apelin-13-peptide and Inflammation

Apelin/APJ is widely distributed in various tissues in the body and participates in the regulation of physiological and pathological mechanisms such as autophagy, apoptosis, inflammation, and oxidative stress. Apelin-13 is an adipokine family member with multiple biological roles and has been shown to be involved in the development and progression of bone diseases. In the process of osteoporosis and fracture healing, Apelin-13 plays an osteoprotective role by regulating the autophagy and apoptosis of BMSCs, and promotes the osteogenic differentiation of BMSCs. In addition, Apelin-13 also attenuates the progression of arthritis by regulating the inflammatory response of macrophages. In conclusion, Apelin-13 has an important connection with bone protection, which provides a new strategy for the clinical treatment of bone-related diseases.

Topics: Apelin Receptors; Apoptosis; Autophagy; Humans; Inflammation; Osteogenesis

Acute kidney injury (AKI) is observed in nearly 60% of patients undergoing cisplatin (CP) therapy. The aim of this study was to reveal the potential effects of apelin-13 (AP-13) in the prevention of CP-induced renal toxicity, together with its antioxidant and anti-inflammatory effect mechanisms. Four experimental groups were established. Group 1, the control group, received 0.9% saline solution alone intraperitoneally (IP). Group 2, the CP group, received CP IP at 5 mg/kg once weekly for four weeks for induction of nephrotoxicity. In Group 3, the CP + Apelin-13 (AP-13) group, AP-13 was prepared at 20 nmol kg/d in sterile pyrogen-free saline before injection every day for four weeks and administered IP. CP was administered IP at 5 mg/kg once weekly for four weeks for induction of nephrotoxicity. In Group 4, the AP-13 group, AP-13 was prepared at 20 nmol kg/d in sterile pyrogen-free 0.9% saline before injection every day for four weeks and administered IP. Thiobarbituric acid reactive substances (TBARS), thiol (-SH), interleukin-1 beta, cleaved caspase-3, 8-hydroxy 2-deoxyguanosine (8-OHdG), and nuclear factor kappa B (NF-κβ/p65) levels were then measured. Increased oxidative stress, inflammation, and apoptosis as a result of CP application activated the cascade. However, AP-13 administration reduced the oxidative stress increased by CIS with the determined antioxidant effect and reduced the damage by increasing total -SH levels. 8-OHdG and NF-κβ/p65, which were up-regulated by triggering oxidative stress and inflammation, were down-regulated through the antioxidant and anti-inflammatory effects of AP-13.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Cisplatin; Inflammation; Kidney; Oxidative Stress; Rats

Apelin-13 is an endogenous adipocytokine known for its antioxidant, antiinflammatory, and antiapoptotic properties.. We aimed to investigate the possible protective effects of exogenous Apelin-13 administration on oxidative stress, inflammation, and apoptosis induced by the cytotoxic agent cyclophosphamide (CP) in the lungs.. Twenty-four male Wistar albino rats were divided into four groups: Control (saline), CP (200 mg/kg), Apelin-13 (10 μg/kg/day), and CP+Apelin-13. CP was administered as a single dose on the fifth day, and apelin-13 was administered intraperitoneally for five days. Total oxidant status (TOS), total antioxidant status (TAS), and lipid peroxidation were determined with spectrophotometry, TNFα and IL1β were determined with ELISA, APJ, Sirt1, NF-κB, and p53 mRNA expressions were determined with qRT-PCR, cytochrome (Cyt) C and caspase-3 protein expressions were studied with western blotting in lung tissues. The oxidative stress index (OSI) was also calculated. Furthermore, serum surfactant protein-D (SP-D) and Krebs von den Lungen-6 (KL-6) levels were measured with ELISA.. Compared to the control group, TOS, OSI, lipid peroxidation, TNFα, IL1β, cyt C, caspase-3, APJ, NF-κB, and p53 were higher, and Sirt1 was lower in the lung tissue of rats in the CP group. Serum KL-6 and SP-D levels were higher in the CP group. Co-administration of CP with Apelin-13 completely reversed the changes induced by CP administration.. Exogenous Apelin-13 treatment protected lung tissue against injury by inhibiting cyclophosphamide-induced oxidative stress, inflammation, and apoptosis. This protective effect of apelin-13 was accompanied by upregulation of the Sirt1 and downregulation of NF-κB/p53 in the lungs.

