose tissue. Whether lactate causes a similar process in skeletal muscle is unclear. Lactate might also improve mitochondria content in skeletal muscle; however, the mechanism is not clarified either. In this study, using intramuscular injection of lactate to the gastrocnemius and intraperitoneal injection of forskolin (activator of cAMP-PKA pathway), we identified the role of the cAMP-PKA pathway in lactate-induced intramuscular triglyceride accumulation and mitochondrial content increase. The intramuscular triglyceride level in the gastrocnemius increased after 5weeks of lactate injection (p<0.05), and this effect was blocked by forskolin injection (p<0.05). Corresponding expression level changes of GPR81, P-PKA/PKA, P-CREB/cAMP-response element binding protein (CREB), and proteins related to lipid metabolism suggest that lactate could induce intramuscular triglyceride accumulation partly through the inhibition of the cAMP-PKA pathway. Meanwhile, the intramuscular expression of citrate synthase (CS) and the activity of CS increased after 5weeks of lactate injection (p<0.05), but the change of CS expression was not blocked by forskolin injection, suggesting other mechanisms might exist. Consequently, exploration for other potential mechanisms that might contribute to the lactate-induced mitochondria content increase was conducted. We found an increase in the contents of lactate-related metabolites in skeletal muscle mitochondria after acute lactate injection (the p-value of each analysis is less than 0.05). LHDA was also validated to exist in mitochondria in this study. These results provide a possibility for metabolism-related mechanisms of lactate-induced mitochondria content increase. Future study is needed to validate this hypothesis. In conclusion, lactate-induced intramuscular triglyceride accumulation is achieved by inhibition of lipolysis, and this process is regulated by the cAMP-PKA pathway. Promoted lipogenesis also contributes to lactate-induced triglyceride accumulation, and this process might also be regulated by the cAMP-PKA pathway. Lactate injection might increase mitochondria content and cAMP-PKA pathway might have a limited contribution, while other metabolism-related mechanisms might play a prominent role.

Journal ArticleDOI
TL;DR: In this paper, the authors established a diabetic mouse model by intraperitoneal injection of STZ and high-fat diet, and evaluated the blood-glucose-lowering activity of the pea component PGP2 at different doses.
Abstract: Polysaccharides have hypoglycemic activity and pea protein has high nutritional value. The purified pea glycoprotein PGP2 has been shown to inhibit the activity of α-glucosidase and α-amylase in previous studies. To study the mechanism of PGP2-induced blood glucose lowering in vivo, this paper established a diabetic mouse model by intraperitoneal injection of STZ and high-fat diet, and evaluated the blood-glucose-lowering activity of the pea component PGP2 at different doses. The results showed that intragastric administration of PGP2 could effectively reduce diabetic weight loss and polyphagia symptoms, reduce fasting blood glucose levels in mice, and improve oral glucose tolerance levels in mice. PGP2 could promote insulin secretion and had a protective effect on mouse organs. After intragastric administration of PGP2 in mice, the serum levels of total cholesterol, triglycerides and low-density lipoprotein decreased. PGP2 up-regulated the gene expression of insulin receptor substrates IRS-1 and IRS-2 in liver tissues, thereby reducing insulin resistance. Based on the above experimental results, PGP2 had good hypoglycemic activity and was expected to be developed as a natural medicine for the treatment of type II diabetes.

Journal ArticleDOI
TL;DR: In this paper, the authors examined the uterine and ovarian effects of PCB126 and test the hypothesis that the aryl hydrocarbon receptor (AHR) is required for PCB126-induced reproductive toxicity.

