Liver Of Pregnant Rats Research Articles

Pregnancy alters fatty acid metabolism, glucose regulation, and detoxification of the liver in synchrony with biomechanical property changes

Pregnancy places a metabolic burden on the body including the liver, which is responsible for ensuring adequate nutrition for the maternal and fetal systems. To gain a better understanding of liver adaptation, this study investigates metabolic shifts occurring in livers of pregnant rats. Metabolic capacities of the livers of pregnant and non-pregnant female Wistar rats were assessed using comprehensive metabolic models. Kinetic metabolic models were generated for each animal based on protein abundance data from proteomics analysis allowing for a subject-specific assessment of hepatic metabolic functions. Data are available via ProteomeXchange with identifier PXD050758. Additionally, tissue stiffness, viscosity, and water diffusion obtained from magnetic resonance imaging and elastography were correlated with metabolic capabilities to study the relationship between metabolic function and biophysical properties. Proteome profiling revealed differences in protein expression in the livers of pregnant and non-pregnant animals. Functional analysis showed significant variations in metabolic capacities. Livers of pregnant rats had reduced capacities in carbohydrate and fatty acid metabolism, along with altered urea synthesis. Additionally, there were associations between metabolic functions and biophysical properties highlighting potential links between changes in liver structure and metabolic capacities during pregnancy. In summary, our work reveals extensive hepatic metabolic changes in pregnant rats. The liver adapts its metabolic capacities to ensure whole-body metabolic homeostasis but may struggle to counteract nutritional challenges, such as hypoglycemia. The study, employing a personalized approach combining proteomics, kinetic modeling, and advanced imaging, sheds light on the intricate interplay between hepatic adaptations and medical imaging markers, providing a foundation for further investigations into the implications for maternal and fetal health.

Core biomarkers analysis benefit for diagnosis on human intrahepatic cholestasis of pregnancy

BackgroundThe pregnant women with intrahepatic cholestasis were at high risk of fetal distress, preterm birth and unexpected stillbirth. Intrahepatic cholestasis of pregnancy (ICP) was mainly caused by disorder of bile acid metabolism, whereas the specific mechanism was obscure.MethodsWe performed proteomics analysis of 10 ICP specimens and 10 placenta specimens from patients without ICP through data-independent acquisition (DIA) technique to disclose differentially expressed proteins. We executed metabolomic analysis of 30 ICP specimens and 30 placenta specimens from patients without ICP through UPLC-MS/MS to identify differentially expressed metabolites. Enrichment and correlation analysis was used to obtain the direct molecular insights of ICP development. The ICP rat models were constructed to validate pathological features.ResultsThe heatmap of proteomics analysis showed the top 30 up-regulated and 30 down-regulated proteins. The metabolomic analysis revealed 20 richer and 4 less abundant metabolites in ICP samples compared with placenta specimens from patients without ICP, and enrichment pathways by these metabolites included primary bile acid biosynthesis, cholesterol metabolism, bile secretion, nicotinate and nicotinamide metabolism, purine metabolism and metabolic pathways. Combined analysis of multiple omics results demonstrated that bile acids such as Glycohyocholic acid, Glycine deoxycholic acid, beta-Muricholic acid, Noncholic acid, cholic acid, Gamma-Mercholic Acid, alpha-Muricholic acid and Glycochenodeoxycholic Aicd were significantly associated with the expression of GLRX3, MYL1, MYH7, PGGT1B, ACTG1, SP3, LACTB2, C2CD5, APBB2, IPO9, MYH2, PPP3CC, PIN1, BLOC1S1, DNAJC7, RASAL2 and ATCN3 etc. The core protein ACAT2 was involved in lipid metabolic process and animal model showed that ACAT2 was up-regulated in placenta and liver of pregnant rats and fetal rats. The neonates had low birth weight and Safranin O-Fast green FCF staining of animal models showed that poor osteogenic and chondrogenic differentiation of fetal rats.ConclusionMultiple metabolites-alpha-Muricholic acid, beta-Muricholic acid, Glycine deoxycholic acid and Glycochenodeoxycholic Acid etc. were perfect biomarkers to predict occurrence of ICP. Bile acids were significantly associated with varieties of protein expression and these proteins were differentially expressed in ICP samples. Our study provided several biomarkers for ICP detection and potential therapeutic targets for ICP development.

