Effects of Vitamin D on Asprosin Immunoreactivity Against Cyclophosphamide-Induced Liver Injury in Rats.

Background Cyclophosphamide (CP), commonly used as an anticarcinogenic drug, has the potential to induce detrimental effects on multiple tissues, including the liver. Asprosin, which is a glucogenic adipokine, induces the liver to secrete glucose, thus contributing to the maintenance of homeostasis. This study aims to investigate the immunoreactivity of asprosin in the liver tissue of rats exposed to CP administration, as well as the changes in its levels due to the supplementation of Vitamin D (Vit D). Materials and methods Four experimental groups were formed, including control, Vit D (200 IU/kg), CP (200 mg/kg), and Vit D+ CP. Histopathological analysis was carried out by employing staining methods on liver tissues. These techniques encompassed the application of hematoxylin-eosin (H&E), Masson's trichrome, and periodic acid Schiff (PAS). Through the application of spectrophotometric methods, concentrations of malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS), and asprosin were determined. Furthermore, apoptotic cells were identified by the terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) method, and the asprosin immunoreactivity was determined by immunohistochemistry. Results Under light microscope examination, the histopathological damage was found to be more notable in the CP group compared to the control group. Moreover, a decrease was observed in serum and tissue asprosin levels, while an increase was noted in the count of apoptotic cells, along with elevated MDA and TOS levels. However, in the CP+Vit D group, Vit D administration alleviated histopathological damage. Notably, there were significant increases in TAS and asprosin levels, accompanied by reductions in both MDA and TOS levels. Conclusions The effect of CP on liver tissue was observed to result in damage and a reduction in asprosin levels. Vit D supplementation revealed elevated asprosin levels and a distinct protective effect on the tissue. Considering the association between asprosin and liver injury induced by CP, further research is needed to elucidate the mechanisms that underlie the effect of asprosin on tissues. When combined with Vit D, asprosin holds promise for potential clinical applications as a therapeutic target.

The Effects of N-acetylcysteine on Transient Receptor Potential Melastatin 2 Channels Activation and Expression in Testicular Tissue of Diabetic Rats.

INTRODUCTION: Diabetes mellitus (DM) is a common, chronic metabolic disease that has harmful effects on many diverse tissues, including the testis. One of the ways of tissue damage is the modification of transient receptor potential melastatin 2 (TRPM2) channels by increased reactive oxygen species (ROS). In our study for the first time, it was aimed to investigate TRPM2 channel activation in testicular tissues of diabetic rats induced by streptozotosin (STZ) and to examine the efficacy of N-acetylcysteine (NAC) treatment, which is an antioxidant. METHODS: In our study, 28 Wistar albino male rats aged 8-10 weeks were used, and animals were divided into four groups: control group, NAC group, DM group, and DM + NAC group. The experimental phase was designed as eight weeks. The malondialdehyde (MDA) level, which is an indicator for lipid peroxidation due to oxidative stress, was measured by the spectrophotometric method. The Tunel assay was used to determine apoptosis on testicular tissue. TRPM2 immunoreactivity was determined by the avidin-biotin-peroxidase complex method, and quantitative polymerase chain reaction (QPCR) was used to determine TRPM2 expression levels. RESULTS: It was seen that MDA levels were significantly increased in the DM group and decreased after NAC treatment. Similarly, it was observed that apoptosis levels, which increased significantly in diabetic rats, decreased to the levels of the control group after treatment. It was seen that TRPM2 activation and expression levels were significantly decreased in the DM group. CONCLUSION:  The results of this study show that NAC regulates TRPM2 activation in the testicular tissue of patients with diabetes and has tissue-protective properties.

Unraveling Molecular Fingerprints of Catalytic Sulfur Poisoning at the Nanometer Scale with Near-Field Infrared Spectroscopy.

Fundamental understanding of catalytic deactivation phenomena such as sulfur poisoning occurring on metal/metal-oxide interfaces is essential for the development of high-performance heterogeneous catalysts with extended lifetimes. Unambiguous identification of catalytic poisoning species requires experimental methods simultaneously delivering accurate information regarding adsorption sites and adsorption geometries of adsorbates with nanometer-scale spatial resolution, as well as their detailed chemical structure and surface functional groups. However, to date, it has not been possible to study catalytic sulfur poisoning of metal/metal-oxide interfaces at the nanometer scale without sacrificing chemical definition. Here, we demonstrate that near-field nano-infrared spectroscopy can effectively identify the chemical nature, adsorption sites, and adsorption geometries of sulfur-based catalytic poisons on a Pd(nanodisk)/Al2O3 (thin-film) planar model catalyst surface at the nanometer scale. The current results reveal striking variations in the nature of sulfate species from one nanoparticle to another, vast alterations of sulfur poisoning on a single Pd nanoparticle as well as at the assortment of sulfate species at the active metal-metal-oxide support interfacial sites. These findings provide critical molecular-level insights crucial for the development of long-lifetime precious metal catalysts resistant toward deactivation by sulfur.

The effects of adalimumab on the rat autotransplantation endometriosis model: A placebo-controlled randomized study.