Journal ArticleDOI
TL;DR: Zhang et al. as discussed by the authors investigated the toxicological effect of mercuric chloride (HgCl2 ) exposure on reproductive system in male mice and found that HgCl 2 exposure disrupts the reproductive system and induces testicular immunosuppression and fibrosis via inhibition of the CD74 signaling pathway.
Abstract: Mercury as a toxic heavy metal will accumulate in the body and induce various diseases through the food chain. However, it is unknown that the detailed mechanism of reproductive disorder induced by inorganic mercury in male mice to date. This study investigated the toxicological effect of mercuric chloride (HgCl2 ) exposure on reproductive system in male mice. Male Kunming mice received normal saline daily or HgCl2 (3 mg/kg bodyweight) by intraperitoneal injection for a week. The reproductive function was evaluated, and the HgCl2 exposure induced the decline of sperm quality, pregnancy rate, mean litter size, and survival rate. Notably, we firstly found the HgCl2 -induced immunosuppression and fibrosis in mice testis according to the results of RNA sequencing. Collectively, these findings demonstrate that HgCl2 exposure disrupts the reproductive system and induces testicular immunosuppression and fibrosis via inhibition of the CD74 signaling pathway in male mice.

Journal ArticleDOI
TL;DR: In this article, an intraperitoneal injection of 100 mg/kg/day dextran-iron for 5 days, the epididymis adipose showed a remarkable increase in iron.
Abstract: Iron overload is tightly connected with metabolic disorders. Excess iron in the adipose and its roles in dyslipidemia are of interest to be identified. In acute iron overload mice receiving intraperitoneal injection of 100 mg/kg/day dextran-iron for 5 days, the epididymis adipose showed a remarkable increase in iron. Serum triglyceride and low-density lipoprotein cholesterol (LDL-C) levels were increased and high-density lipoprotein cholesterol (HDL-C) level was decreased, while serum alkaline phosphatase, aspartate aminotransferase, glucose, and insulin were not affected. The serum-cytokine-microarray showed that adipocytokines, including adiponectin, leptin, and resistin were significantly decreased. Other serum cytokines, including pro-insulin cytokines, inflammatory cytokines, chemokines, and growth factors were not changed, except that ghrelin and chemokine RANTES were increased. Iron overload decreased expressions of adiponectin and leptin both in vivo and in vitro. Intraperitoneal injection of recombinant leptin at 1 μg/g in acute iron overload mice had no significant effects on serum levels of TC, TG, HDL-C, and LDL-C, while intraperitoneal injection of recombinant adiponectin at 3 μg/g partially restored serum TG level through improving activities of lipoprotein lipase and hepatic lipase, but abnormal serum LDL-C and HDL-C were not redressed, suggesting other mechanisms also existed. In conclusion, the adipose responds to iron overload at an early stage to interfere with lipid metabolism by secreting adipocytokines, which may further affect glucose metabolism, inflammation, and other iron overload-induced effects on the body.

Journal ArticleDOI
TL;DR: Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both doxorubicinol and DOXol, which were found in the plasma of HCC Rats pretreated with ADI.
Abstract: Background Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC. Methods Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI. Conclusions Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.

Journal ArticleDOI
TL;DR: Arbutin is a natural glycoside that possesses antioxidant, anti-inflammatory, and neuroprotective properties as discussed by the authors, which suggests that the suppression of A2A receptors-cyclic adenosine monophosphate pathway may be able to restore the disrupted dopamine transmission that results in motor symptoms in Parkinson's disease.

Journal ArticleDOI
TL;DR: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo, which has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.
Abstract: Background Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.