Comparative characterization of liver morphometric parameters during pregnancy in experimental chronic renal failure

Study of morphological and morphometric changes of the liver of pregnant white rats after chronic renal failure. [9]. A study of normal morphological and morphometric parameters of the liver of pregnant white rats. Study of the anatomical parameters of the liver of purebred rats in pregnancy and its reactive changes after experimental chronic renal failure Comparison of pregnancy-related histo-topographic features of the liver of purebred rats in experimental chronic renal failure with parameters of healthy rats; [10]. Comparative classification of morphometric changes in the liver of pregnant rats after correction with Juyzar waters in experimental chronic renal failure.Glomerulopathies: focal glomerulosclerosis, membranous and membranous-proliferative glomerulonephritis, the damage of kidney balls is reduced in the primary order. Due to the alteration of the basal membrane of the glomerulus, increased permeability leads to proteinuria. [17]. Prolonged proteinuria results in decreased albumin in the blood plasma (Hypoalbuminemia). The quality of albumin and globulin changes. A decrease in albumin leads to a decrease in osmotic pressure. The passage of fluid from the blood to the tissue increases. The function of sodium and potassium pumps is disturbed. Swelling develops. At the same time, the reduction of albumin leads to an increase in the synthesis of lipoproteins. [16]. This has an effect on the oncotic pressure. The release of a large amount of lipids in the urine is a sign that the permeability of the glomerular basement membrane has changed.

The effects of a high-fat diet on the liver of pregnant albino rats and their developing offspring

ABSTRACT Studies have demonstrated that the consumption of a high-fat diet (HFD) is linked to a higher occurrence of obesity and metabolic disorders. Maternal dietary habits can have long-lasting effects on the health of offspring. This study aimed to evaluate the impact of a HFD on the liver of pregnant rats and their offspring. 30 pregnant rats were used in this study. They were divided into two equal groups; control and HFD group. HFD group were fed on 15% lard from 6th week before conception till the end of weaning period. The mother rats and their offspring were sacrificed; blood samples were collected for estimation of biochemical parameters. The liver was removed for histological, immunohistochemical, and ultrastructural investigations. HFD mothers displayed elevated serum levels of LDL, triglycerides and total cholesterol and elevated blood glucose compared to the control. Also, remarkable histopathological and ultrastructural signs were recorded in the liver tissue of HFD treated mothers and their offspring. Additionally, the liver tissue displayed strong expression for caspase 3 and obvious reduction for PCNA. These results emphasize the importance of a balanced diet during pregnancy to prevent long-term liver complications in both mothers and their offspring.

Morphological, biochemical, and histopathological effects of levetiracetam on pregnant albino rats and their offspring

ABSTRACT One of the most widely used medications for epilepsy is the broad-spectrum antiseizure levetiracetam. The study aimed to evaluate the impact of levetiracetam on the bodyweight and liver of pregnant rats and their offspring. The study involved treating the rats during pregnancy and lactation and then examining the pregnant rats and their offspring. Two groups of 40 pregnant rats were created (I, II). Each group was split up into two smaller groups (A, B). About 1.5 mL/day of distilled water was gavaged to the rats in group I, either continuously throughout pregnancy (IA) or continuously throughout pregnancy and 15 days after delivery (IB). Group II rats received 1.5 ml/day of distilled water (containing levetiracetam) either during pregnancy (IIA) or during pregnancy plus 15 days postpartum (IIB). At the end of the work, blood samples were taken from the adult rats, body weight of different groups were recorded, and then, their liver was subjected for histological and morphometric analysis. Levetiracetam treatment showed reduction in the body weight of adult rats and their offspring and pathological changes in their liver. These changes were in the form of distortion of the hepatic architecture, cytoplasmic vacuolation, nuclear changes, and swollen mitochondria with loss of their cristae. Such changes were proved by alteration in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme levels of the liver. It is advised to monitor the liver functions continuously when using levetiracetam.

