Beneficial effects of swimming and pomegranate juice in rats with hypertension: A possible role of serum adropin.

Hypertension, characterized by persistent and uncontrolled high blood pressure, is one of the most common significant causes of mortality worldwide. Lifestyle modifications such as exercise and antioxidant intake have showed beneficial effects on hypertensive conditions. Adropin and endothelin-1 (ET-1) have important vasoregulatory functions in the endothelium. However, the underlying mechanisms linking exercise- and/or antioxidant intake-mediated improvement of hypertension are not fully understood. In this study, it was hypothesized that swimming exercise and pomegranate juice (PJ) (as an antioxidant) administration might have protective effects on hypertension development and possible involvements of serum adropin and ET-1. To test the hypothesis, the rats with hypertension, induced by Nω-nitro-L-arginine methyl ester hydrochloride, were subjected to swimming exercise and received PJ for 8 weeks. Weekly systolic and diastolic pressures, serum concentrations of adropin and ET-1, and oxidant/antioxidant parameters in various tissues were measured. The obtained data show that swimming exercise leads to complete protection against hypertension within the 8-week duration, whereas the PJ administration causes an ameliorative effect. In addition, the combination of swimming exercise and PJ administration do not have additive effects in protection against hypertension. Notably, the 8-week swimming exercise restores the diminished serum adropin concentration in rats with hypertension to the control level. Serum adropin significantly correlated with systolic and diastolic pressures, depending on swimming exercise, but not PJ administration. Serum ET-1 concentration inconsistently fluctuates in response to Nω-nitro-L-arginine methyl ester hydrochloride, swimming exercise, and PJ intake. In addition, swimming exercise and/or PJ administration lead to a complete normalization in liver malondialdehyde concentrations of rats with hypertension, whereas these interventions cause slight or no improvements in superoxide dismutase, catalase, and glutathione in the heart, liver, and kidney. In conclusion, 8-week swimming exercise modulates hypertension, possibly by influencing adropin concentration and oxidative stress.

Protective effect of vitamin D on imidacloprid-induced testicular injury in rats.

Introduction: The degenerative effects of imidacloprid via oxidative stress are known. Irisin is a recently discovered peptide with energy regulator and antioxidant effects. In addition, the antioxidant potential of Vitamin D has been reported in previous studies. The current study was performed to investigate the effect of Vitamin D on testis morphology and irisin immunoreactivity in imidacloprid-treated rats. Material and methods: Thirty-two Wistar albino male rats were divided into groups: control (n = 6), corn oil (n = 6), Vitamin D (n = 6), imidacloprid (n = 7) and imidacloprid + Vitamin D (n = 7). Testis tissues were used to evaluate the histopathological, biochemical and immunohistochemical changes. Oxidative state in testis tissue was determined with total antioxidant and oxidant status markers, total antioxidant status (TAS) and total oxidant status (TOS) respectively. Results: In microscopic examination, degenerative changes in the seminiferous tubule epithelium, interstitial edema and increased irisin immunoreactivity were observed in animals given imidacloprid. Also increased TOS and decreased TAS levels were measured in these animals. It was observed that Vitamin D improved the testicular damage histopathologically when compared to the imidacloprid group. However, increase in TAS levels and decrease in both TOS levels and irisin immunoreactivity were found insignificant in animals given Vitamin D. Conclusions: In the present study it was observed that Vitamin D ameliorated testis injury caused by imidacloprid. Furthermore, imidacloprid was found to increase the immunoreactivity of irisin. In the light of our findings, we conclude that the use of Vitamin D could be beneficial against testicular damage caused by imidacloprid.

Effect of light intensity on the tear production, central corneal thickness, and intraocular pressure in broiler chickens.