Topics: Animals; Antioxidants; Apelin; Apoptosis; Caspase 3; Cyclophosphamide; Inflammation; Lung; Male; NF-kappa B; Oxidative Stress; Pulmonary Surfactant-Associated Protein D; Rats; Rats, Wistar; Sirtuin 1; Tumor Necrosis Factor-alpha; Tumor Suppressor Protein p53

Early brain injury (EBI) has been considered as the major contributor to the neurological dysfunction and poor clinical outcomes of subarachnoid hemorrhage (SAH). Studies showed that apelin-13 exhibits a neuroprotective effect in brain damage induced by cerebral ischemia. However, it remains unclear whether apelin-13 could exhibit the protective functions following SAH. The present study aimed to validate the neuroprotective role of apelin-13 in SAH, and further investigated the underlying mechanisms.. We constructed SAH rat model and we found that apelin-13 significantly alleviated neurological disorder and brain edema, improved memory deficits in SAH rats. Apelin-13 treatment decreased contents of TNF-α and IL-1β in cerebral spinal fluid of SAH rat by using ELISA. Apelin-13 treatment promoted the expression of APJ and Bcl-2, and decreased the level of active caspase-3 and Bax in the temporal cortex after SAH by using western blot. Also, apelin-13 attenuated the cortical cell death and neuronal degeneration as shown by TUNEL, FJB and Nissl staining. However, ML221, an inhibitor of APJ, significantly reversed all the above neuroprotective effects of apelin-13. Moreover, a neuron-microglia co-culture system, which mimic SAH in vitro, confirmed the protective effect of apelin-13 on neurons and the inhibitory effect on inflammation through apoptosis-related proteins.. These data demonstrated that apelin-13 exhibit a neuroprotective role after SAH through inhibition of apoptosis in an APJ dependent manner.

Topics: Animals; Apoptosis; Brain Injuries; Inflammation; Intercellular Signaling Peptides and Proteins; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Subarachnoid Hemorrhage

The precise mechanisms whereby apelin-13 acts against ischemic stroke have remained in the dark. Hence, this study aims to examine the effects of apelin-13 on hypothalamic-pituitary-adrenal (HPA) axis over activation, Jak2-STAT3 signaling pathway, and inflammation following ischemic stroke.. Middle cerebral artery occlusion (MCAO) was used to induce the cerebral ischemic/reperfusion injury (I/RI). Thirty-five male Wistar rats (250-300 g, 8 weeks old) were randomly divided into sham, MCAO, and intravenous (IV) apelin-13 treated groups which received 10, 20, and 40 µg/kg 5 min before reperfusion (n = 7). Neurological status (modified Longa scoring scale), infarct volume, serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), interleukin 6 (IL-6), corticosterone, and the expressions of the Jak2/STAT3 were assessed.. Our results confirm that IV administration of all three doses of apelin-13 significantly improved neurological defects and reduced infarct volume following cerebral I/RI. Furthermore, we observed that acute stroke caused a rise in the expression of the Jak2/STAT3, IL-6, corticosterone, and MDA content, while apelin-13 could reduce the expression of the Jak2/STAT3 and the serum indices in a dose-dependent manner. The 40 µg/kg dose of apelin-13 was also more effective in reducing the infarct volume and improving TAC.. Our findings suggest that apelin-13 has protective effects against cerebral I/RI-related inflammation and also could attenuate the HPA axis over activation.