Nerolidol Attenuates Diabetic Embryopathy in Streptozotocin-induced Diabetic Pregnant Rats by Reducing Embryonic and Maternal Oxidative Stress

Background Pregnancy complicated by diabetes leads to congenital disorders, spontaneous abortion, and neonatal morbidity and mortality, which are termed diabetic embryopathy or fetopathy. Objectives In this work, we planned to investigate the therapeutic potentials of nerolidol against streptozotocin (STZ)-induced diabetic embryopathy in rats through attenuating maternal and fetal oxidative stress. Materials and Methods The male and female Wistar rats were allowed to mate for a night at a 1:1 ratio. After the confirmation of pregnancy, the rats were administered 40 mg/kg of STZ (i.p.) to initiate diabetes and treated with 20 and 40 mg/kg of nerolidol. The changes in food intake, body weight, blood glucose, and urine output were regularly monitored. The levels of lipid profiles were estimated using assay kits. The oxidative stress and antioxidant biomarkers in the liver tissues and embryonic fractions were measured using assay kits. Results The nerolidol treatment considerably depleted the blood glucose and urine output and augmented the body weight and diet intake in diabetic rats. The nerolidol suppressed the cholesterol (Ch), triglycerides (TG), and very low density lipoprotein (VLDL) and elevated the high density lipoprotein (HDL) level in diabetic pregnant rats. The maternal and embryonic oxidative stress levels are effectively reduced by the nerolidol treatment by decreasing the malondialdehyde (MDA) and reactive oxygen species (ROS) levels. The levels of antioxidants were also increased by the nerolidol on both liver and embryonic fractions of diabetic pregnant rats. Conclusion Our results exhibited that the nerolidol treatment considerably reduced embryonic and maternal oxidative stress and embryonic deaths. Hence, it can be a hopeful therapeutic candidate to treat diabetic embryopathy.

Toxicity of Propylene Glycol Extract of Propolis on Central Nervous System and Liver in Pregnant and Neonatal Rats.

Propolis has become one of the most preferred supplements due to its beneficial biological properties. Organic (water and vegetable oils) and chemical (ethyl alcohol, propylene glycol, and glycerol) solvents are used for propolis extraction. However, the effects of these chemicals on health should be taken into account. In this study, the effects of propolis extracts on health were evaluated. 32 pregnant Wistar albino rats and 64 neonatal/young adults were given three different extractions of propolis (propylene glycol, water, and olive oil). Histopathological analyses were performed on the liver and brain, and blood samples were taken from the hearts of rats. Histopathological scoring showed that the intensity of pycnotic hepatocyte, sinusoidal dilatation, and bleeding was high in liver samples of pregnant and baby rats given propylene glycol extract of propolis (p<0.05). Propylene glycol extract caused dilatation of blood vessels and apoptosis of neurons in brain tissue. The histopathological score was significantly lower in liver and brain tissues of rats treated with water and olive oil extract compared to propylene propolis groups (p<0.05). Liver enzyme levels in the blood increased in propylene propolis rats (p<0.05). Histopathological changes and biochemical alterations may indicate that propylene glycol extracts of propolis are more toxic than olive oil and water extracts. Therefore, olive oil and water extracts of propolis are more reliable than propylene glycol extract in pregnant and infant rats.

Content of cytochrome P-450 in microsomal fractions of the liver of pregnant rats and their embryos

This article presents a comprehensive examination of the impact of the pesticide “dropp” on the lipid peroxidation (LPO) of microsome membranes and the levels of cytochrome P-450 enzyme within microsomal fractions of pregnant rats and their developing embryos. The study delves into the intricate biochemical responses within these biological systems following exposure to the pesticide. The research uncovers a significant intensification of NADP.Nand ascorbate-dependent lipid peroxidation in the liver microsomes of both pregnant rats and their embryos upon exposure to the “dropp” pesticide. This heightened lipid peroxidation is particularly notable on the 3rd day of pregnancy, accompanied by an elevated concentration of malondialdehyde (MDA), a marker of oxidative stress. Moreover, the study reveals a noteworthy impact of “dropp” on the content of cytochrome P-450 enzyme within the microsomal fraction of the liver in pregnant rats. This enzyme, which plays a vital role in various metabolic processes, experiences a reduction in concentration upon pesticide exposure. The effect is most pronounced on the 3rd and 19th days of pregnancy, highlighting specific time windows of vulnerability. Collectively, these findings provide a nuanced understanding of the biochemical repercussions of “dropp” pesticide exposure on the microsomal membranes and enzyme dynamics within pregnant rats and their developing embryos.

