Blood Congestion Research Articles

Role of alpha lipoic acid on cyclophosphamide induced cardiotoxicity in adult male albino rat: histological study

Background: Cyclophosphamide is a chemotherapeutic agent used for treatment of leukemia, lymphoma and myeloma. Several studies reported wide range of cyclophosphamide induced cardiotoxicity in cancerous patients. Alpha lipoic acid is a natural antioxidant used widely for prevention and treatment of different conditions. Aim of the work: This work was conducted to study the role of alpha lipoic acid in cyclophosphamide induced cardiotoxicity basing on histological and ultrastructural studies. Material and Methods: Forty-four adult male Albino rats were divided into four groups: group I (control), group II (alpha lipoic acid -treated) in a dose (25 mg/kg body weight/day) given orally, group III (cyclophosphamide -treated) in a dose (200 mg/kg body weight) single dose injected intraperitoneally and group IV (alpha lipoic acid plus cyclophosphamid-treated). The experiment was conducted for ten days. Cardiac muscle specimens were subjected to light, electron microscopic and immunohistochemical study. Results: Microscopic examination of cardiac muscle of cyclophosphamide treated group (III) showed focal disruption and vacuolation of cardiac muscle fibers with mononuclear infiltration between cardiac muscle fibers. Ultrastructurally, destruction of myofibrils, swollen, irregular arranged mitochondria and dilated SER were noted. Some nuclei showed chromatolysis and others were heterochromatic with irregular nuclear membrane. These results were confirmed by significant decrease in Bcl2. The intercellular spaces were wide contained dilated congested blood vessels and collagen. Alpha lipoic acid administration improved cardiac muscle architecture but still not attained the complete normal morphology Conclusion: Supplementation of alpha lipoic acid in concomitant with cyclophosphamide (CYP) can ameliorate the CYP induced cardiac injury.

Blood–Brain Barrier Dysfunction After Smoke Inhalation Injury, With and Without Skin Burn

Only a handful of published reports exist today that describe neurological complications following smoke inhalation injury. In this study, we characterize acute pathophysiological changes in the brain of sheep exposed to smoke inhalation, with- and without third-degree skin burn that models the injuries sustained by human victims of fire accidents. Blood-brain barrier integrity and hemorrhage were analyzed throughout the brain using specific histological stains: Hematoxylin & Eosin, Luxol fast blue, Periodic acid-Schiff (PAS), and Martius, Scarlet and Blue (MSB). Our data show that, following smoke inhalation injury, alone and in combination with third-degree skin burn, there was a significant increase in the number of congested and dilated blood vessels in the frontal cortex, basal ganglia, amygdala, hippocampus, pons, cerebellum, and pituitary gland as compared to sham-injured controls. Positive PAS staining confirmed damage to the basement membrane of congested and dilated blood vessels throughout the brain. Severe rupturing of blood vessels, microvascular hemorrhaging and bleeding throughout the brain was also observed in the injured groups. No significant changes in hemodynamics and PaO2 were observed. Our data demonstrate for the first time that acute smoke inhalation alone results in diffuse blood-brain barrier dysfunction and massive bleeding in the brain in the absence of hypoxia and changes in hemodynamics. These findings provide critical information and prompt further mechanistic and interventional studies necessary to develop effective and novel treatments aimed at alleviating CNS dysfunction in patients with smoke and burn injuries.

The possible alleviating effect of saffron on chlorpyrifos experimentally induced cardiotoxicity: Histological, immunohistochemical and biochemical study

