Tissues Of Male Rats Research Articles

Decrease in Muscle Mass in Diet-Induced Visceral Obesity in Male Wistar Rats: Relationship with Hormonal and Metabolic Parameters

Decrease in muscle mass, as a rule, develops with the aging of the body, but in obesity the signs of decrease in mass and functional activity of the skeletal muscles are also registered, which requires experimental research. The aim of the work was to study the effect of diet-induced obesity and health variants of its correction on mass-metric and metabolic tissue parameters of musculus triceps surae in male Wistar rats. The experiments were carried out on sexually mature male Wistar rats and included the study of mass-metric, metabolic and hormonal indices characterizing the state of muscle tissue under the standard (Std, 16 weeks) and high-caloric diet (HCD, 16 weeks), during the transition from HCD to standard diet (HCD/StD, 8/8 weeks), when physical activity in the form of running on a treadmill was added (StD + running, HCD + running and HCD/StD + running, 8/8). Prolonged high-caloric diet led to the development of visceral obesity and decreased musculus triceps surae mass in male Wistar rats. Metabolic shifts were registered in the skeletal muscles during HCD, such as an increase in glucose, lactate, lactate dehydrogenase activity, and lipid peroxidation. Visceral obesity was accompanied by a decrease in serum testosterone content, but the concentration of the hormone in muscle tissue remained relatively stable. Application of moderate physical activity in HCD did not lead to correction of visceral fat mass, did not prevent decrease in muscle mass, but caused normalization of biochemical indices in muscle tissue and serum testosterone level. The most adequate correction of visceral obesity, muscle mass and biochemical indices in muscle tissue in male rats was achieved by switching from a high-caloric to a balanced diet regardless of physical activity. Thus, correction of diet-induced visceral obesity, muscle mass and associated metabolic shifts in male Wistar rats requires a transition to a balanced diet.

Effect of Aerobic Training and Melatonin Consumption on TNF-α Expression in the Spinal Cord Tissue of Male Rats with Type 1 Diabetes

Background: Neuroinflammation plays a central role in the onset and development of diabetic neuropathic pain. Objectives: This study aims to thoroughly investigate the effects of aerobic training and melatonin on TNF-α expression in rats suffering from diabetic neuropathic pain. Methods: Twenty-five male Wistar rats, aged 8 weeks and weighing 204 ± 11.3 g, were randomly assigned to one of five groups: Diabetic, melatonin-treated diabetic, exercise-trained diabetic, melatonin and exercise-trained diabetic, and control. Diabetes was induced by injecting streptozotocin (STZ) at a dose of 50 mg/kg. After verifying the development of diabetes through a pain perception test, the training group underwent six weeks of continuous aerobic training on a treadmill with an average intensity of 15 meters per minute for 30 minutes. The melatonin groups received a daily dose of 10 mg per kilogram of body weight for 6 weeks. TNF-α expression levels were measured using real-time PCR. Results: The combination of aerobic training and melatonin supplementation significantly decreased TNF-α expression levels (P < 0.05). Additionally, the levels of TNF-α expression were found to be lower in the diabetic group compared to the control group (P < 0.05). Conclusions: It appears that combining aerobic training with melatonin supplementation can regulate TNF-α expression levels and enhance the sensitivity of nociceptors to nociceptive factors resulting from the gradual deterioration of sensory neurons caused by diabetes.

Effect of Eight Weeks of Endurance Training on the Protein Levels of Some Angiogenesis Indicators in the Cardiac Tissue of Rats with Morphine Withdrawal Syndrome

Background: Exercise is a therapeutic procedure for addicts; however, its physiological mechanisms are not well understood. This study aimed to investigate the effect of eight weeks of endurance training on the levels of vascular endothelial growth factor and endostatin in the heart tissue of male rats with morphine withdrawal syndrome. Materials and Methods: This experimental study was conducted on 32 male rats randomly divided into four groups of eight: healthy control (HC), endurance training (ET), morphine control (CM), and morphine+endurance training (M.ET). Two morphine withdrawal groups were addicted to 0.4 mg/ml morphine sulfate for 21 days. The exercise groups performed eight weeks of treadmill running. At the end of the study, all rats were killed, and their heart tissue was removed. Protein levels of the indicators in this study were measured by ELISA kits. The data were analyzed by Tukey’s one-way ANOVA test. Results: The results of this study showed a significant decrease in VEGF levels (P<0.001) and a significant increase in ES (P<0.001) in the MC, compared to the HC. In addition, the increase in VEGF levels (P=0.014) and the decrease in ES (P=0.026) in the M.ET showed a significant difference, compared to the MC. Conclusion: Endurance training may be useful in preventing negative changes in angiogenesis and metabolic parameters related to morphine, which should be considered in the rehabilitation of addicts.