BACKGROUND: Endometriosis is a chronic inflammatory pathology that can cause persistent pelvic pain and infertility by affecting women of reproductive age. It is defined as the placement of endometrial tissue outside the uterine cavity. Hormonal, genetic and immunological factors have an effect on the development of endometriotic implants. Adalimumab is a monoclonal antibody specific for tumor necrosis factor alpha (TNF-á), used in the treatment of autoimmune diseases. OBJECTIVES: To investigate the effectiveness of adalimumab on histopathological and biochemical values in rats with experimental endometriosis. MATERIAL AND METHODS: This study is a comparative, prospective, experimental rat study. Wistar albino female rats were divided into 4 groups. Group 1 was separated as the control group. Endometriotic implants were simultaneously induced in group 2 and group 3. After 4 weeks, developing endometriotic foci were measured. Adalimumab (5 mg/kg) was simultaneously intraperitoneally (ip.) administered to group 3 and group 4 for 4 weeks. At the end of the study, histopathological scoring and fibrillin-1 scoring were performed. Total antioxidant status (TAS), total oxidant status (TOS) and malondialdehyde (MDA) values were measured. Findings in all groups were compared. RESULTS: When group 1 and group 2 were compared, the histopathological score, as well as MDA and TOS levels increased, while TAS levels decreased in group 2 (p < 0.001). After adalimumab treatment, the average endometriotic implant size in group 3 (0.32 ±0.002 mm) decreased compared to group 2 (0.77 ±0.04 mm) (p = 0.032). While fibrillin-1 score increased in group 2 and group 3 compared to group 1, it decreased in group 3 compared to group 2 (p < 0.001). Histopathological score decreased, TAS levels increased and MDA levels decreased in group 3 compared to group 2 (p < 0.001). CONCLUSIONS: Adalimumab may play a role in the regression of endometrial implants by showing antioxidant and anti-inflammatory effects on histopathological damage and fibrosis.

Effects of N-acetyl cysteine on TRPM2 expression in kidney and liver tissues following malathion intoxication.

We investigated the effects of N-acetyl cysteine (NAC) on transient receptor potential melastatin 2 (TRPM2) channel expression in rat kidney and liver tissues following experimental malathion intoxication. We used seven groups of six male Wistar albino rats: control group, NAC, pralidoxime + atropine, malathion, malathion + pralidoxime + atropine, malathion + pralidoxime + atropine + NAC, and malathion + NAC. Single doses of 100 mg/kg N-acetyl cysteine, 40 mg/kg pralidoxime, 2 mg/kg atropine and 1/3 the lethal dose of malathion were administered. No difference in malondialdehyde (MDA) levels, apoptosis or TRPM2 immunoreactivity was found in liver tissue among the groups. In kidney tissue, MDA levels, apoptosis and TRPM2 immunoreactivity were increased significantly in the malathion and malathion + NAC groups compared to the control group. We found that organophosphate intoxication did not affect MDA, apoptosis or TRPM2 immunoreactivity in rat liver during the acute period. By contrast, we found that in kidney tissue, MDA, apoptosis, and TRPM2 immunoreactivity were increased significantly following administration of malathion. Also, NAC given in addition to pralidoxime and atropine reduced MDA to control levels.

Effects of vitamin B12 on rat ovary with ischemia-reperfusion injury.

We investigated the histopathological and biochemical effects of vitamin B12 on ischemia-reperfusion (I-R) injury using a rat ovarian torsion-detorsion model. We used four groups of female Wistar albino rats. Group 1 (sham group): both ovaries were removed. Group 2 (torsion group): ovarian torsion was established. Group 3 (torsion-detorsion group) perfusion was retored after ischemia for 2 h. Group 4 (torsion-detorsion-vitamin B12 group): after 2 h ovarian torsion, perfusion was re-established and 4 mg/kg vitamin B12 was administered for 2 h. Follicular degeneration, vascular congestion, hemorrhage, edema and infiltration were evaluated histologically. Tissue damage was decreased in group 4 compared to groups 2 and 3. Total antioxidant status TAS), total oxidant status (TOS) and malondialdehyde (MDA) level were measured. The values for TOS and MDA for groups 1 and 4 were similar. We found a significant increase in MDA and TOS levels in group 3 compared to group 2. MDA and TAS levels decreased and TOS levels were increased in group 4 compared to groups 2 and 3. MDA, TAS and TOS values were increased in groups 2 and 3 compared to group 1. We found that vitamin B12 reduced I-R damage in the rat ovary.

Vitamin D improves oxidative stress and histopathological damage in rat ovaries caused by hyperthyroidism.