IntroductionPesticides are responsible for many occupational health hazards among farmers in developing countries. Chlorpyrifos (CPF) is one of the broad-spectrum organophosphorus (OP) insecticides used for agricultural, domestic and industrial purposes. Aim of the workThe present study was designed to examine the effects of CPF on cardiac muscles and to evaluate the possible protective role of crocin using biochemical and histological methods with the intention to recognize the molecular tools of its probable cardioprotective effects. Materials and methodsThirty-six adult male albino rats were used in this study and were divided into 4 equal groups (9 rats each): negative control group, positive control group, CPF treated group and CPF & crocin treated group. The heart was removed for histological and immunohistochemical studies. ResultsStained sections of cardiac muscle fibers of group III with H&E revealed remarkable histological changes in the form of disorganization of the fibers with increase in the interstitial spaces between these fibers. Congested dilated blood capillaries could be observed with extravasation of the red blood cells leading to interstitial hemorrhage. Focal areas of mononuclear cellular infiltration could be seen in the interstitial tissue. A number of cardiac fibers achieved pale acidophilic vacuolated sarcoplasm while others achieved dark homogenous acidophilic sarcoplasm. Some nuclei were peripherally situated and pyknotic while others were centrally situated and encircled with halos. Apparently increased masses of collagen fibers among the cardiac muscle fibers and around the congested dilated blood vessels with the presence of focal parts of extensive collagen fiber deposition were noticed in Mallory-stained sections of group III. Strong positive immunoreactions in the endomysium and perimysium of the cardiac fibers, along with the walls of blood capillaries and in interstitial cells, could be detected in immunohistochemical staining sections of group III with vimentin antibody. Immunoreactivity to caspase 3 was higher in the sarcoplasm of the cardiac fibers of group III compared to that of control group. A highly significant decrease in the cardiac level of SOD and CAT; however, a highly significant increase in MDA level was noted between the control groups and CPF treated group.Additionally, there was a significant improvement of the chemical and histological representations of group IV, and these improvement pictures were toward the normal. ConclusionThe study concludes that crocin can alleviate the toxic effect of chlorpyrifos caused by oxidative stress on cardiac muscle.

THE IMPACT OF THE MINERAL WATER COMPOSITION ON THE POPULATION HEALTH

Studied the issues of the water quality suitable for consumption in some mountainous regions of Lviv region, in particular in Skolivsky, Turkivsky, and Starosambirsky districts. The obtained results based on the main hydrochemical indicators show the water quality meets the requirements for the degree of pollution of the hygienic classification of water objects. The conditions for the habitat of hydrobionts and terrestrial biota are normal. Most water samples have a weakly alkaline reaction, indicating a possible high content of hydrocarbonates. Concerning the hardness, all studied samples are soft and medium hard water types. The value of total alkalinity of water samples ranges from 1.8 to 6.1 mmol/m3, which corresponds to the physiological integrity of the composition of drinking water. Sulphate ions and chloride ions are present in almost all natural waters, their content is mainly due to chemical weathering with sedimentary rocks during oxidation of sulfides, dissolution of sulfur-containing and chlorine-containing minerals.It has been investigated the sequence between hardness of water and non-infectious diseases in the studied regions. Constant consumption of such water may cause a danger to the population suffering from cardiovascular disease, blood congestion, myocardial infarction.

Effect of taxifolin on development of retinopathy in alloxan-induced diabetic rats

Purpose: Diabetic retinopathy (DR) is one of the leading causes of blindness. In DR patients, antioxidant defence is disrupted, and production of reactive oxygen species and pro-inflammatory cytokines such as interleukin 1β (IL-1β) and tumour necrosis factor alpha (TNF-α) increases. Taxifolin has been reported to suppress reactive oxygen species, IL-1β and TNF-α production. The aim of this study is to biochemically and histopathologically examine the protective effect of taxifolin against DR damage induced by alloxan.Materials and methods: Alloxan received rats with a blood glucose level of ≥250 mg/dL were divided into taxifolin-treated (TAX) (n = 6), diabetic control (DC) (n = 6) groups. There were rats received only saline in non-diabetic control (NC) group (n = 6). Taxifolin (50 mg/kg) was orally administered to the TAX group rats. DC and NC rats received the same volume of saline as a solvent. This procedure was repeated once a day for 3 months. At the end of this period, animals were killed by high dose thiopental sodium anaesthesia. Histopathological examinations were then performed on excised rat eyes. Malondialdehyde (MDA), total glutathione (tGSH), IL-1β and TNF-α levels were measured in obtained blood samples.Results: MDA, IL-1β and TNF-α levels were significantly increased in blood samples of DC group rats with hyperglycemia induced by alloxan compared with NC group (p < 0.0001), and decreased in the TAX group compared with the DC group (p < 0.0001). The levels of tGSH were significantly decreased in blood samples of DC group rats compared with NC group (p < 0.0001), and increased in the TAX group compared with the DC group (p < 0.0001). Histopathologically, retinal ganglion cells of the TAX group had a slightly dilated and congested blood vessel, and severe damage was inflicted to the retinal ganglion cell layer of the DC group.Conclusions: Experimental results suggest that taxifolin may be beneficial in the treatment of DR.