LONG-TERM LIGHT DEPRIVATION AFFECTS DIGESTIVE FUNCTION IN RATS DURING ONTOGENY

The effects of light deprivation on age-related changes in body weight, food and water intake, as well as the activity of digestive enzymes in pancreatic tissues of male rats was studied. Animals were divided into three groups: the first was in standard light conditions (12 h light/12 h dark, control, LD), the second was kept under conditions of long-term light deprivation from the moment of birth (LD/DD), and the third – from the prenatal period (DD/DD). Prolonged keeping of rats under conditions of light deprivation led to disruption of the age-associated dynamics of the studied parameters, at the same time, the detected changes in response to a specific light condition differed depending on the stage of ontogenesis at which its exposure began. Thus, body mass (age 3 and 18 months) and food and water intake (12 months), amylase and lipase activities (18 months) were lower, and protease activities after the end of the stable growth stage (12, 18 and 24 months) were higher in LD/DD-rats than in LD-rats. Significant changes in the studied parameters were observed under DD/DD conditions in 12‑month-old and 18-month-old rats – body mass was the largest, and food and water intake were the lowest compared to LD and LD/DD. In addition, the maximum amylase activity (1 and 6 months) among the studied groups and the higher values of total proteolytic activity during the period of stable growth (6 and 12 months) were found in DD/DD-rats compared to controls. Thus, our results indicate that light deprivation disrupts the ontogenetic development program of the digestive system of mammals.

Immunohistochemical, pharmacovigilance, and omics analyses reveal the involvement of ATP-sensitive K+ channel subunits in cancers: role in drug-disease interactions.

Background: ATP-sensitive-K+ channels (KATP) are involved in diseases, but their role in cancer is poorly described. Pituitary macroadenoma has been observed in Cantu' syndrome (C.S.), which is associated with the gain-of-function mutations of the ABCC9 and KCNJ8 genes. We tested the role of the ABCC8/Sur1, ABCC9/Sur2A/B, KCNJ11/Kir6.2, and KCNJ8/Kir6.1 genes experimentally in a minoxidil-induced renal tumor in male rats and in the female canine breast cancer, a spontaneous animal model of disease, and in the pharmacovigilance and omics databases. Methods: We performed biopsies from renal tissues of male rats (N = 5) following a sub-chronic high dosing topical administration of minoxidil (0.777-77.7mg/kg/day) and from breast tissues of female dogs for diagnosis (N = 23) that were analyzed by immunohistochemistry. Pharmacovigilance and omics data were extracted from EudraVigilance and omics databases, respectively. Results: An elevated immunohistochemical reactivity to Sur2A-mAb was detected in the cytosol of the Ki67+/G3 cells other than in the surface membrane in the minoxidil-induced renal tumor and the breast tumor samples. KCNJ11, KCNJ8, and ABCC9 genes are upregulated in cancers but ABCC8 is downregulated. The Kir6.2-Sur2A/B-channel opener minoxidil showed 23 case reports of breast cancer and one case of ovarian cancer in line with omics data reporting, respectively, and the negative and positive prognostic roles of the ABCC9 gene in these cancers. Sulfonylureas and glinides blocking the pancreatic Kir6.2-Sur1 subunits showed a higher risk for pancreatic cancer in line with the positive prognostic role of the ABCC8 gene but low risks for common cancers. Glibenclamide, repaglinide, and glimepiride show a lower cancer risk within the KATP channel blockers. The Kir6.2-Sur1 opener diazoxide shows no cancer reactions. Conclusion: An elevated expression of the Sur2A subunit was found in proliferating cells in two animal models of cancer. Immunohistochemistry/omics/pharmacovigilance data reveal the role of the Kir6.1/2-Sur2A/B subunits as a drug target in breast/renal cancers and in C.S.