Journal ArticleDOI
TL;DR: Oral administration of the lyophilized aqueous extract of date seeds and insulin injection for 30 days significantly decreased blood glucose levels in STZ-diabetic rats and protected them against undesirable changes in lipid parameters, including cholesterol, triglycerides, LDL cholesterol, VLDL cholesterol and atherosclerosis index.
Abstract: OBJECTIVES Several epidemiological data indicate that chronic hyperglycemia is associated with behavioral changes such as anxiety and depressive symptoms. Date seeds, one of the most potent products with potential antioxidant activities and possess many benefits against hyperglycemia and its complication. The aim of the current study was to explore the potential effect of date seeds extract on biochemical and behavioral changes (anxiety and depression) in streptozotocin (STZ)-diabetic rats. METHODS Rats were divided into four groups as follows: normal control, diabetic control, diabetic treated with the lyophilized aqueous extract of the date seed (2,000 mg/kg) (LAE-DS) and diabetics treated with insulin (4 UI/day). Experimental diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). After 24 days treatment period, anxiety and depressive behaviors were evaluated using four behavioral tests. After sacrifice, blood samples were collected to evaluate lipid parameters. In addition, rat organs (kidney, liver and brain) were dissected out in order to estimate lipid peroxidation levels as oxidative stress marker. RESULTS Oral administration of the lyophilized aqueous extract of date seeds and insulin injection for 30 days significantly decreased blood glucose levels in STZ-diabetic rats and protected them against undesirable changes in lipid parameters, including cholesterol, triglycerides, LDL cholesterol, VLDL cholesterol and atherosclerosis index. Compared to untreated diabetic rat, a significant decrease in lipid peroxidation levels in kidney, liver and brain (Hippocampus and prefrontal cortex) were observed after treatment with insulin or LAE-DS in diabetic rats. Furthermore, insulin and LAE-DS administration prevented anxiety-related behaviors in STZ-diabetic rats. CONCLUSIONS Therefore, it would be possible to combine this extract with insulin and use it as an antioxidant supplement for type 1 diabetic patients.

Journal ArticleDOI
TL;DR: In this article, the authors demonstrate that pre-treatment of L. plantarum K8 lysates reduced LPS-induced TNF-α production in THP-1 cells by down-regulating the early signals of mitogen-activated protein kinase (MAPK) and nuclear factor-κb (NF-κB).
Abstract: We previously showed that Lactiplantibacillus plantarum K8 and its cell wall components have immunoregulatory effects. In this study, we demonstrate that pre-treatment of L. plantarum K8 lysates reduced LPS-induced TNF-α production in THP-1 cells by down-regulating the early signals of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB). The down-regulation of signals may be caused by the induction of negative regulators involved in toll-like receptor (TLR)-mediated signaling. However, co-treatment with high concentrations of L. plantarum K8 lysates and lipopolysaccharide (LPS) activated the late signaling of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-κB pathways and resulted in the induction of absent in melanoma 2 (AIM2) inflammasome-mediated interleukin (IL)-1β secretion. Intraperitoneal injection of L. plantarum K8 lysates in LPS-induced endotoxin shock mice alleviated mortality and reduced serum tumor-necrosis factor (TNF)-α, IL-1β, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. In addition, the mRNA levels of TNF-α, IL-1β, and IL-6 decreased in livers from mice injected with L. plantarum K8 followed by LPS. Hematoxylin and eosin (H&E) staining of the liver showed that the cell size was enlarged by LPS injection and slightly reduced by L. plantarum K8 lysate pre-injection followed by LPS injection. Macrophage infiltration of the liver also decreased in response to the combination injection compared with mice injected with only LPS. Taken together, our results show that although L. plantarum K8 lysates differentially regulated the production of LPS-induced inflammatory cytokines in THP-1 cells, the lysates inhibited overall inflammation in mice. Thus, this study suggests that L. plantarum K8 lysates could be developed as a substance that modulates immune homeostasis by regulating inflammation.