Cardio-protective Effect of Vitamin E on Doxorubicin-Induced Cardiotoxicity in Adult Male Albino Rats: A Histological and Biochemical Study

Background: Doxorubicin (Dox) is a powerful and greatly effective drug in cancer. However, its clinical usefulness is still restricted due to its specific toxicity to the cardiac tissue. Vitamin E is a well-known antioxidant used as a dietary supplement.Aim of the work: To evaluate the possible protective effects of vitamin E against Dox-induced cardiotoxicity.Material and Methods: Forty 3-months adult male albino rats weighing 200-250 gm were divided into four equal groups: Group (I): served as a negative control and received no treatment. Group (II): served as a positive control and treated with an intraperitoneal injection of 0.9% sodium chloride saline once daily for one week. Group (III): treated with 4mg Dox/kg b.w./day intraperitoneally for one week. Group (IV): was pretreated with 100mg vitamin E/kg body weight/day orally for 2 weeks followed by a combination of an intraperitoneal injection of Dox and oral vitamin E for one week in the same previous doses. Then, the animals were anaesthetized and blood samples were utilized for measurement of lactate dehydrogenase (LDH), creatine kinase (CK), triglyceride, total cholesterol and high-density lipoprotein (HDL-C). Animals were sacrificed, and a portion of each heart was taken from all groups for determination of the levels of total cardiac antioxidant capacity (TAC). The remaining portions of the heart muscle were prepared for light and electron microscopic studies.Results: Administration of Dox resulted in histological alterations in the form of vacuolated disorganized cardiac muscle fibers, degenerated mitochondria and congested dilated blood vessels. Also, significant decreases of cardiac TAC and serum HDL-C and increases of serum levels of LDH, CK, triglyceride and total cholesterol of Dox-treated group were noticed in comparison with the control ones. Pre and concomitant administration of vitamin E with Dox improved these alterations.Conclusion: Vitamin E ameliorates the cardiac damage induced by Dox.

Histological, immunohistochemical and biochemical study of the effect of triclosan and its withdrawal on cauda epididymis of adult albino rat

Background: Triclosan (TCS) is a bactericide used in many daily products. TCS potential for endocrine disruption is suspected to impact male reproductive system.Aim of the study: Is to evaluate the effect of TCS and its withdrawal on the cauda epididymis of adult albino rat using different histological and biochemical techniques.Materials & Methods: Twenty-one adult male albino rats were equally divided into 3 groups; control, TCS-treated (administered 200mg/kg/day for 8weeks) and TCS-withdrawal group (administered 200mg/kg/day for 8weeks then left without treatment for 8weeks). Serum testosterone was quantified and epididymal specimens were processed for light and electron microscopic examination. Immunohistochemical staining against androgen receptor was performed.Results: TCS-treated group revealed a significant decrease in serum testosterone. Principal cells showed vacuoles compressing their nuclei, some pyknotic nuclei and sparse stereocilia. Many adluminal halo cells were observed. The epithelial lining depicted focal areas of stratification and areas of discontinuity. Widened interstitium inbetween the ducts with cellular infiltrations and some congested blood vessels were observed. Mallory-trichrome staining revealed prominent collagen fibers surrounding the epididymal ducts and blood vessels and an enhanced Periodic-Acid-Schiff reaction in the thickened basal lamina coupled to a diminished Periodic-Acid-Schiff reaction in the apical parts of the epididymal epithelial cells. A weak nuclear androgen receptor immunoreaction in the epididymal epithelial lining of the ducts was detected. Ultrastructural examination depicted principal cells with irregular nuclei, vacuolated cytoplasm with many lysosomes, dilated Golgi apparatus and rough endoplasmic reticulum. Irregular apical cytoplasmic projections and sparse stereocilia were observed. Clear cells showed some cytoplasmic projections, large apical vacuoles and few lipid droplets. Migrating halo cells with vacuolated cytoplasm were observed. Withdrawal group showed a near normal histology.Conclusion: TCS has extremely affected the epididymal lining through acting as an endocrine disruptor. Withdrawal of TCS exerted a satisfactory outcome.