(-)-Epicatechin increases apelin/APLNR expression and modifies proteins involved in lipid metabolism of offspring descendants of maternal obesity

Several studies have shown the beneficial effects of (-)-epicatechin (Epi) in metabolic profile and that this flavanol is a biased ligand of the apelin receptor. The apelinergic system is expressed in adipocytes and has been related to obesity and metabolic disorders. The study aim was to evaluate the effect of Epi on apelin, on its receptor and on proteins involved in lipolysis, lipogenesis, and adipogenesis in the retroperitoneal adipose tissue of male rats descended from obese mothers. We evaluated the effect of Epi in the retroperitoneal adipose tissue of four groups of male offspring, analyzing mRNA expression and protein levels of apelin and its Apj receptor. We also analyzed, by Western Blot, the levels of AMPKα, ACC, C/EBPα, ATGL, Fas, and FABP4 of the AP2 proteins. Epi significantly elevated apelin mRNA expression and protein levels as well as its Apj receptor. Besides, the flavanol significantly promoted AMPKα phosphorylation with the concomitant reduction of Fas, and the increase of the ATGL protein. In contrast, there was an increase in the inactive phosphorylated form of ACC and a decrease in the phosphorylated active form of C/EBPα. Similarly, Epi treatment induced a reduction in the fatty acid-binding protein 4 in the C+Epi and MO+Epi groups.In conclusion, Epi increases the expression of the apelinergic system and the active phosphorylated form of AMPKα; likewise, it modifies the expression level or active form of proteins involved in lipolysis, lipogenesis and adipogenesis in the retroperitoneal adipose tissue of male offspring of obese mothers.

The effect of eight weeks of aerobic exercise and coriander seed extract on oxidative stress and cellular energy indices of heart tissue in male rats poisoned with hydrogen peroxide

The effect of eight weeks of aerobic exercise and coriander seed extract on oxidative stress and cellular energy indices of heart tissue in male rats poisoned with hydrogen peroxide

Effect of the Anticancer Drug Doxorubicin (Adriamycin) on Antioxidant Studies and Ultrastructural Investigation in the Liver, Kidney, and Heart Tissues of Male Rats

Doxorubicin is a well-known antineoplastic agent that has proved to be successful in the treatment of various types of cancer. I used rats as the model to evaluate the effect of doxorubicin on antioxidant studies and ultrastructural investigations in the liver, kidney, and heart tissues. Male albino rats were given 1.0 mg/kg body weight of the anticancer drug doxorubicin intraperitoneally three times a week for 52 days. This was for a total of 18 doses. Control animals received 52 doses of 0.5 ml of saline over 52 days. The body weights of rats injected with doxorubicin experienced a significant decrease after the last dose compared to the control group of rats. In this study, the weights of the heart, kidneys, and liver were measured. Except for cardiac tissues, the protein content in the aforementioned tissues in treated rats was significantly different from the control. Glutathione (GSH) levels in the kidneys of experimental rats were not significantly lower (7.946 ± 0.781) compared to controls (8.06 ± 0.74) but there was a non-significant increase in GSH levels in the liver (17.095 ± 1.066) compared to controls (13.8 ± 1.3). In addition, the mean GSH levels in doxorubicin-treated hearts were significantly lower (7.9462 ± 0.781) compared to controls (8.06 ± 0.74). Lipid peroxidation (Lpx) and malondialdehyde content (MDA), a marker of lipid peroxidation, were found in much lower concentrations in the liver organ of the doxorubicin-treated group (0.0162 ± 0.00086) as compared to (0.20 ± 0.02) controls, and MDA content in the kidney was decreased (0.0239 ± 0.0003) compared to control rats (0.31 ± 0.03), as well as heat production (0.0398 ± 0.00097) compared to (47.451 ± 1.708) controls. Glutathione reductase (GR) levels were significantly elevated in the same tissue treatment group. Glutathione-S-Transferase (G-S-T) activity was assessed and significantly increased in all tissues in the doxorubicin model. Glutathione peroxidase (GPx) activity showed a significant decrease in all the above tissues after doxorubicin injection. The catalase (CAT) activity of doxorubicin was greatly increased in one treated rat. In the doxorubicin-treated group, levels of cytochrome p450 (CYTp450) were significantly decreased in liver and kidney tissue and significantly elevated in heart tissue. After doxorubicin treatment, cytochrome b5 (CYTb5) levels in liver tissues increased significantly (837.177± 61.197) compared to controls (615 ± 37.0), and the contents of cytochrome b5 in rats' kidneys increased significantly (447.685 ± 35.215) compared to controls (2605.5± 259.2). and cytochrome b5 in heart tissues was lower (165.352± 8.7) when compared to controls (88± 0.4). The results showed that there were few obvious changes in histological, ultrastructural, and biochemical changes in liver tissue in the doxorubicin model. Long-term doxorubicin treatment in kidney tissue results in no significant changes at the light microscopic level, but the electron microscopic level reveals no change from a histological point of view.

