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.

Effects of Carnosine, Ankaferd, and Silver Sulfadiazine on an Experimental Burn Model: Roles of Irisin and HSP70.

In this study, the effects of carnosine, ankaferd, and 1% silver sulfadiazine applied topically on second-degree burns were investigated and the roles of irisin and Heat shock protein 70 (HSP70) in this healing process were evaluated. Ninety male albino rats were used and divided into five groups. The groups were classified as control, burn, burn + carnosine (CAR), burn + ankaferd (ABS), and burn + silver sulfadiazine (SS). It was found that level of irisin increased in the first week and decreased in the second week in the burn and CAR groups. In the ABS and SS groups, the level of irisin was determined that started to increase in the first week and continued to increase in the second week. The level of HSP70 was found to increased in the first week in burn and CAR groups and decreased in the second week, but started to increase in the second week in ABS and SS groups. Both levels of irisin and HSP70 were observed to decreased in all treatment groups in the third week. In this study, it was shown that ankaferd and silver sülfadiazine treatments cause an increase in the irisin levels in the early period and a gradually increase in HSP70 levels in the later period in burns. The inflammatory response was observed to be limited in the early period in the ankaferd and sulfadiazin groups. It was concluded that these findings were effective in early wound healing in burns.

The combined effect of pomegranate extract and tangeretin on the DMBA-induced breast cancer model.

The aim of this study was to investigate the protective effects of pomegranate extract and tangeretin alone or in combination in DMBA-induced rat breast cancer model. A total of 68 female rats were randomly divided into 8 groups. The first 4 groups were designed as controls for cancer and treatment groups, and the control groups were composed of only control (C), Pomegranate (P), Tangeretin (T), and Pomegranate+Tangeretin (P+T) groups. The other four groups were designed as cancer and treatment groups and were composed of DMBA (D) and DMBA+Pomegranate (D+P), DMBA+Tangeretin (D+T), DMBA+Pomegranate+Tangeretin (D+P+T) groups. Tumor markers and angiogenesis parameters were studied from plasma samples obtained from rats. Histopathological, immunohistochemical, and TUNEL analyses and expressions of proteins affecting apoptosis and cell cycle were determined in breast tissue samples. In the DMBA group, plasma CA15-3, CEA, VEGF, MMP-9, and NF-κB levels were significantly increased compared to the controls, but significant decreases were observed in these parameters except MMP-9 in the treatment groups. It was observed that p53 and Bax expressions significantly increased in both D+P and D+P+T groups compared to the DMBA group, and these findings were supported by Tunel and immunohistochemical findings. Cyclin D1 expressions were found to be significantly decreased only in the D+T group and supported by TUNEL and immunohistochemical findings. Immunohistochemical ER-α and Ki-67 immune reactivities were significantly decreased in all treatment groups compared to the DMBA group. Our results showed that combined application of pomegranate extract and tangeretin may be more beneficial in preventing breast cancer development.

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 carnosine supplementation on apoptosis and irisin, total oxidant and antioxidants levels in the serum, liver and lung tissues in rats exposed to formaldehyde inhalation.

The main objective of the study has been to show whether carnosine has positive effects on liver and lung tissues of rats exposed to a range of formaldehyde concentrations, and to explore how irisin expression and antioxidant capacity are altered in these tissues by carnosine supplementation. Sprague-Dawley type male rats were divided into 8 groups with 6 animals in each: (I) Control; no chemical supplementation); (II) sham (100mg/kg/day carnosine); (III) low dose formaldehyde (LDFA) for 5 days/week; (IV) LDFA for 5 days/week and carnosine); (V) moderate dose formaldehyde (MDFA) for 5 days/week); (VI) MDFA for 5 days/week and carnosine; (VII) high dose formaldehyde (HDFA) for 5 days/week; (VIII) and HDFA for 5 days/week and carnosine. Sham and control groups were exposed to normal air. Irisin levels of the serum, liver and lung tissue supernatants were analyzed by ELISA, while the REL method was used to determine total oxidant/antioxidant capacity. Irisin production by the tissues was detected immunohistochemically. Increasing doses of FA decreased serum/tissue irisin and total antioxidant levels relative to the controls, as also to increases in TUNEL expressions, total oxidant level, oxidant and apoptosis index. Irisin expression was detected in hepatocyte and sinusoidal cells of the liver and parenchymal cells of the lung. In conclusion, while FA exposure reduces irisin and total oxidant in the serum, liver and lung tissues in a dose-dependent manner and increases the total antioxidant capacity, carnosine supplementation reduces the oxidative stress and restores the histopathological and biochemical signs.

Copeptin, adropin and irisin concentrations in breast milk and plasma of healthy women and those with gestational diabetes mellitus.