Effects of cadmium chloride on some endocrine glands (thyroid and adrenal) in male rats (Rattus norvegicus)

This study was designed to evaluate the cytotoxic effects of cadmium chloride (CdCl2) on thyroid and adrenal gland of male rats (Rattus norvegicus). Thirty six male rats were used and randomly into three groups each of 12 rats, the first group(G1) kept as at control. The 2nd and 3rd groups (G2 and G3) were administrated orally cdcl2 at doses of 15 and 20 mg/kg.B.W. respectively for 6 weeks. After the treatment period, the rats were sacrificed, then thyroid and adrenal glands were removed and processed for light microscope. Light microscopic examination of thyroid gland with (15mg/kg.B.W.) showed increase in the size of follicles, some of these follicles appeared empty from any colloidal substance and heavily infiltrated by inflammatory cells, with depletion of parafollicular cells. Vaculated follicles may be clear in other sections, and showed congested blood vessels, vascularized stroma, hyperplasia of thyrocyte in rats treated with 20 mg/kg.B.w. Results also noted changes in different regions of adrenal gland related to rats exposure tocdcl2 with 15 mg/kg.B.W., these includes cellular debris, necrosis of cortical cells, amorphous material in the zona fasciculate and focal necrosis in zona granulosa with disruption of normal structure and replaced by necrotic cells and inflammatory cells, also obvious adipocytes infiltration which appeared clear in medulla. Most changes occurred within the adrenal cortex and appeared more severity than that in the medulla region. Hypereosinophilia, pyknotic nuclei, congested blood vessels, hemorrhage, degeneration and inflammation also seen in both regions (cortex and medulla) of adrenal gland from rat exposed to cdcl2 at 20 mg/kg.B.W.

Hyptis verticillata attenuates dyslipidaemia, oxidative stress and hepato-renal damage in streptozotocin-induced diabetic rats

AimsChronic hyperglycaemia in diabetes mellitus (DM) increases the production of free radicals which results in oxidative stress and related disorders such as cardiovascular diseases, compromised hepatic and renal functions. Hyptis verticillata reportedly demonstrated glucose lowering activity in previous studies. The present study therefore evaluated the effect of H. verticillata on hyperglycaemia-induced dyslipidaemia, hepatorenal distortions, oxidative stress, as well as calculated indices of cardiovascular function. MethodsWistar rats employed for this study consisted of normoglycaemic and diabetic rats in nine experimental groups. The normoglycaemic and diabetic rats were either treated with metformin (500 mg/kg b.w.), quercetin (10 mg/kg b.w.), or ethanol extract of H. verticillata leaf (250 mg/kg b.w. and 500 mg/kg b.w.) administered orally for 28 days. Key findingsResults revealed that H. verticillata significantly lowered blood glucose level, attenuated dyslipidaemia, decreased atherogenic coefficient, atherogenic and coronary risk indices, and increased cardioprotective index in diabetic rats. Also, H. verticillata significantly decreased serum urea, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and unconjugated bilirubin levels, relative to untreated diabetic rats. Further, H. verticillata increased serum superoxide dismutase, catalase and glutathione peroxidase activities and glutathione level, and decreased malondialdehyde level in diabetic rats in a manner similar to metformin and quercetin. Histopathological investigation of the liver and kidney revealed restored hepatocytes and amelioration of congested interstitial blood vessel of the Bowman's space of the kidneys upon intervention with H. verticillata. SignificanceH. verticillata in addition to its anti-hyperglycaemic activity ameliorates oxidative stress, dyslipidaemia, atherogenicity and hepatorenal lesions in DM.

Oxidative and Cellular Metabolic Stress of Fish: An Appealing Tool for Biomonitoring of Metal Contamination in the Kolkata Wetland, a Ramsar Site.

Thepresent study delineate the various biochemical and histopathological tool to evaluate as strong biomarker in the field condition for detection of the least and maximize level of pollution and contamination. We have collected Labeo rohita from 13 different sites from East Kolkata wetland to determine biochemical and histopathological status to analyse metal contamination in the significant biological hot spot EKW. The biochemical marker as antioxidative status, i.e., catalase, superoxide dismutase (SOD), and glutathione-S-transferase (GST) in liver and gill, were remarkably higher (p < 0.01) at some of the sampling sites, but catalase in brain, SOD in kidney, GST in brain and kidney, and neurotransmitter as acetylcholine esterase (AChE) in brain were not significant (p > 0.05) among the sampling sites. The glycolytic enzymes, such as lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) in liver, gill, and muscle, and protein metabolic enzymes, such as alanine amino transferase (ALT) and aspartate amino transferase (AST) in liver, gill, muscle, and kidney, were noticeably higher (p < 0.01) at some of the sampling sites. The histopathology of the liver and gill were altered at different sampling sites, such as blood congestion, leucocyte infiltration with parenchymal vacuolisation, nucleus with blood vessels, hepatocytes granular degeneration, haemorrhage, karyorrhexis, shrink nucleus, and pyknotic nuclei in liver. In the gill, structural changes, such as complete destruction and shortening of secondary gill lamellae, blood vessel in gill arch, curling of secondary gill lamellae, aneurism in gill lamellae, and neoplasia, were observed. Most of the metals were found within the safe limit all along the 13 sampling sites, indicating that fishes are safe for the consumption. Based on our finding, we could recommend that a rational application of biochemical profiles, such as oxidative and metabolic stress parameters, including histopathology to be used as biomarkers for biomonitoring the metal contamination in the aquatic environment.