Distinct profiles of oxylipid mediators in liver, lung, and placenta after maternal nano-TiO2 nanoparticle inhalation exposure.

Nano-titanium dioxide (nano-TiO2) is a widely used nanomaterial found in several industrial and consumer products, including surface coatings, paints, sunscreens and cosmetics, among others. Studies have linked gestational exposure to nano-TiO2 with negative maternal and fetal health outcomes. For example, maternal pulmonary exposure to nano-TiO2 during gestation has been associated not only with maternal, but also fetal microvascular dysfunction in a rat model. One mediator of this altered vascular reactivity and inflammation is oxylipid signaling. Oxylipids are formed from dietary lipids through several enzyme-controlled pathways as well as through oxidation by reactive oxygen species. Oxylipids have been linked to control of vascular tone, inflammation, pain and other physiological and disease processes. In this study, we use a sensitive UPLC-MS/MS based analysis to probe the global oxylipid response in liver, lung, and placenta of pregnant rats exposed to nano-TiO2 aerosols. Each organ presented distinct patterns in oxylipid signaling, as assessed by principal component and hierarchical clustering heatmap analysis. In general, pro-inflammatory mediators, such as 5-hydroxyeicosatetraenoic acid (1.6 fold change) were elevated in the liver, while in the lung, anti-inflammatory and pro-resolving mediators such as 17-hydroxy docosahexaenoic acid (1.4 fold change) were elevated. In the placenta the levels of oxylipid mediators were generally decreased, both inflammatory (e.g. PGE2, 0.52 fold change) and anti-inflammatory (e.g. Leukotriene B4, 0.49 fold change). This study, the first to quantitate the levels of these oxylipids simultaneously after nano-TiO2 exposure, shows the complex interplay of pro- and anti-inflammatory mediators from multiple lipid classes and highlights the limitations of monitoring the levels of oxylipid mediators in isolation.

The effect of some pesticides on lipid peroxidation and on the content of cytochrome p-450 of mitochondrial membranes and liver microsomes of pregnant rats and their embryos

The article presents data obtained in experimental studies on the effect of pesticides - butylcaptax and droppa on lipid peroxidation of mitochondrial membranes and microsomes of liver cells of pregnant rats and their embryos. It has been shown that inoculation with pesticides intensifies NADP.H- and ascorbate-dependent LPO both in mitochondria and in liver microsomes of pregnant rats and their embryos. The level of MDA is higher in case of poisoning with butylcaptax on the 3rd day of pregnancy. A decrease in the content of the microsomal enzyme P-450 in the microsomal fraction of the liver of pregnant rats was also found with the introduction of butylcaptax and dropp. This decrease is more pronounced on butylcaptax poisoning on the 3rd and 19th days of pregnancy.

EFFECTS OF BISPHENOL A AND NICOTINE ON CYTOCHROME P450S IN BRAIN AND LIVER OF PREGNANT RATS

Bisphenol A (BPA), a widely used chemical, is associated with endocrine disruption through its interactions with the aryl hydrocarbon receptor (AhR). BPA crosses into the human body mostly through migration from plastic packaging into the daily diet. AhR regulates the expression of drug-metabolizing enzymes (DMEs), including numerous CYP450s, and mediates xenobiotic reactions. This study aims at examining how the expression of CYP450s expression is affected, in the brain and liver of pregnant rats, by exposure to BPA and nicotine. Pregnant female Sprague-Dawley dams were exposed to increasing doses of BPA; 0 (control), 50, 500, and 5000 g/kg/day , or in combination with nicotine; 3000 µg/kg/day, through drinking water. Brain and liver tissues were isolated after 2 weeks of exposure, and western blotting was used to assess the expression of selected protein targets. The results showed that BPA exposure decreased the expression levels of CYP1A1 and CYP1B1 in the brain (by 55% and 79% respectively). It also decreased CYP2E1 levels in the brain (by 42%), but increased its levels in the liver (by 126%). Moreover, BPA exposure decreased levels of CYP19A1 and ARNT in the liver (by 51% and 44% respectively), and decreased those of AhRR (AhR repressor) in the brain (by 28%). On the other hand, nicotine treatment exhibited an inhibitory effect with CYP1A1, CYP1B1, and AhRR in the brain (by 67%, 78%, and 13% respectively), whereas, it inhibited CYP1A1, CYP19A1, and ARNT (AhR Nuclear Translocator) in the liver (47%, 54%, and 63% respectively). In conclusion, adult brain and liver tissues showed BPA sensitivity, which disrupts CYP450s expression, and is modulated by nicotine. The observed effects could be mediated by AhR-ARNT-dependent or independent pathways, which need to be investigated further.