Copeptin, adropin and irisin are polypeptide hormones implicated in energy homostasis and diabetes. The purposes of this study were (1) to compare the copeptin, adropin and irisin concentrations between colostrum, transitional and mature milk and plasma in lactating women with and without GDM and (2) to compare these values with those from non-lactating women. Venous blood samples were obtained before suckling from 15 healthy lactating women aged 26-30 years, 15 lactating women with GDM aged 26-32 years, and 14 age-matched controls aged 25-31 years. Colostrum, transitional milk and mature milk samples were collected just before suckling. The concentration of copeptin was determined by EIA while the concentrations of adropin and irisin were determined by ELISA. The levels of copeptin, adropin and irisin in the colostrum were significantly higher than those in transitional and mature milk samples from healthy women; also, transitional milk had higher copeptin, adropin and irisin concentrations than mature milk. The amounts of copeptin in the colostrum and transitional milk were significantly higher than in mature milk samples from women with GDM, while the amounts of adropin and irisin were significantly lower. The relative concentrations of copeptin, adropin and irisin in the plasma samples from these groups of women were similar to those in the colostrum, transitional and mature milk samples, but the latter concentrations were higher than those in the plasma. These peptides could influence the regulation of metabolic pathways and the postnatal growth and development of different organs in the newborn.

The apoptotic effect of a high dose of toluene on liver tissue during the acute phase: an experimental study.

The aim of this study is to investigate the acute toxic effects of high-dose toluene and its mechanisms on the liver tissue of toluene-treated rats. In this study, 16 adult male Wistar albino rats (200-220 g) were divided into two equal groups. Group I was used as a control group, while group II was exposed to high dose of toluene, 5200 mg/kg (6 ml/kg per gavage). After the 3-hour experimental period, blood samples and liver tissues were taken from the euthanized animals. Serum aspartate and alanine aminotransferase levels were assayed. Liver tissues were fixed in 10% neutral formalin, then embedded in paraffin and sectioned (5 µm thickness). Sections were stained with hematoxylin and eosin for histopathological examination. A terminal transferase dUTP nick end labeling assay was also done for the determination of apoptosis in liver tissues. For the determination of Bax and caspase-3 immunoreactivity, the sections were stained using avidin-biotin-peroxidase immunohistochemical method. The level of plasma transaminase was found to be increased in toluene administered rats. Additionally, slight degeneration of hepatocyte and mononuclear cell infiltration was observed in the liver tissue sections and a high (+++) immunoreactivity for Bax and caspase-3 protein was observed in the toluene group. This study showed that the high dose of toluene triggers apoptosis in the liver of rats via the mitochondrial pathway in acute period.

Acute cardiotoxic effects of high dose toluene: an experimental study.

OBJECTIVE: This study aimed to investigate the acute cardiotoxic effects of high dose toluene and its damage mechanisms on heart tissue in the acute period. METHODS: Twenty adult male Wistar Albino rats (200-220 g) were used in this controlled experimental animal study. Animals were divided into two equal groups: a control group (Group 1) and a high dose (6 mL/kg/gavage) toluene-administered group (Group 2). Arterial blood pressure (BP) and heart rate (HR) values were measured at 30th, 60th and 90th minutes after toluene was administered. At the end of the experimental period, blood samples and heart tissues were taken from the rats. Serum troponin T levels were assayed. Heart tissue sections were stained using routine histological methods and examined under a light microscope. In addition, the sections were immunohistochemically stained using the avidin-biotin-peroxidase method to determine caspase-3 immunoreactivity and TUNEL to detect apoptosis. To compare the apoptotic index, the Mann-Whitney U test was used. For comparisons between the two groups, the independent t- test was used. In addition, time-based changes of intra-group parameters were evaluated using paired t tests. RESULTS: BP and HR values were low in toluene-treated rats compared to the control group. Troponin T levels were increased in toluene-administered animals as compared with controls [Toluene group: 0.140 (0.010-2.000) ng/mL vs control group: 0.010 (0.010-0.010) ng/mL, p=0.01]. Histopathologic examination of heart tissue sections showed congestion and edema in toluene administrated rats. Higher TUNEL positivity and (+++) immunoreactivity for caspase-3 protein were observed in the toluene group compared to the control group. CONCLUSION: The present study demonstrated that high doses of toluene cause apoptosis and may lead to impairment of cardiac function in the acute period.

Effects of vitamin D3 (cholecalciferol) on adriamycin-induced nephrotoxicity.

Although immune-mediated pathogenesis in adriamycin (ADR)-induced nephropathy has been proposed recently, studies are lacking about the effects of immunmodulators, such as vitamin D, on ADR-induced nephrotoxicity. We hypothesized that vitamin D(3) (cholecalciferol) would be beneficial on ADR-induced nephropathy because of its immunmodulatory properties. Eighteen male Wistar rats were divided into three groups (n = 6): group 1 (control), group 2 (single ADR injection intravenously), and group 3 (similar single ADR injection intravenously + daily oral cholecalciferol for 21 days) were used in the study. A single high dose of ADR resulted in increased urinary protein: creatinine ratio for all three weeks of the experiment in both groups 2 and 3 compared with the controls. Histological examination of the kidney tissue revealed distinct tubular lesions as tubular necrosis, hyaline casts in tubular lumen, tubular degeneration, tubular dilatation, and tubular vacuolization in group 2 compared with group 1. These tubular lesions were significantly reduced in group 3 compared to group 2. The results of this study indicate that cholecalciferol causes satisfactory tubulointerstitial recovery in ADR-induced nephrotoxicity in rats.