Renal Cortical Structural Alterations in Atorvastatin-treated Rats and the Possible Protective Mechanisms of L-Carnitine

The present study investigated the structural changes in rat kidney following administration of atorvastatin and evaluated the possible protective role of L-carnitine. Rats were divided into four groups, group I- control group, group II received L-carnitine at 100 mg/kg/d, group III received atorvastatin at 80 mg/kg/d and group IV received atorvastatin plus L-carnitine. Hematoxylin and Eosin, periodic acid-Schiff, inducible nitric oxide synthase, proliferating cell nuclear antigen expression and electron microscopy investigation were performed. Light microscopy results of atorvastatin group showed severe atrophic glomeruli with widened glomerular spaces. Some renal tubules showed cytoplasmic vacuolations, loss of brush borders, hemorrhage and mild congested blood capillaries. Strong positive inducible nitric oxide synthase and proliferating cell nuclear antigen immunostaining in the tubules were observed. Ultrastructurally, the proximal convoluted tubules had small electron dense nuclei, numerous lysosomes, partial loss of microvilli and vacuolations. The podocytes revealed united foot processes and increase in the thickness of the glomerular basement membrane. L-carnitine preserved the structure of renal cortex, decreased inducible nitric oxide synthase and increased proliferating cell nuclear antigen reaction. In conclusion, atorvastatin exerted a deleterious effect and L-carnitine improved most of the histological changes produced by atorvastatin.

Does hypersensitive teeth show pulp inflammation?

ABSTRACT Objective: This study investigated the presence of inflammatory response in the dental pulp of rats showing hypersensitive dentin, induced by erosive episodes. Methods: Sixteen Wistar rats were fed with commercial sucrose-free pellet diet for 12 hours; whereas the food was removed during the remainder of the day, and the animals received mineral water or a lemon-based sucrose-free soft drink, according to the group to which they belonged. Eight animals consumed the soft drink to induce hypersensitivity, while the other 8 animals received mineral water (control). After six weeks, the animals were euthanized, the mandible was removed and subjected to a median incision in the sagittal plane, to obtain right and left hemimandibles. The slides stained with hematoxylin-eosin were analyzed using light microscopy. Results: Histological evaluation of the control and experimental groups revealed no inflammatory process in the pulp tissue, and the presence of inflammatory cells, such as lymphocytes, plasma cells, eosinophils and macrophages, was not observed. In addition, there was no edema or dilated and congested blood vessels. The Mann-Whitney test showed no significant difference (p = 1.000) between the experimental and the control groups. Conclusion: In the animal model used, dentin hypersensitivity does not trigger dental pulp inflammatory response.

Protective Effect of Curcumin Against Hepatic Toxicity Induced by Lithium Carbonate (Li2 Co3)

The current work was done on four groups of rats (10 for each) to detect the hepato-protective characters of curcumin on the toxicity induced by lithium carbonate. The oral administration of Li2 Co3 for one-month lead to noticeable decrease in the SOD, CAT and GSH while the increase in the GPx and some histological changes in the portal tissues including hydropic degeneration and thickening in the wall of the veins with numerous vacuolar degenerations were detected in most of the liver cells. Haemorrghic, edematous blood vessels were noticed in the portal tissues. Focal areas of lymphocytic infiltration were located around the congested blood vessels and spread between the liver hepatic cords. Noticeable significant elevation of total chromosomal structure aberrations (a centaromeric, dicentric, break, fragment, deletion, sticky, end to end and ring) and total chromosomal numerical aberrations (hypoploidy, hyperploid and polyploidy). While the pre-treatment with curcumin lead to improvement of the hepatic architecture and biochemical parameters. Also diminish of all chromosomal structure aberrations and all chromosomal numerical aberrations were noticed after treatment with curcumin. Curcumin can prevent the hazard effect of lithium carbonate on liver tissue.