Journal ArticleDOI
TL;DR: The results indicate that injection of TCH has multifaceted neuroprotective effects against MCAO via regulation of the various NOS isoforms.
Abstract: Purpose: Cerebral ischemic stroke, caused by obstruction of the blood flow to the brain, initiates a complex cascade of pathophysiological changes. The aim of the present study was to assess the protective role and the underlying mechanism of troxerutin and cerebroprotein hydrolysate (TCH) injections for five days in rats subjected to middle cerebral artery occlusion (MCAO).Materials and Methods: Male Sprague-Dawley rats treated with either TCH or a vehicle (0.9% saline) via intraperitoneal injection were examined one or three days after MCAO.Results: TCH alleviated neurological deficits and reduced infarct volume, innate immune response, blood-brain barrier destruction, and suppressed cell apoptosis. The therapeutic effects of TCH were achieved by diminished neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS), and increased endothelial nitric oxide synthase (eNOS). Furthermore, L-NAME showed an inhibitory effect against TCH after MCAO on eNOS expression, NO and peroxynitrite production, neurobehavioral score, and infarct volume.Conclusions: The results indicate that injection of TCH has multifaceted neuroprotective effects against MCAO via regulation of the various NOS isoforms.

Journal ArticleDOI
TL;DR: For evaluation of the effect of high-fat diet on the development of diabetic complications, the rats were maintained on standard or highfat diet for 3 weeks and the results showed significant changes in hematological parameters, physical and biochemical parameters of the urine, and in development of thermal allodynia were different after 15-week standard and high fat diets as mentioned in this paper.
Abstract: For evaluation of the effect of high-fat diet on the development of diabetic complications, the rats were maintained on standard or high-fat diet. In 3 weeks, diabetes mellitus was modeled by single intraperitoneal injection of streptozotocin. Changes in hematological parameters, physical and biochemical parameters of the urine, and in the development of thermal allodynia were different after 15-week standard and high-fat diets.

Journal ArticleDOI
TL;DR: In this article, the effect of DY131 on lipopolysaccharide (LPS)-induced liver injury was evaluated and it was shown that pretreatment with DY 131 ameliorated liver injury as demonstrated by reduced liver enzyme release, improved liver morphological damage, and attenuated oxidative stress, inflammation and apoptosis.
Abstract: Sepsis-associated liver dysfunction remains a challenge in clinical practice with high mortality and limited specific therapies. DY131 is a pharmacological agonist of the orphan receptor estrogen-related receptor (ERR) γ which plays a crucial role in regulating energy generation, oxidative metabolism, cell apoptosis, inflammatory responses, etc. However, its role in acute liver injury is unknown. In this study, we evaluated the effect of DY131 on lipopolysaccharide (LPS)-induced liver injury. Mice were pretreated with DY131 through intraperitoneal injection at a dose of 5 mg/kg/day for 3 days prior to LPS challenge (10 mg/kg). 24 h later, they were anesthetized and sacrificed. Blood and liver tissues were collected for further studies. In a separate experiment, mice were treated with saline (vehicle) or DY131 for 3 days to evaluate the toxicity of DY131. We found that ERRγ was downregulated in the liver tissues from LPS-treated mice. Pretreatment with DY131 ameliorated LPS-induced liver injury as demonstrated by reduced liver enzyme release (ALT, AST, and LDH), improved liver morphological damage, and attenuated oxidative stress, inflammation and apoptosis. Meanwhile, DY131 had no significant side effects on hepatic and renal functions in mice. Finally, transcriptomics analysis revealed that the dysregulated pathways associated with inflammation and metabolism were significantly reversed by DY131 in LPS-treated mice, providing more evidence in favor of the protective effect of DY131 against LPS-induced liver injury. Altogether, these findings highlighted the protective effect of DY131 on LPS-induced hepatotoxicity possibly via suppressing oxidative stress, inflammation, and apoptosis.

Journal ArticleDOI
TL;DR: In this paper, the interrelationship between systemic iron, intestinal barrier and the development of intestinal inflammation in a dextran sulfate sodium (DSS) induced experimental colitis mice model was characterized.