The Role of Cullin 3 in Cerebral Ischemia–Reperfusion Injury

Cullin 3 (CUL3), a member of Cullin-RING ubiquitin ligase family, regulates multiple intracellular pathways. CUL3 expression in peripheral immune cells is highly associated with the development of stroke, while little is known about the mechanism of how CUL3 participates in cerebral ischemia/reperfusion (I/R) injury. In this study, we showed that CUL3 was obviously upregulated in brain tissues of male rats received middle cerebral artery occlusion (MCAO) and reperfusion and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neurons. We firstly confirmed that CUL3 interacted with WNK3, a protein that has been proved to be associated with brain damage after ischemic stroke. CUL3 knockdown inhibited the ubiquitination of WNK3 and accelerated the phosphorylation of OSR1 in OGD/R-stimulated neurons. CUL3 silencing did not further aggravate cerebral I/R injury and played a neuroprotective role in vitro and in vivo. CUL3 knockdown attenuated the impairment of cell viability caused by OGD/R. CUL3 silencing reduced TUNEL-positive cells, down-regulated pro-apoptotic factor (Bax and Cleaved caspase 3) levels and increased the anti-apoptotic factor (Bcl-2) level in vitro and in vivo, suggesting that CUL3 repression alleviated neuronal apoptosis. Interestingly, rescue experiments revealed that WNK3 downregulation did not block the neuroprotection of CUL3 inhibition. These findings suggested that CUL3-mediated cerebral I/R injury might be not achieved through WNK3 signaling but other pathways. Furthermore, CUL3 inhibition suppressed ubiquitin-mediated degradation of Nrf2 and activated Nrf2 signaling by increasing the nuclear translocation of Nrf2 and expression levels of HO-1 and NQO-1. Taken together, CUL3 exacerbates cerebral I/R injury potentially due to its negative regulation of Nrf2 activation.

Intra-gastrically administration of Stevia and particularly Nano-Stevia reversed the hyperglycemia, anxiety, and memory impairment in streptozotocin-induced diabetic rats

Type II diabetes mellitus is a group of metabolic disorders considered chronic hyperglycemia resulting from deficits in insulin secretion or insulin function. This disease usually links with various psychological problems such as anxiety and cognitive dysfunctions. Stevia (Stevia rebaudiana Bertoni) is a natural and healthy substitute sweetener for sugar and artificial sweeteners. It has become essential for human diets and food manufacturers. The aim of this research was to investigate the effects of Stevia and Nano-stevia on the regulation of anxiety and memory processes in male diabetic rats. The elevated plus-maze (EPM) test-retest procedure was used to assess anxiety and memory in male diabetic rats. The findings exhibited that induction of diabetes caused a distorted cellular arrangement in the liver tissue of male rats. On the other hand, intra-gastrically administration of Stevia (1 ml/kg) and nano-Stevia (1 ml/kg) indicated a normal appearance in the liver tissue of male diabetic rats. Moreover, induction of diabetes caused the augmentation of blood glucose, reduction in time spent in%open-arm time (%OAT) on the test day, and enhancement of%OAT on the retest day. Therefore, induction of diabetes in rats produced hyperglycemia, anxiogenic effect, and memory impairment and these responses were reversed by drug treatment. Furthermore, intra-gastrically application of Stevia (1 ml/kg) and nano-Stevia (1 ml/kg) reversed the hyperglycemia, anxiogenic effect, and memory impairment in male diabetic rats. Interestingly, Nano-Stevia exhibited the highest significant response rather than Stevia. In conclusion, the results of this research suggested the beneficial properties of Stevia and particularly Nano-Stevia on inducing anti-diabetic effects, anxiolytic behavior, as well as memory improvement in male diabetic rats.

Zinc Improves Semen Parameters in High-Fat Diet-Induced Male Rats by Regulating the Expression of LncRNA in Testis Tissue.