Effect of taxifolin on oxidative gastric injury induced by celiac artery ligation in rats

Purpose: To examine the effect of taxifolin on I/R induced gastric injury in rats using biochemical and histopatholohical methods. Methods: Eighteen albino Wistar male rats equally grouped as; gastric I/R (I/R), 50 mg/kg taxifolin + gastric I/R (TAX+ I/R) and sham operation applied (SHAM). Ischemia induced for 1 hour, and reperfusion induced for 3 hours. Results: Oxidant parameters like, Malondialdehyde (MDA) and Hydroxyguanine (8-OHdG) were higher, whereas total glutathione (tGSH) was lower in the I/R group according to SHAM group, histopathological findings such as marked destruction, edema, and proliferated dilated congested blood vessels were observed severely in the I/R group, whereas there was not any pathological finding except mild dilated congested blood vessels in the TAX+ I/R group. Conclusion: The taxifolin can be clinically beneficial in the treatment of gastric injury due to I/R procedure.

Benidipine can prevent liver ischemia reperfusion injury in rats: a biochemical and histopathological evaluation

Ischemia reperfusion (IR) injury is defined as a pathological process which initiates with tissue deoxygenation, continues with oxidative stress, and spreads with inflammation. Increased intracellular calcium is responsible for oxidative stress and inflammation during this process. Benidipine is an antihypertensive drug acting as an T/L-type calcium channel blocker. The effect of benidipine on cyclooxygenase-2 (COX-2) activity is not known. Benidipine being a calcium channel blocker suggests that it may suppress oxidant and proinflammatory COX-2 production. The aim of this study was to examine the effect of benidipine on IR induced liver injury in albino Wistar male rats. Animals were divided into three groups: liver ischemia reperfusion (LIR), 2 mg/kg benidipine + liver ischemia reperfusion (BLIR), and sham surgery (SHAM). Hepatic artery, portal vein and bile duct were clamped to obtain ischemia for one hour and reperfusion for six hours. Malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and COX-2 levels were higher, whereas total glutathione (tGSH) and cyclooxygenase-1 (COX-1) levels were lower in the LIR group. Liver tissue of the LIR group showed marked dilated congested blood vessels and increased bile duct proliferation, polymorphonuclear leukocyte infiltration, edema, hemorrhage and destruction. MDA, ALT, AST and COX-2 levels were lower, and tGSH and COX-1 levels were higher in the BLIR group treated with benidipine. Liver tissue of the BLIR group was found to be normal except for mild dilated blood vessels. These experimental findings indicate that benidipine may be useful in the treatment of liver IR injury.

Raspberry ketone and Garcinia Cambogia rebalanced disrupted insulin resistance and leptin signaling in rats fed high fat fructose diet

AimObesity is a continually growing pandemic leading to many diseases that affect the overall quality of life. The widely marketed Garcinia cambogia (GC) and Raspberry ketone (RK) were used in this study. Despite their known dietetic effect, however, the metabolomic/signaling pathways involved in this effect are not fully elucidated. Hence, our study comprehends the possible trajectories of their combination against obesity and insulin resistance in addition to exploring their combination merit. Materials and methodsAdult male Wistar rats were divided into 5 groups; viz., normal diet (ND), high fat fructose diet (HFFD), HFFD+GC (600mg/kg), HFFD+RK (55mg/kg) and HFFD+GC+RK. To assess our aim, we determined their effect on body weight, IPGTT, glucose homeostasis (glucose, insulin, HOMA IR), lipid profile parameters and SREBP-1c, oxidative stress markers, insulin and leptin signaling pathways (p-IRS-1/p-AKT/GLUT-4, and leptin/STAT-3), as well as liver and adipose tissue histopathology. ResultsGC/RK combinationcaused weight loss, corrected the disturbed glucose and insulin homeostasis, raised serum levels of HDL anddecreased all other lipid profile parameters. They also increased Nrf-2 expression, ad GSH, as well as p-IRS-1/p-Akt/GLUT-4 cue, while they decreased MDA, leptin/STAT-3 and SREBP-1c content compared to the HFFD group. Furthermore, the GC/RK combination abolished apoptosis, fatty changes and inflammation in hepatocytes and decreased sclerotic blood vessels and congestion in adipose tissue. ConclusionOur study highlights the involvement ofp-IRS-1/p-Akt/GLUT-4, leptin/STAT-3 and SREBP-1c signaling trajectories in the beneficial combination of GC and RK, besides, the efficient rebalance of the redox status, insulin resistance and tissue fat deposition confirmed histopathologically.