Journal ArticleDOI
TL;DR: In this paper, the effect of Nicotinamide mononucleotide (NMN) intraperitoneal injection on UVB-induced photodamage was investigated in mice.
Abstract: Objective Ultraviolet light is an important environmental factor that induces skin oxidation, inflammation, and other diseases. Nicotinamide mononucleotide (NMN) has the effect of anti-oxidation and improving various physiological processes. This study explores the protective effect of NMN monomers given via intraperitoneal injection on UVB-induced photodamage. Methods We used a murine model of UVB-induced photodamage to evaluate the effect of an NMN monomer on photoaging skin by assessing skin and liver tissue sections, serum and skin oxidative stress levels, inflammatory markers, mRNA expression, and protein expression of skin- and liver-related genes. Results The results showed that NMN treatment blocked UVB-induced photodamage in mice, maintaining normal structure and amount of collagen fibers, normal thickness of epidermis and dermis, reducing the production of mast cells, and maintaining complete organized skin structure. NMN intraperitoneal injection also maintained the normal morphology of the mouse liver after UVB exposure. Meanwhile, NMN intraperitoneal injection was found to increase antioxidant ability and regulate the proinflammatory response of the skin and liver to UVB irradiation by enhancing the activity of antioxidant enzymes, release of anti-inflammatory cytokines, reduction of hydrogen peroxide production (H2O2), and decreased inflammatory cytokines. Furthermore, RT-qPCR results indicated that NMN reduced oxidative stress of skin and liver by promoting the activation of the AMP-activated protein kinase (AMPK) signaling pathway and further increasing the expression of downstream antioxidant genes of AMPK. RT-qPCR results also revealed that NMN treatment could downregulate the mRNA expression of interleukin (IL)-6, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α, and upregulate NF-kappa-B inhibitor-α (IκB-α) and interleukin (IL)-10 by inhibiting the activation of nuclear factor-κBp65 (NFκB-p65). Finally, NMN upregulated AMPK, IκB-α, SOD1, and CAT in the skin and downregulated NF-κBp65 protein expression, which is in line with the RT-qPCR results. Conclusion Based on the above results, NMN monomer treatment with intraperitoneal injection also block the photodamage caused by UVB irradiation in mice by regulating the oxidative stress response and inflammatory response.

Journal ArticleDOI
TL;DR: In this article, the effect of remdesivir on renal fibrosis and its downstream mechanisms was investigated in the presence of COVID-19 in patients with kidney impairment, and the results showed that remdesir and its active nucleoside metabolite GS-441524 inhibited the expression of fibrotic markers (fibronectin and aSMA).
Abstract: Aim: Kidney impairment is observed in patients with COVID-19. The effect of anti-COVID-19 agent remdesivir on kidneys is currently unknown. We aimed to determine the effect of remdesivir on renal fibrosis and its downstream mechanisms. Methods: Remdesivir and its active nucleoside metabolite GS-441524 were used to treat TGF-β stimulated renal fibroblasts (NRK-49F) and human renal epithelial (HK2) cells. Vehicle or remdesivir were given by intraperitoneal injection or renal injection through the left ureter in unilateral ureteral obstruction (UUO) mice. Serum and kidneys were harvested. The concentrations of remdesivir and GS-441524 were measured using LC-MS/MS. Renal and liver function were assessed. Renal fibrosis was evaluated by Masson's trichrome staining and Western blotting. Results: Remdesivir and GS-441524 inhibited the expression of fibrotic markers (fibronectin and aSMA) in NRK-49F and HK2 cells. Intraperitoneal injection or renal injection of remdesivir attenuated renal fibrosis in UUO kidneys. Renal and liver function were unchanged in remdesivir treated UUO mice. Two remdesivir metabolites were detected after injection. Phosphorylation of Smad3 that was enhanced in cell and animal models for renal fibrosis was attenuated by remdesivir. In addition, the expression of Smad7, an anti-fibrotic factor, was increased after remdesivir treatment in vitro and in vivo. Moreover, knockdown of Smad7 blocked the antifibrotic effect of GS and RDV on renal cells. Conclusion: Remdesivir inhibits renal fibrosis in obstructed kidneys.