Effect of Omega-3 Drug and Virgin Coconut Oil in Histopathological and Molecular Changes in Liver of Experimentally Obese Pregnant Albino Rats

The study aimed to evaluate the role of omega-3 and coconut oil in the histological changes caused by obesity in the liver of pregnant obese female rats and to evaluate the molecular change by estimating the gene expression of the insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein (IGFBP-1) genes. The study used 50 albino female rats aging (90-110) and weighting (185-200gr). The experiment included two stages. First stage was to induce obesity by adding (45% fat) to the standard diet, except for the control group. In the second stage, female rats were left to mate and were divided into 5 groups (10 for each group) as follows: G1 was the Control group that remained on a standard diet, G2 was fed a high-fat diet only, G3 was orally dosed with Omega-3 (260 g/kg), G4 was orally dosed with coconut oil (200 mg/kg), G5 was orally dosed with both Omega 3 and coconut oil with the same doses. Animals were sacrificed on the 18th day of pregnancy. Histological examination of the G2 liver showed severe steatosis in hepatocytes, cellular swelling, and congestion in the central portal vein; lipid profile results showed a reduction in total Cholesterol, triglycerides, and LDL-C in the blood serum of groups treated with both omega3 and Coconut oil. Liver in the group treated with Omega 3 alone or with coconut oil showed the normal histological features of the liver tissue. The liver of the G4 group, treated with coconut oil, showed slight cloudy degeneration of some hepatocytes with individual necrosis of some of the others and congestion in the portal vein. Groups treated with omega-3 and coconut oil separately or together showed an increase in the gene expression of IGF-1 and IGFBP-1.

Hepato- and Nephro-Effect of Sphenostylis stenocarpa– Formulated Diet on Dexamethasone-Treated Pregnant Rats

This study sought to investigate the effect of Sphenostylis stenocarpa-formulated diet on hepatic and renal parameters of dexamethasone-treated pregnant rats. Sphenostylis stenocarpa were locally sourced from a market in Ado Ekiti. They were milled into powder and used in formulating feed for experimental animals. Fifteen female pregnant rats were divided in three groups of five each. Animals in group A were exposed to standard animal feed only. This served as the control group. Those in group B were exposed to Sphenostylis stenocarpa-formulated diet + 0.3 mg/kg body weight of dexamethasone, while those in group C were exposed to Sphenostylis stenocarpa-formulated diet. At the end of the eight days treatment, animals were sacrificed and blood sample, liver and kidney were collected. Exposure of pregnant rats to dexamethasone was observed to significantly (p&lt;0.05) increased the activities of plasma aspartate amino transaminase (AST) and alanine amino transferase (ALT) as well as the concentrations of plasma total protein, bilirubin, creatinine and urea when compared with those in animals in the control as well as those fed with S. stenocarpa-formulated diet only. The results further showed that pregnant rats fed with S. stenocarpa-formulated diet only had no significant difference on plasma hepatic and renal biomarkers when compared with those in the control group. The results of liver and kidney homogenates are similar to those observed in the plasma. Exposure of animals to dexamethasone adversely unhinged hepatic and renal biomarkers investigated in the study. The study also revealed that P. biglobosa seed is beneficial to the health of the liver and kidney of pregnant female rats.

High Fat High Cholesterol (HFHC) Diet Alters Liver and Uterine Histopathology in Late Pregnant Rats

The aim of the present study was to reveal the effect of the high-fat high cholesterol diet (HFHC) in pregnant rats. HFHC diet was fed to Wistar female rats 8 weeks before and after mating upto 20th day of gestation. The effect of the HFHC diet was studied by measuring body weight, fat depots, liver weight, lipid profile, fetal parameters and histopathology of liver and uterus. HFHC diet fed rats showed significant increase in the fat depots, serum and uterine tissue cholesterol level. Increased liver weight, macrovesicular fatty degeneration of liver and infiltration of inflammatory cells and cystic endometrial glands were noticed in the uterine histopathology of HFHC fed rats. However, there was no change in litter size and weight. In conclusion, feeding of a HFHC diet prior to and during pregnancy of Wistar rats led to significant change in the metabolic profile of rats, which was associated with increase in liver weight and fat depots. Further, histopathology of liver and uterus showed inflammatory changes.