HEPATIC AND RENAL HISTOPATHOLOGICAL AND ULTRASTRUCTURAL ALTERATIONS FOLLOWING EXPOSURE TO DIFFERENT GOLD NANOPARTICLE SIZES IN FEMALE PREGNANT RATS.

Nanoparticles (NPs) not only offer a great possibility for biomedical application, pharmaceutics, but also may be used for novel diagnostic and therapeutic approaches. Currently, there are no data available regarding to what extent the degree of toxicity of gold nanoparticles (AuNSs). This study aimed to investigate the histopathological and ultrastructural effect of AuNSs size on the liver and kidney of female pregnant rats. To achieve that gold nanoparticles of 10 nm, 25nm and 50 nm were Interperitoneally injected in female rats at 48 hr during rat pregnancy. Forty adult female albino rats were divided into four equal groups: The first one served as a control group, the second received 75 mg/kg/day AuNSs as 10 nm in size, the third received 75 mg/kg/day AuNSs as 25 nm in size and the fourth received 75 mg/kg/day AuNSs as 50 nm in size, All groups were scarified after 19days from gestation where liver and kidney specimens were collected at the end of the experiment for histological and ultrastructural examination, AuNSs treated groups revealed wide spread histological and ultrastructural alterations in the liver and kidney structure as dilated and congested hepatic blood vessels, widespread vacuolated and ballooned hepatocytes with early apoptotic changes, pyknotic hyper chromatic irregular nuclei with deteriorated chromatin condensation. The distal convoluted tubule had shrunken pyknotic nuclei and margination of heterochromatin with irregular nuclear envelope. This study conculcated that all size of AuNSs caused side effect in the liver and kidney of pregnant rates.

THE BENEFICIAL ROLE OF VITAMIN D AND COCONUT OIL IN ALLEVIATING THE BLOOD GLUCOSE AND INSULIN LEVELS AND HISTOLOGICAL ALTERATIONS IN THE THYROID GLANDS OF HYPERGLYCEMIC MICE

The purpose of the present study is to evaluate the effects of either vitamin D or coconut oil or both together on the histological changes of the thyroid glands of diabetic adult male mice (Mus musculus) induced by using streptozotocin (STZ). The mice were divided into 7 equal groups (10 mice/each). The duration of the experiment was 4 weeks. Group I: normal control mice, a group without any treatments. Groups II and III: non-diabetic mice groups received vitamin D orally in a daily dose of 500 IU (6.25 ml/kg body weight) or coconut oil (7.5 ml/kg body weight/day), respectively. Group IV: diabetic mice group injected intraperitoneally with a single dose of STZ dissolved in saline solution in a dose of 200 mg/kg body weight to induce diabetes. Groups V, VI and VII: diabetic mice administered orally with vitamin D or coconut oil or both together with the same previous doses. The results recorded non-significant changes in the blood glucose, insulin levels of non-diabetic mice groups received either vitamin D or coconut oil. A high significant increase in blood glucose level and a significant decrease in insulin were found in the diabetic mice group as compared to the normal control ones. Diabetic mice group received the vitamin D only recorded a slight decrease in blood glucose level and a slight increase in insulin; while the diabetic mice received coconut oil alone or co-administered with vitamin D recorded a significant decrease in blood glucose levels and a significant increase in insulin as compared to diabetic group. Histologically, the mice of normal control group or that received either vitamin D or coconut oil showed the normal structure of thyroid follicular cells. Each follicle consists of a layer of simple cuboidal epithelial cells with spherical densely-stained nuclei, and its cavity contains vacuolated acidophilic colloid. The diabetic mice demonstrated many histopathological changes in the thyroid included vacuolated thyrocytes, enlargement of numerous follicles that were filled with colloids, and others demonstrated fusion between them. The appearance of dilated and congested blood vessels in the interstitia between the follicles was also seen. The diabetic mice administered with vitamin D elucidated little improvement in the thyrocytes, while that received either coconut oil alone or co-administered with vitamin D illustrated a marked recovery in the structure of the thyrocytes with normal nuclei similar to the control form. In conclusion, diabetic mice received either coconut oil alone or co-administered with vitamin D demonstrated stronger anti-hyperglycemic effects to recovery the glucose and insulin rates to normal levels, and restored the histological architecture of the thyroid glands to approximately the normal status than those given vitamin D only.