Topics: Animals; Brain Ischemia; Corticosterone; Hypothalamo-Hypophyseal System; Infarction, Middle Cerebral Artery; Inflammation; Interleukin-6; Ischemic Stroke; Janus Kinase 2; Male; Pituitary-Adrenal System; Rats; Rats, Wistar; Reperfusion Injury; Signal Transduction

Apelin and its receptor angiotensin receptor - like 1 (APJ) are closely related to renal fibrosis, but their specific roles in renal fibrosis are still controversial. In this article, we discussed the role of Apelin/APJ system in renal fibrosis and its mechanism.. Chronic intermittent hypoxia (CIH) rat model was established to induce the environment of renal fibrosis and a competitive antagonist of the APJ receptor ML221 was administered to CIH rats. The rats were divided into Control, CIH and ML221 groups. HE staining was used to detect the inflammatory injury and fibrosis of renal tissue. The expressions of renal fibrosis-related indicators transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA) and Human type I collagen (Col-Ⅰ) were detected by immunohistochemistry. The levels of oxidative stress indexes reactive oxygen species (ROS), Malondialdehyde (MDA), Superoxide Dismutase (SOD) and inflammation-related indexes Interleukin (IL) -6, tumor necrosis factor-α (TNF-α) and IL-1β were detected by ELISA. At the same time, the levels of Apelin-13 and AngiotensinII (AngⅡ) were also measured by ELISA. Finally, western blot was used to detect the expression of Apelin pathway and renal fibrosis-related proteins. In addition, at the cellular level, we divided the cells into Control, CIH, Apelin-13 and Apelin-13+ML-221 groups to further verify the specific mechanisms at the cellular level.. The expression of Apeline-13 and its related pathways was significantly increased after the induction of CIH in rats. However, the degree of renal fibrosis in ML221 group was further significantly increased after inhibiting the expression of Apelin. At the cellular level, CIH model cells treated with Apelin-13 significantly reduced cell proliferation, oxidative stress and inflammatory response, and decreased the expression of fibrosis-related proteins, which can be reversed by ML221 administration.. The increased reactivity of Apelin may be one of the protective mechanisms against renal fibrosis induced by CIH.

Topics: Angiotensin II; Animals; Apelin; Apelin Receptors; Cell Line; Fibrosis; Humans; Hypoxia; Inflammation; Intercellular Signaling Peptides and Proteins; Kidney; Kidney Diseases; Male; Nitrobenzoates; Oxidative Stress; Pyrans; Rats, Wistar

It has been shown that alcohol consumption by pregnant women can have detrimental effects on the developing fetus and lead to fetal alcohol spectrum disorders (FASD). Exposure to alcohol in rat pups during this period causes long-term changes in the structure of the animal's hippocampus, leading to impaired hippocampal-related brain functions such as navigation tasks and spatial memory. Apelin-13, a principal neuropeptide with inhibitory effects on neuroinflammation and brain oxidative stress production, has beneficial properties on memory impairment and neuronal injury. The protective effects of apelin-13 have been evaluated on ethanol-related neurotoxicity in the hippocampus of rat pups. Rat pups from 2 until 10 postnatal day, similar to the third trimester of pregnancy in humans, were intubated total daily dose of ethanol (5/27 g/kg/day). Immediately after intubation, 25 and 50 μg/ kg of apelin-13 was injected subcutaneously. By using Morris water maze task, the hippocampus- dependent memory and spatial learning were evaluated 36 days after birth. Then, Immunohistochemical staining was done to determine the levels of GFAP and caspase-3. ELISA assay was also performed to measure both TNF-α and antioxidant enzymes levels. The current study demonstrates that administration of apelin-13 attenuates spatial memory impairment significantly (P < 0.001). After ethanol neurotoxicity, apelin-13 could also increase the catalase level (P < 0.001), activity of total superoxide dismutase as well as glutathione concentration noticeably (P < 0.05). Other impacts of it could be mentioned as attenuating TNF-α production and also preventing lipid peroxidation (P < 0.001). In addition, the results showed that the level of GFAP as a neuroinflammation factor and the number of active caspase-3 positive cells can be decreased by apelin-13 (P < 0.01). Regarding the protective effects of apelin-13 against ethanol-induced neurotoxicity, it is a promising therapeutic choice for FASD; but more studies are needed.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Brain Chemistry; Drug Evaluation, Preclinical; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Glial Fibrillary Acidic Protein; Hippocampus; Inflammation; Intercellular Signaling Peptides and Proteins; Lipid Peroxidation; Male; Memory Disorders; Models, Animal; Morris Water Maze Test; Nerve Tissue Proteins; Oxidative Stress; Pregnancy; Random Allocation; Rats; Rats, Wistar; Spatial Learning; Tumor Necrosis Factor-alpha