This study aimed to identify differentially expressed LncRNAs in testis tissue of male rats induced by high-fat diet and their changes after zinc supplementation, by constructing a high-fat feeding rat model, and then supplemented with zinc, and observed the expression of LncRNA in three groups of normal, high-fat fed, and zinc-intervened rats. Experimental studies show that the semen parameters of male rats with high-fat diet were decreased but recovered after zinc supplementation, and the related LncRNA also changed. Zinc may improve the high-fat diet-induced reduction of semen parameters by changing the expression of related LncRNA.

Biochemical and histopathological studies of sulfonylurea derivative as a new chemotherapeutic agent against liver cancer in free- and nano-coated forms

The most frequent type of primary liver cancer is hepatocellular carcinoma (HCC), accounting for approximately 90% of primary liver cancers and a third leading cause of cancer deaths. In the current study, the synthesized compound 3 was re-formulated using tetraethyl orthosilicate (TEOS) with weight ratio (1:1) via sol-gel technique. The prepared material has been examined using Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray elemental analysis (EDX), and scanning and transmission electron microscopes (SEM and TEM). Herein, we investigate the mode of action of 3 as potent anti-liver cancer in vivo as normal and nano-forms. Rats were given a single dosage of 50 mg/kg b.wt. of HCC through an intraperitoneal injection (ip). A single dosage of CCl4 (2 ml/kg IP) was also given to rats 2 weeks later. Several liver, tumor and oxidative stress biomarkers were detected including liver enzymes; alanine and aspartate aminotransferases (ALT and AST), alkaline phosphatse (ALP), gamma glutamyl transferase (GGT), glutathione (GSH), lipid peroxide (MDA), catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), α-fetoprotein and α-L-Fucosidase. Hepatic pathological pictures were also performed for the documentation of the presence of HCC and supported the biochemical results. Moreover, the DNA damage in liver tissues of male rats using comet assay was studied. The results showed that the HePG2 (− ve) group of rats exhibited a significant reduction (P < 0.05) in DNA damage values (9.30 ± 0.89) relative to other treatment groups. Nevertheless, the DNA damage values in the HePG2 (+ ve) and 5-flurouracil groups were significantly higher (P < 0.01) compared to the HePG2 (− ve) group. Additionally, HePG2 (coated 3) and HePG2 (3) groups exhibited significant decrease in the DNA damage compared to those in HePG2 (+ ve) group.

Effect of a Mixture of Native Iranian Probiotics on Biochemical Factors and Kidney Tissue of Male Rats Exposed to Cadmium Chloride

Introduction: Cadmium (Cd) is an environmental pollutant and chemical agent that destroys cell structure in various tissues. Probiotics are normal flora bacteria that if consumed adequately, will have health benefits in addition to nutritional benefits. The aim of this study was to investigate the effect of a mixture of native Iranian probiotics on biochemical factors and kidney tissue of male rats exposed to cadmium chloride.&#x0D; Methods: In this experimental study, 21 male Wistar rats were divided into 3 groups of 7: control, cadmium chloride recipient (3mg/kg) and cadmium chloride recipient (3mg /kg) + mixture of probiotics (CFU/mL109) were divided. Single-dose cadmium chloride was given to rats by intraperitoneal injection and probiotics by gavage for 30 days. At the end of the test, blood samples were taken directly from the heart to study serum creatinine and urea concentrations by autoanalyzer method and kidney tissue was used for microscopic studies of E&amp;H staining. The data were evaluated using SPSS software version 16 and one-way ANOVA and Tukey test.&#x0D; Results: The results of Cadmium chloride significantly increased serum creatinine and urea concentrations compared to the control group (P&lt;0.05) while in the group receiving probiotic mixture compared to the cadmium chloride group showed a significant decrease. Damage to kidney tissue was also shown compared to the control group. On the other hand, the structure of kidney tissue in the group treated with a mixture of probiotics compared to the group of cadmium chloride showed improvement.&#x0D; Conclusion: It is possible to use as a candidate a mixture of native Iranian probiotics (Lactobacillus rhamnosus, Lactobacillus casei and Lactobacillus holoticus) against cadmium chloride damage to the tissues of male rats.