Effects of nitrate on aquaculture production, blood and histological markers and liver transcriptome of Oplegnathus punctatus

Nitrate, the end-product of nitrification, tends to accumulate in recirculating aquaculture systems (RASs). We investigated the 96-h acute and 28-d chronic toxicity of nitrate-N to spotted knifejaw, Oplegnathus punctatus. We exposed juveniles (1.3 ± 0.6 g, 2.3 ± 0.7 cm TL) to seven different nitrate-N concentrations (11.3 (control), 673.1, 873.9, 1052.9, 1471.1, 1887.1, or 2368.3 mg/L) in a triplicated experimental design for 96 h; the estimated LC50 values for nitrate-N at 24, 48, 72, and 96 h were 774.4, 678.8, 586.3, and 484.5 mg/L nitrate-N − N, respectively. In an examination of chronic effects of elevated nitrate-N, juvenile O. punctatus (44.9 ± 7.0 g; 7.3 ± 0.6 cm) were exposed to 21.4 ± 4.4 mg/L (treatment 1), 165.5 ± 7.8 mg/L (treatment 2), or 299.4 ± 5.8 mg/L (treatment 3) nitrate-N in triplicated RASs, and the impact of nitrate-N on performance, blood, histological, and gene expression markers was evaluated. After 28 days, final length, specific growth rate and feed conversion ratio did not differ (p > .05) among treatments. Final weight and mortality did not differ significantly between treatments 1 and 2, but was significantly (p < .05) different in treatment 3. Red blood cell count, white blood cell count, and plasma hemoglobin concentration were significantly (p < .05) lower for fish in treatment 3, and plasma nitrate-N concentration was higher. Plasma cortisol concentrations did not differ significantly among treatments. At the histological level, telangiectasia, hyperplasia, and lamellar shortening and fusion were observed in the gills of fish in treatments 2 and 3; blood congestion was observed in the sinusoids of liver and the hepatocytes exhibited vacuolation and atrophy. RNA-seq showed differential expression of genes in liver (p < .05) among treatments 1, 2, and 3. Gene ontology and assessment of relevant molecular pathways showed the involvement of the Wnt signaling pathway in fish response to nitrate-N exposure. Transcriptome analysis identified important stress response-related genes and signaling pathways that provide insights into mechanisms of response to nitrate-N toxicity. Our findings showed chronic health impacts upon juvenile Oplegnathus punctatus at 165 mg/L nitrate-N, and we recommend further toxicity trials at lower levels to inform prevention of chronic nitrate toxicity.

Acute pulmonary effects of aerosolized nicotine.

Nicotine is a highly addictive principal component of both tobacco and electronic cigarette that is readily absorbed in blood. Nicotine-containing electronic cigarettes are promoted as a safe alternative to cigarette smoking. However, the isolated effects of inhaled nicotine are largely unknown. Here we report a novel rat model of aerosolized nicotine with a particle size (~1 μm) in the respirable diameter range. Acute nicotine inhalation caused increased pulmonary edema and lung injury as measured by enhanced bronchoalveolar lavage fluid protein, IgM, lung wet-to-dry weight ratio, and high-mobility group box 1 (HMGB1) protein and decreased lung E-cadherin protein. Immunohistochemical analysis revealed congested blood vessels and increased neutrophil infiltration. Lung myeloperoxidase mRNA and protein increased in the nicotine-exposed rats. Complete blood counts also showed an increase in neutrophils, white blood cells, eosinophils, and basophils. Arterial blood gas measurements showed an increase in lactate. Lungs of nicotine-inhaling animals revealed increased mRNA levels of IL-1A and CXCL1. There was also an increase in IL-1α protein. In in vitro air-liquid interface cultures of airway epithelial cells, there was a dose dependent increase in HMGB1 release with nicotine treatment. Air-liquid cultures exposed to nicotine also resulted in a dose-dependent loss of barrier as measured by transepithelial electrical resistance and a decrease in E-cadherin expression. Nicotine also caused a dose-dependent increase in epithelial cell death and an increase in caspase-3/7 activities. These results show that the nicotine content of electronic cigarettes may have adverse pulmonary and systemic effects.