Apelin-13 and APJ are implicated in different key physiological processes. This work aims at exploring the radioprotective effect of fucoxanthin (FX) on γ-radiation (RAD)-induced changes in the apelin-13/APJ pathway, which causes damage in the liver, kidney, lung and spleen of mice. Mice were administered FX (10 mg kg-1 day-1, i.p) and exposed to γ-radiation (2.5 Gy week-1) for four consecutive weeks. The treatment of irradiated mice by FX resulted in a significant amendment in protein expression of the apelin-13/APJ/NF-κB signalling pathway concurrently with reduced hypoxia (hypoxia-inducible factor-1α), suppressed oxidative stress marker (malondialdehyde), enhanced antioxidant defence mechanisms (reduced glutathione and glutathione peroxidase), a modulated inflammatory response [interleukin-6 (IL-6), monocyte chemoattractant protein-1, IL-10 and α-7-nicotinic acetylcholine receptor) and ameliorated angiogenic regulators [matrix metalloproteinase (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-1), as well as the tissue damage indicator (lactate dehydrogenase) in organ tissues. In addition, there were significant improvement in serum inflammatory markers tumour necrosis factor-α, IL-10, IL-1β and C-reactive protein compared with irradiated mice. The histopathological investigation of the FX + RAD organ tissues support the biochemical findings where the improvements in the tissues' architecture were obvious when compared with those of RAD. FX was thus shown to have a noticeable radioprotective action mediated through its regulatory effect on the apelin-13/APJ/NF-κB signalling pathway attributed to its antioxidant and anti-inflammatory activity that was reflected in different physiological processes. It could be recommended to use FX in cases of radiation exposure to protect normal tissues.

Topics: Animals; Antioxidants; Apelin Receptors; Gamma Rays; Inflammation; Intercellular Signaling Peptides and Proteins; Kidney; L-Lactate Dehydrogenase; Liver; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; NF-kappa B; Organ Specificity; Oxidants; Signal Transduction; Tissue Inhibitor of Metalloproteinase-1; Whole-Body Irradiation; Xanthophylls

Cardiovascular diseases are the leading causes of mortality in patients with chronic kidney disease. Nitric oxide has a critical role in both endothelial dysfunction and the atherosclerosis process. We aimed to investigate the relationships between serum asymmetric dimethyl arginine (ADMA), LOX-1, and Apelin-13 levels, which are known to act over nitric oxide with endothelial dysfunction and cardiac morphology as well as with each other in hemodialysis patients. The study comprised a total of 120 patients (53 females and 67 males) receiving hemodialysis three times a week for at least 6 months and an age-gender matched control group (55 females and 58 males). Serum ADMA, LOX-1, and Apelin-13 levels were measured using the ELISA technique. Echocardiography, 24-h blood pressure monitoring by the Holter and carotid artery intima-media thickness (CIMT) measurement was performed on all of the included subjects. The associations between serum ADMA, LOX-1, and Apelin-13 levels with CIMT, echocardiographic parameters [left ventricular mass (LVM) and left ventricular mass index (LVMI)], and inflammatory markers [high sensitive C-reactive protein (hsCRP) and neutrophil lymphocyte ratio (NLR)] were evaluated by correlation analysis. Serum ADMA, Apelin-13, and LOX-1 levels were significantly higher in the hemodialysis group than the controls (P < 0.001, P < 0.001, and P < 0.001, respectively). CIMT, hsCRP, and NLR levels were also significantly higher in the hemodialysis group (P < 0.05, P < 0.001, P < 0.001, respectively). Significant correlations were observed among the serum ADMA, Apelin-13, and LOX-1 levels. Moreover, notably positive correlations were found between these three biochemical markers and LVM, LVMI, hsCRP, and CIMT. Serum ADMA, Apelin-13, and LOX-1 levels can be indicators not only for the inflammatory process but also for the pathogenesis of cardiovascular diseases in hemodialysis patients.

Topics: Arginine; Biomarkers; C-Reactive Protein; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Lymphocytes; Male; Middle Aged; Neutrophils; Renal Dialysis; Scavenger Receptors, Class E