The Interactive Effect of Interval Training Intensity and Curcumin Supplementation on Mitochondrial Bnip3 and Parkin Gene Expression in the Heart Tissue of Male Rats' Model of Heart Infarction

The Interactive Effect of Interval Training Intensity and Curcumin Supplementation on Mitochondrial Bnip3 and Parkin Gene Expression in the Heart Tissue of Male Rats' Model of Heart Infarction

Short-Term Effect of Aerobic Exercise and High-Fat Diet and Consumption of Curcumin Extract on Leptin Gene Expression in Liver Tissue in Male Rats

Short-Term Effect of Aerobic Exercise and High-Fat Diet and Consumption of Curcumin Extract on Leptin Gene Expression in Liver Tissue in Male Rats

Increased nociceptive sensitivity is associated with periodontal inflammation and expression of chronic pain genes in gingival tissues of male rats

ObjectiveThis study aimed to evaluate the inflammatory response, hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2), and voltage-gated potassium (Kv) 9.1 channel expression in rats with paclitaxel-induced neuropathic pain-like behavior. MethodsSixteen male Sprague Dawley rats were divided equally into two groups: control and paclitaxel-induced pain (PTX). The attachment loss and inflammatory cell infiltrate levels were analyzed histometrically and immunohistochemically. The gene expression of HCN2 and KCNS1 was analyzed by qPCR in the brain and gingival tissues. ResultsThe attachment loss and prominent infiltration of inflammatory cells were significantly higher in the PTX group than in the control groups. In gingival tissues; the expression levels of HCN2 (p = 0,0011) were significantly higher and KCNS1 (p = 0,0003) were significantly lower in the PTX group than in the control groups. ConclusionIncreased nociceptive sensitivity, may play a role in periodontal inflammation. KCNS1 may decrease and HCN2 expression may increase in periodontium in permanent chronic pain states. The results of the present study may be helpful in developing new approaches to alleviate pain and maintain periodontal health in patients suffering from orofacial pain.

Fadogia agrestis (Schweinf. Ex Hiern) Stem Extract Restores Selected Biomolecules of Erectile Dysfunction in the Testicular and Penile Tissues of Paroxetine-Treated Wistar Rats.

Inadequate release of nitric oxide (NO) by the penile tissue impacts negatively on penile erection causing erectile dysfunction (ED). Fadogia agrestis has been implicated in the management of ED without information on key biomolecules associated with ED in male rats. Therefore, this study evaluated the influence of aqueous extract of Fadogia agrestis stem (AEFAS) on key biomolecules associated with ED in the penile and testicular tissues of male Wistar rats induced with ED by paroxetine. Thirty male rats were assigned into 6 groups (I, II, III, IV, V and VI) of 5. Group I (sham control, without ED) was administered distilled water orally. Paroxetine-induced ED rats in groups II (negative control), III (positive control), IV, V and VI received distilled water, sildenafil citrate (SC, 50mg/kg body weight) and AEFAS at 18, 50 and 100mg/kg body weight respectively. Paroxetine lowered/reduced (p < 0.05) the MF, IF, EF, NO, cGMP, catalase, SOD, T-SH, GSH and GST whilst it prolonged/increased ML, IL, EL, PEI, AChE, PDE5, arginase, ACE, TBARS and H2O2. Contrastingly, AEFAS like sildenafil citrate increased (p < 0.05) the penile and testicular NO, cGMP, catalase, SOD, T-SH, GSH and GST and reduced AChE, PDE5, arginase, ACE, TBARS and H2O2 to levels that compared favourably (p > 0.05) with those of sham control. The study concluded that AEFAS restored the NO/cGMP pathway and ED-associated key enzymes in the penile and testicular tissues of male rats via antioxidant means. The study recommended the use of aqueous extract of Fadogia agrestis stem in managing ED after clinical trials.

Simultaneous Quantification of Steroid Hormones Using hrLC-MS in Endocrine Tissues of Male Rats and Human Samples.

Steroid hormones play a vital role in the regulation of cellular processes, and dysregulation of these metabolites can provoke or aggravate pathological issues, such as autoimmune diseases and cancer. Regulation of steroid hormones involves different organs and biological compartments. Therefore, it is important to accurately determine their levels in tissues and biofluids to monitor changes after challenge or during disease. In this work, we have developed and optimized the extraction and quantification of 11 key members of the different steroid classes, including androgens, estrogens, progestogens and corticoids. The assay consists of a liquid/liquid extraction step and subsequent quantification by high-resolution liquid chromatography coupled time-of-flight mass spectrometry. The recoveries range between 74.2 to 126.9% and 54.9 to 110.7%, using a cell culture or urine as matrix, respectively. In general, the signal intensity loss due to matrix effect is no more than 30%. The method has been tested in relevant steroidogenic tissues in rat models and it has also been tested in human urine samples. Overall, this assay measures 11 analytes simultaneously in 6 min runtime and it has been applied in adrenal gland, testis, prostate, brain and serum from rats, and urine and extracellular vesicles from humans.