OBJECTIVE: The aim of this study is to investigate the histopathological and biochemical efficacy of vitamin D on oxidative damage and fibrosis in rat ovaries induced by experimental hyperthyroidism. METHODS: This study is a comparative, prospective experimental rat study. Sprague-Dawley female rats were divided into four groups. Only distilled water was given to the rats in group 1 for 25 days. In group 2, 100 µg/day L-thyroxine was given to rats for 25 days. In Group 3, 100 µg/day L-thyroxine and 200 IU/day vitamin D were given to rats for 25 days. In group 4, only 200 IU/day vitamin D was administered for 25 days. RESULTS: This study is the first to demonstrate the protective effect of vitamin D against ovarian damage caused by experimental hyperthyroidism. Hyperthyroidism caused fibrotic degenerative changes in the ovaries and an increase in the fibrillin 1 score. It caused serum follicle-stimulating hormone (FSH) levels to increase and serum E2 levels to decrease. In addition, malondialdehyde (MDA) and total oxidant status (TOS) levels increased in rats with hyperthyroidism. Vitamin D decreased MDA and TOS values and increased total antioxidant status (TAS) values in rats with hyperthyroidism. It also increased TSH values by causing a decrease in TT3 and TT4 values. It decreased fibrosis, follicle degeneration, stromal degeneration, and fibrillin 1 score in ovarian tissue. CONCLUSION: Vitamin D has positive histopathological and biochemical effects on the oxidative stress and follicle damage caused by hyperthyroidism in ovarian tissue. Human studies with larger case populations should be conducted to evaluate the effects and clinical applications of vitamin D.

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.

Adalimumab Increases Follicle Reserve and Follicle Development in Rat Ovary: The Effect of Adalimumab on Ovarian Reserve.

Introduction Adalimumab is used in the treatment of many chronic inflammatory diseases, especially rheumatoid arthritis. The aim of this experimental study is to determine the histological and biochemical effects of adalimumab on rat ovary. Methods Wistar albino female rats were randomly divided into three groups prior to the experiment: a healthy control group, a 2 mg/kg adalimumab group, and a 5 mg/kg adalimumab group. Then, histopathological findings and biochemical examinations were made in the ovaries of the rats. Hematoxylin-eosin staining, morphometric examination, and Masson trichrome staining were performed. Antimullerian hormone (AMH) levels were measured in the biochemical examination. Results Ovarian follicle count and AMH level were significantly higher in the groups given low-dose adalimumab and high-dose adalimumab (p <0.001). In addition, fibrosis decreased in proportion to the dose of adalimumab (p <0.001). Conclusion Adalimumab is an important biological agent that contributes to the preservation of ovarian function by increasing ovarian follicle reserve and has shown that it can help preserve ovarian reserve in women of reproductive age suffering from chronic inflammatory diseases.

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.

Does alfa lipoic acid prevent liver from methotrexate induced oxidative injury in rats?

PURPOSE: To determine the antioxidant and anti-inflammatory effects of alfa lipoic acid (ALA) on the liver injury induced by methotrexate (MTX) in rats. METHODS: Thirty two rats were randomly assigned into four equal groups; control, ALA, MTX and MTX with ALA groups. Liver injury was performed with a single dose of MTX (20 mg/kg) to groups 3 and 4. The ALA was administered intraperitonealy for five days in groups 2 and 4. The other rats received saline injection. At the sixth day the rats decapitated, blood and liver tissue samples were removed for TNF-α, IL-1β, malondialdehyde, glutathione, myeloperoxidase and sodium potassium-adenosine triphosphatase levels measurement and histological examination. RESULTS: MTX administration caused a significant decrease in tissue GSH, and tissue Na+, K+ ATPase activity and which was accompanied with significant increases in tissue MDA and MPO activity. Moreover the pro-inflammatory cytokines (TNF-α, IL- β) were significantly increased in the MTX group. On the other hand, ALA treatment reversed all these biochemical indices as well as histopathological alterations induced by MTX. CONCLUSION: Alfa lipoic acid ameliorates methotrexate induced oxidative damage of liver in rats with its anti-inflammatory and antioxidant effects. .

Irisin: a potentially candidate marker for myocardial infarction.

Myocardial infarction (MI) causes energy depletion through imbalance between coronary blood supply and myocardial demand. Irisin produced by the heart reduces ATP production by increasing heat generation. Energy depletion affects irisin concentration in circulation and cardiac tissues, suggesting an association with MI. We examined: (1) irisin expression immunohistochemically in rat heart, skeletal muscle, kidney and liver in isoproterenol (ISO)-induced MI, and (2) serum irisin concentration by ELISA. Rats were randomly allocated into 6 groups (n=6), (i) control, (ii) ISO (1h), (iii) ISO (2h), (iv) ISO (4h), (v) ISO (6h), and (vi) ISO (24h), 200mg ISO in each case. Rats were decapitated and the blood and tissues collected for irisin analysis. Blood was centrifuged at 1792 g for 5 min. Tissues were washed with saline and fixed in 10% formalin for histology. Serum irisin levels gradually decreased from 1h to 24h in MI rats compared with controls, the minimum being at 2h, increasing again after 6h. Cardiac muscle cells, glomerular, peritubular renal cortical interstitial cells, hepatocytes and liver sinusoidal cells and perimysium, endomysium and nucleoi of skeletal muscle were irisin positive, but its synthesis decreased 1-4h after MI. At all time-points, irisin increased near myocardial connective tissue, with production in skeletal muscle, liver and kidney recovering after 6h, although slower than controls. Unique insight into the pathogenesis of MI is shown, and the gradually decrease of serum irisin might be a diagnostic marker for MI.