OBJECTIVE: The objective of the present study was to examine the effect of different light intensities on tear production, corneal thickness, and intraocular pressure in broilers. ANIMALS STUDIED: Both eyes of 72 male broilers were evaluated in this study. MATERIALS AND METHODS: Broilers were divided into the following three groups: low light intensity (n = 24, 5 lux), moderate light intensity (n = 24, 20 lux), and high light intensity (n = 24, 80 lux). The eyes of all birds (n = 72) underwent a complete ophthalmic examination, which included the Schirmer tear test (STT-I), intraocular pressure (IOP), and the central cornea thickness measurement (CCT). The effect of light intensity on the Schirmer test, intraocular pressure, and central corneal thickness values was examined at eye and animal level (right and left eyes separately and cumulatively/no distinguishing left or right) by using one-way ANOVA. RESULTS: At the animal level, without discrimination of left and right eye measurements, statistically significant differences were found between 5-20 and 20-80 lux groups on IOP measurements (p < .05). The difference in CCT measurements between the 5 and 20 lux groups was statistically significant (p < .05), and the corneal thickness of the 5 lux group animals was found to be statistically significant and higher than the 20 lux group (p < .05). CONCLUSIONS: In conclusion, light intensity has an influence on eye health in broilers. Present results may attribute to the future studies as a reference value for broilers raised under different light intensities.

Ameliorative effects of garlic oil on FNDC5 and irisin sensitivity in liver of streptozotocin-induced diabetic rats.

OBJECTIVES: This study was aimed to investigate the effects of garlic oil (GO), an important natural constituent used in alleviating diabetes and its complications, on the expression levels of irisin and related genes. METHODS: Thirty-two rats were divided into four groups: Control, Diabetes-Control, Diabetes+GO 100 mg/kg/day and Control+GO 100 mg/kg/day for 45 days. The measurements included: changes in liver Peroxisome proliferator-activated receptor-gamma-coactivator (PGC)-1α, Fibronectin Type-III-Domain-Containing5 (FNDC5), irisin expression, mRNA expression of p38 and TNF-α (Tumour necrosis factor-α), total-antioxidant-status (L-TAS; S-TAS), total-oxidant-status (L-TOS; S-TOS) in liver and serum, respectively. KEY FINDINGS: There was a significant reduction in serum levels of irisin and S-TAS and expression of PGC-1α and FNDC5 in liver in Diabetes-control compared to Control-group, while a significant increase in serum levels of fasting blood glucose (FBG) and TOS, also p38 and TNF-α expressions in liver. In Diabetes+GO group, there was a significant increase in serum irisin and S-TAS, also expression of PGC-1α and FNDC5 in liver, while serum FBG, S-TOS levels, and mRNA expression of p38 and TNF-α in liver were decreased compared to Diabetes-control group (P < 0.05). CONCLUSIONS: GO alleviated the diabetic liver injury by decreasing Oxidative-Stress parameters and regulation PGC-lα, FNDC5, irisin and P38, keeping the balance of TAS/TOS and TNF-α.

Effects of N-acetylcysteine on kidney tissue, matrix metalloproteinase-2, irisin and oxidative stress in a diabetes mellitus model.

DM mellitus (DM) is a prevalent chronic disease; diabetic nephropathy (DN) is a primary cause of chronic kidney disease. Oxidation, energy imbalance, and enzyme and cytokine changes contribute to the development and progression of DN. We investigated the possible effects of the antioxidant, N-acetylcysteine (NAC), on kidney morphology, apoptosis, matrix metalloproteinase-2 (MMP2) activity, irisin levels and oxidative stress in an experimental DM model. We used four equal groups of Wistar albino male rats: control, DM, DM + NAC and NAC. Kidney tissues were evaluated for oxidation state, MMP-2, irisin, caspase-3 and histopathology. In the DM group, total oxidant status level, MMP-2 and caspase-3 immunoreactivity were increased, irisin immunoreactivity and total antioxidant status (TAS) were decreased and histological damage was evident. In the DM + NAC group, all changes were significantly improved. NAC exhibited protective effects against DN.

Effects of cannabinoid receptor 2 synthetic agonist, AM1241, on bleomycin induced pulmonary fibrosis.