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TL;DR: The findings suggest that FIBCD1 could ameliorate chemotherapy-induced gastrointestinal toxicity by reducing weight loss; however, the mechanism of this possible protective effect remains to be defined warranting additional investigations.
Abstract: Chemotherapy-induced gastrointestinal toxicity is a common adverse event during chemotherapeutic treatment. No uniformly applicable strategies exist to predict, prevent, or treat gastrointestinal toxicity. Thus, a goal of mucositis research is to identify targets for therapeutic interventions and individualized risk prediction. Fibrinogen C domain containing 1 (FIBCD1) is a transmembrane protein expressed in human intestinal epithelial cells with functions in the innate immune system. Previous observations have shown that FIBCD1 ameliorates dextran sulfate sodium (DSS)–induced intestinal inflammation in vivo. We evaluated the effect of FIBCD1 in a murine model of chemotherapy-induced gastrointestinal toxicity and inflammation. Transgenic (Tg) mice overexpressing FIBCD1 in the intestinal epithelium (Fibcd1Tg) and wild-type (WT) littermates (C57BL/6N) were randomized to receive an intraperitoneal injection of doxorubicin 20 mg/kg or saline and were terminated 2 or 7 days after the injection. Gastrointestinal toxicity was evaluated by weight change, intestinal length, villus height/crypt depth, and histological mucositis score. Expression of inflammatory markers (IL-6, IL-1β, and Tnfα) was measured by quantitative real-time PCR in intestinal tissue samples. Following doxorubicin treatment, WT mice exhibited an increased weight loss compared with Tg littermates (p < 0.001). No differences between genotypes were seen in mucositis score, intestinal length, villus height/crypt depth, or IL-6, IL-1β, and Tnfα expression. Our findings suggest that FIBCD1 could ameliorate chemotherapy-induced gastrointestinal toxicity by reducing weight loss; however, the mechanism of this possible protective effect remains to be defined warranting additional investigations.

Journal ArticleDOI
TL;DR: This study showed that acupuncture at HT7 regulates immobility and 22-kHz USVs via Sigma1 R in the VTA upon acute ETOH exposure, which have similarities with IP injection of BD 1047 (10 mg/kg).
Abstract: Background Most ETOH addiction preclinical studies have focused on the rewards of chronic ETOH self-administration or the ETOH reinstatement model. Acute ETOH administration studies are scarce despite the potential of ETOH to cause sedation, intoxication and reduced acute functional tolerance. Here, we established a rat model of acute ETOH administration induced by an intraperitoneal injection of 1 g/kg ethanol and assessed the similarities in physiological and behavioral effects between acupuncture and Sigma1 R antagonists. Methods Male Wistar rats (300-330 g) received pretreatment with (1) saline injection, (2) saline + mechanical stimulation using a mechanical acupuncture instrument (MAI) for acupuncture at the Shenmen (HT7), (3) ETOH (1 g/kg) injection, (4) ETOH + HT7, or (5) the selective σ1 R antagonist BD 1047 (3, 10, or 30 mg/kg, intraperitoneal (IP) injection). ETOH (1 g/kg) or saline was IP injected after 10 min. Then, ETOH-induced immobility was evaluated in an open field arena, ultrasonic vocalizations (USVs) indicating ethanol-induced emotional changes were recorded in a recording chamber, and the rats were sacrificed for the analysis of protein levels of σ1 R in several regions of the brain. Results Acute ethanol exposure increased the immobile time, 22-kHz USVs, and protein levels of σ1 R in the ventral tegmental area (VTA). However, pretreatment with acupuncture at HT7 induced recovery of immobile time, reduced 22-kHz USVs, and regulated the protein levels of σ1 R in the VTA. These effects have similarities with IP injection of BD 1047 (10 mg/kg). Conclusion This study showed that acupuncture at HT7 regulates immobility and 22-kHz USVs via Sigma1 R in the VTA upon acute ETOH exposure.