A resveratrol derivative modulates TRH and TRH-like peptide expression throughout the brain and peripheral tissues of male rats.

IntroductionResveratrol and related polyphenols have therapeutic effects ranging from treatment of depression, Alzheimer's and Parkinson's disease, obesity, diabetes, neurodegeneration and ageing. TRH and TRH‐like peptides, with the structure pGlu‐X‐Pro‐NH2, where ‘X can be any amino acid reside, have reproductive, caloric‐restriction‐like, anti‐ageing, pancreatic‐β cell‐enhancing, cardiovascular and neuroprotective effects. We hypothesize that TRH and TRH‐like peptides are mediators of the therapeutic actions of the resveratrol derivative pterostilbene (PT).MethodsSixteen young adult male Sprague–Dawley rats were divided into four groups. Control group remained on ad libitum chow and water for 10 days. Acute group received ad libitum chow and water for 9 days and then 0.9 g PT/250 g rat chow for 24 h. Chronic animals received PT in chow for 10 days. Withdrawal rats received PT chow for 8 days and then normal chow for 2 days. TRH and TRH‐like peptide levels were measured in medulla oblongata (MED), frontal cortex (FCX), hypothalamus (HY), amygdala (AY), hippocampus (HC), piriform cortex (PIR), nucleus accumbens (NA), entorhinal cortex (ENT), striatum (STR), cerebellum (CBL), anterior cingulate (ACNG), posterior cingulate (PCNG), prostate (PR), liver (L), testis (T), heart (H), pancreas (PAN), adrenals (AD) and epididymis (EP).ResultsSignificant changes in the levels of TRH and TRH‐like peptides occurred throughout the brain and peripheral tissues in response to PT treatment.ConclusionThe high responsiveness of PIR, CBL, HY, STR, PCNG, MED, FCX, NA, ACNG and AY in brain and EP and PR is consistent with TRH and TRH‐like peptides participating in the therapeutic effects of PT.

ИЗУЧЕНИЕ НЕКРОТИЗИРУЮЩЕГО ДЕЙСТВИЯ 0,2 % РАСТВОРА НОРАДРЕНАЛИНА ГИДРОТАРТРАТА НА ТКАНЬ ПРОСТАТЫ КРЫС ПРИ ИНЪЕКЦИОННОМ ВВЕДЕНИИ ЕГО В ПРОСТАТУ

Abstract. Background. Previously, we first formulated the concept of targeted prostatic pharmaconecrosis (TPPhN). TPPhN is the death of those areas of the prostate tissue, that are proven or suspected to contain tumor cells of prostate cancer, due to the direct injection of a pharmacologically active substance into the prostate tissue. The aim: to study whether TPPhN occurs in the prostate tissue of male rats three hours after injection of 0.05 ml noradrenaline hydrotartrate (NH) solution into it. Materials and methods. The experiments were carried out on 12 outbred male rats aged 10 months. The animals were divided into two groups of six individuals each. Under anesthesia, the rats of the first group received only the injection of 0.05 ml 0,2% solution of NH into the left lobe of the prostate. Rats of the second group first received doxazosin 0.00025 g intragastrically, and then an intraprostatic injection of 0.05 ml of a 0.2 % solution of NH into the left lobe of the prostate was made. 3 hours after intraprostatic injection, macroscopic changes in the left lobe of the prostate were assessed, then the left lobe was resected. Results and conclusions. In all experiments, a demarcation line was clearly visible, delimiting the focus of TPPhN from intact tissue of the prostate. Typical morphological changes in the prostate tissue in the focus of TPPhN were studied. Close attention was paid to the characteristics of the ischemic penumbra between the focus of TPPhN and intact prostate tissue. It was found that in animals of the second group, the penumbra turned out to be clearer and narrower; due to this, the focus of TPPhN was sufficiently sharply delimited from normal prostate tissue. The fact established by us allows us to consider such a combination of substances as promising in the development of the TPPhN technique in humans.