Exogenous Apelin-13 Administration Ameliorates Cyclophosphamide- Induced Oxidative Stress, Inflammation, and Apoptosis in Rat Lungs.

BACKGROUND: Apelin-13 is an endogenous adipocytokine known for its antioxidant, antiinflammatory, and antiapoptotic properties. OBJECTIVE: 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. METHODS: 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 IL1ß 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. RESULTS: Compared to the control group, TOS, OSI, lipid peroxidation, TNFα, IL1ß, 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. CONCLUSION: 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.

Effect of omentin on cardiovascular functions and gene expressions in isolated rat hearts.

OBJECTIVE: Omentin is a recently identified novel adipocytokine mainly expressed in the epicardial adipose tissue. Although it has favorable effects on cardiovascular disease, the impact of omentin on the hearts is still an understudied issue. The aim of the present study was to investigate the possible effects of omentin on isolated rat heart. METHODS: Using the Langendorff method, 28 adult male Sprague-Dawley rat hearts were isolated and perfused with modified Krebs-Henseleit solution (mK-Hs). Concentrations of 100, 200, and 400 ng/mL omentin were given to the hearts for 30 min. The control group (n=7) was perfused with mK-Hs alone. Gene expressions in the left ventricle tissue were determined by real-time polymerase chain reaction. Left ventricular cyclic adenosine monophosphate and cyclic guanosine monophosphate (cGMP) concentrations were determined by using enzyme-linked immunosorbent assay. RESULTS: All concentrations of omentin significantly decreased left ventricular developed pressure and maximal rate of pressure development that are the indexes of cardiac contractility. At the same time, omentin decreased both phosphoinositide 3-kinase γ (PI3Kγ) and sarcolemmal L-type Ca2+ channel (CaV1.2) mRNA levels. Moreover, this peptide at concentrations of 200 and 400 ng/mL increased endothelial nitric oxide synthase (eNOS) mRNA. Furthermore, concentrations of 200 and 400 ng/mL omentin increased the amount of cGMP. CONCLUSION: We conclude that acute omentin treatment decreases cardiac contractility. Elevated eNOS mRNA and cGMP levels with reduced CaV1.2 mRNA are likely to lead to negative inotropy.

Erythropoietin Protects the Kidney by Regulating the Effect of TNF-α in L-NAME-Induced Hypertensive Rats.

BACKGROUND/AIMS: Hypertension is the leading cause of death worldwide. Chronic high blood pressure induces inflammation. Tumor necrosis factor (TNF)-α plays a major role in inflammation and also depresses the synthesis of erythropoietin, which exerts protective effects on tissue; however, the mechanism is still unclear. We investigated the protective effect of erythropoietin against tissue damage caused by hypertension in the kidney and whether this effect was suppressed by TNF-α. METHODS: First, we detected the optimum chronic dose for darbepoetin-α (Depo), which is a long-acting erythropoietin analog for rats. We separated 60 female adult rats into 6 groups: control, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), L-NAME+Depo, L-NAME+Remicade (an anti-TNF-α antibody), L-NAME+Depo+Remicade, Depo, and control. After 1 month of treatment, we measured cardiovascular parameters, took blood samples, sacrificed the rats, and removed kidneys for analyses. RESULTS: The apoptotic index and the plasma and kidney mRNA levels of TNF-α increased in the L-NAME group and decreased in all other treatment groups. Macrophage accumulation increased in the L-NAME and L-NAME+Remicade groups, while it decreased in the Depo group. The mRNA abundance of TNF receptor 1 (TNFR1) decreased slightly in the Depo group and TNFR2 increased significantly in the same group. CONCLUSION: Erythropoietin protects kidney tissue against hypertension by preventing the apoptotic effects of TNF-α by blocking macrophage accumulation, decreasing TNF-α levels, and switching the TNF-α receptors from the apoptotic receptor TNFR1 to the proliferative receptor TNFR2.