Bleomycin (BLM) is a chemotherapeutic agent that can cause pulmonary fibrosis. Little is known about the possible protective role of the CB2 receptor agonist, AM1241. We investigated the effects of CB2 receptor activation by AM1241 on BLM induced lung fibrosis in a rat model. BLM was administered via the trachea. Adult female Wistar rats were divided into five groups: saline (control group), BLM (BLM group), CB2 agonist (AM1241) + BLM (BLMA group), CB2 antagonist (AM630) and CB2 agonist (AM1241) + BLM (BLMA + A group), and vehicle (dimethylsulfoxide) + BLM (BLM + vehicle group). Hydroxyproline, collagen type 1, total protein, glutathione (GSH), malondialdehyde (MDA), interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were measured in lung fibrosis and control tissue using standard methods. We investigated the histopathology of lung tissue to determine the extent of fibrosis. We found significantly higher levels of hydroxyproline, TNF-α, IL-6 and total protein in the BLM group compared to the BLMA group. The level of GSH also was higher in the BLMA group compared to the BLM group. Inflammation and fibrotic changes were significantly reduced in the BLMA group. Our findings suggest that CB2 receptor activation provided protection against BLM induced pulmonary fibrosis by suppressing oxidative stress and increasing cytokines.

Protective effects of benfotiamine on irisin activity in methotrexate-induced liver injury in rats.

INTRODUCTION: Methotrexate (MTX) causes hepatotoxicity by producing oxidative stress. Benfotiamine and irisin have protective effects against oxidative stress. The aim of this study was to investigate the changes in irisin activity in the liver as a result of toxicity produced by MTX and the protective role of benfotiamine in the hepatotoxicity. MATERIAL AND METHODS: Rats were divided into 4 groups as follows: control, benfotiamine (50 mg/kg, oral gavage (o.g.), for 14 days), MTX (MTX 20 mg/kg intraperitoneally (i.p.) on day 1), MTX + benfotiamine (MTX 20 mg/kg (i.p.) on day 1, then 50 mg/kg (o.g.) benfotiamine for 14 days). Liver tissue was used to examine histopathological and immunohistochemical changes. Serum was used to look for oxidative stress markers (total antioxidant status (TAS) and total oxidant status (TOS)). RESULTS: Administration of MTX caused a significant TOS increase and TAS decrease in the serum as compared to the control group. Immunohistochemically, irisin was significantly increased in immunoreactivity in the MTX group as compared to the control group (p < 0.05). Significant histopathological improvement and decrease in serum TOS levels were observed in the MTX + benfotiamine group compared to the MTX group (p < 0.05). In addition, an increase in TAS level and a decrease in irisin immunoreactivity were observed but they were not statistically significant (p > 0.05). CONCLUSIONS: Our results showed that MTX caused an increase in the activity of irisin after producing toxicity in the liver. In addition, we found that benfotiamine was effective in preventing damage caused by MTX in the liver.

The exogenous administration of CB2 specific agonist, GW405833, inhibits inflammation by reducing cytokine production and oxidative stress.

The present study aimed to investigate the role of cannabinoid 2 (CB2) receptors in a rat model of acute inflammation. Therefore, the potential of anti-inflammatory effects of CB2 receptor agonist (GW405833), CB2 receptor antagonist (AM630), and diclofenac, were investigated in carrageenan induced paw oedema in rats: as were assessed by measuring paw oedema; myeloperoxidase (MPO) activity in paw tissue; malondialdehyde (MDA) concentration; glutathione (GSH) level in paw tissue for oxidant/antioxidant balance; cytokine (interleukin-1ß, IL-1ß; tumour necrosis factor-α, TNF-α) levels in serum; histopathology of paw tissue for inflammatory cell accumulations. The results showed that GW405833 or diclofenac significantly reduced carrageenan-induced paw oedema. GW405833 also inhibited the increase of MPO activity, the recruitment of total leukocytes and neutrophils, and MDA concentration during carrageenan-induced acute inflammation, along with reversed nearly to the normal levels the increased of TNF-α, and IL-1ß in serum. AM630 did not affect inflammation alone however clearly reversed the effects of agonist when co-administered. The mechanism of GW405833's suppression of inflammation is supported by these results, which are achieved by the inhibition of neutrophil migration, which regulates the reduction of oxidative stress, TNF-α and IL-1ß levels. Finally, the activation of CB2 receptor, by selective agonist, has a major role in peripheral inflammation, and in the near future, targeting the peripheral cannabinoid system as a promising alternative to treat inflammation diseases may be considered a novel pharmacologic approach.

Hepatoprotective properties for Salvia cryptantha extract on carbon tetrachloride-induced liver injury.

The present study was designed to determine the possible hepatoprotective effects of Salvia cryptantha (black weed) plant extract against carbon tetrachloride (CCl4)-induced hepatic injury in rats. Animals were grouped as follows: control group (Group I), CCl4 group (Group II), olive oil group (Group III), CCl4 + S. cryphantha 200 mg/kg group (Group IV), and CCl4 + S. cryptantha 400mg/kg group (Group V). Rats were injected intraperitoneally with CCl4 diluted in olive oil (50% v/v) at a dose of 1ml/kg body weight.  Bax and Caspase3 were determined by immunohistochemical staining, while apoptotic index was evaluated using TUNEL assay. Total mRNA was isolated from liver tissues, and the levels of BCL2, Caspase3, SOD, CAT, and glutathione peroxidase (GPx) were determined by using PCR, while MDA level were determined using a colorimetric assay. The antioxidant and anti-apoptotic gene transcripts were decreased in all of the control and treatment groups, while Caspase3 levels were not statistically different. The S. cryptantha plant extract treatment was also found to improve SOD, GPx, and catalase levels, while reducing the serum levels of MDA. The extract of S. cryptantha supplementation had a protective effect against CCl4-induced liver damage. S. cryptantha extract as a supplement may be useful as a hepato-protective agent to combat the toxic effects caused by CCl4 and other chemicals.

Effect of sugammadex on rocuronium induced changes in pancreatic mast cells.

Mast cells play a vital role in hypersensitivity reactions. Rocuronium is known to cause mast cell mobilization, hypersensitivity, and pancreatitis. The aim of this study was to investigate the effects of sugammadex on pancreatic changes due to rocuronium. A total of 42 Sprague-Dawley male rats were divided into six equal groups to receive either rocuronium 1 mg/kg intravenously (i.v., R group), rocuronium 1 mg/kg + sugammadex 16 mg/kg i.v. (RS16 group), rocuronium 1 mg/kg + sugammadex 96 mg/kg i.v. (RS96 group), sugammadex 16 mg/kg (S16), sugammadex 96 mg/kg i.v. (S96 group), or 0.9% sodium chloride (control group). Sugammadex was administered 5s later following rocuronium. In R group, mast count was higher, and the distribution rate of granules and nuclear changes were different compared with other groups. Distribution rate of granules in groups S16 and S96 were similar to the control group and lower compared with other groups. The amount of mast cells and granule density in groups RS16 and RS96 was lower compared with R group. The amount of mast cells in groups RS16 and RS96 was significantly lower compared with other treatment groups. These results suggest that sugammadex may have an inhibitory effect on mobilization and morphological changes in pancreatic mast cells induced by administration of rocuronium and sugammadex in rats.

The effect of rocuronium, sugammadex, and their combination on cardiac muscle and diaphragmatic skeletal muscle cells.

PURPOSE: Rocuronium has been associated with muscle weakness when administered in prolonged infusions. The effect of sugammadex and rocuronium together on muscle is unknown. In this study, we examined the effects of rocuronium and sugammadex, and the complex formed by these agents, on cardiac and diaphragmatic muscle cells. METHODS: Forty-two Sprague-Dawley male rats were divided into six groups. Group I received only rocuronium at a dose of 1 mg/kg and groups II and III received sugammadex alone at doses of 16 and 96 mg/kg, respectively. Groups IV and V received 1 mg/kg rocuronium plus 16 mg/kg sugammadex and 1 mg/kg rocuronium plus 96 mg/kg sugammadex, respectively. Group six was the control group and received only 0.9 % NaCl without any drug. RESULTS: Histopathological examination demonstrated that rocuronium and high doses of sugammadex accumulated in both cardiac and diaphragm muscle tissues. We also observed intense edema and degeneration in diaphragmatic and myocardial cells when the rocuronium-sugammadex complex was used. Rocuronium and sugammadex remain in the circulation for a long time and they may cause skeletal muscle myopathy, vacuolization, pyknotic nuclear clumps, and hypertrophy, and weaken the muscle fibers. CONCLUSION: Rocuronium, sugammadex, and rocuronium-sugammadex complexes cause histopathological changes and immunoreactivity to calcineurin in muscle cells.