Assessment of Parkia biglobosa on Hepatic and Renal Biomarkers of Dexamethasone-Exposed Pregnant Rats

Aim: This study sought to investigate its effect on hepatic and renal biomarkers of female pregnant rats.&#x0D; Place and Duration: This work was carried out in the Department of Medical Biochemistry and Department of Science Laboratory Technology, Ekiti State University, Ado Ekiti between January and June 2021.&#x0D; Methodology: Locust bean seeds were purchased from an open market in Ado Ekiti, Nigeria and were processed using standard method. Fifteen female pregnant rats were divided into three groups of five each. Animals in group A were exposed to standard animal feed only. This served as the control group. Those in group B were exposed to animal feed mixed with locust beans + 0.3 mg/kg body weight of dexamethasone, while those in group C were exposed to animal feed mixed with locust beans only. At the end of the eight days treatment, animals were sacrificed and blood sample, liver and kidney were collected.&#x0D; Results: Exposure of pregnant rats to dexamethasone was observed to significantly (p&lt;0.05) increased the activities of plasma aspartate amino transaminase (AST) and alanine amino transferase (ALT) as well as the concentrations of plasma total protein, bilirubin, creatinine and urea when compared with those in animals in the control as well as those treated with P. biglobosa only. The results further showed that administration of P. biglobosa only had no significant effect on plasma hepatic and renal biomarkers except urea which was significantly lower than those in the control group as well as those treated with dexamethasone. The results obtained from liver and kidney homogenate respectively are similar to those observed in the plasma.&#x0D; Conclusion: Exposure of animals to dexamethasone adversely unhinged hepatic and renal biomarkers investigated in the study. The study also revealed that P. biglobosa seed is beneficial to the health of the liver and kidney of pregnant female rats.

Maternotoxicity and fetotoxicity in Rattus norvegicus albinus exposed to tramadol during the late phase of pregnancy.

Tramadol, an atypical opioid, is clinically efficacious in treating moderate to severe pain. The aim of current study was to find out the toxicological effects of tramadol exposure to pregnant rats and fetuses during the late phase of pregnancy. Wistar pregnant rats were exposed to 1.25, 2.5, or 5 mg/kg/day tramadol from 14th to 20th day of pregnancy. The same therapy was given to nonpregnant rats for 7 days. The body weight, oral glucose and lipid tolerance tests, and effect on complete blood parameters in both pregnant and nonpregnant rats were determined. On 20th day, maternal placentas were excised and weighed while fetuses were observed for any deformity and growth retardation. Oxidative stress biomarkers were estimated in the liver and kidney tissue homogenates of the pregnant and nonpregnant rats while the whole fetus homogenate was processed for the same. Moreover, histopathology of the liver and kidney of pregnant and nonpregnant rats were carried out. Tramadol administration did not significantly alter the area under curve of the blood glucose and triglyceride levels in both the pregnant and nonpregnant rats. It reduced the live fetuses, placental weights, fetal length, and fetal weights. Tramadol treated pregnant rats showed significantly (p < .05) reduced red blood cells, hematocrit, hemoglobin, and platelets with reference to control group. Similarly, structural abnormalities and malfunctioning of the liver and kidney of pregnant rats were instituted; however, it did not affect the structural integrity of nonpregnant rats. A substantial (p < .001-.0001) altered glutathione and malondialdehyde levels in the fetuses, pregnant, and nonpregnant animals (tissue homogenates) at all dosage levels were indicative of tramadol induced oxidative stress. Furthermore, tramadol exposure resulted in more significant (p < .01-.001) alteration of lipid profile in the pregnant than the nonpregnant animals. Acquired results suggested the maternotoxic and fetotoxic effects of tramadol exposure during the late gestation period.

Assessment of changes in the liver of pregnant female rats and their fetuses following monosodium glutamate administration.

Monosodium glutamate (MSG) is a common flavor enhancer and stabilizer for ready-made or packaged foods. This research investigated the impact of MSG on the maternal and fetal liver. The present study was carried out on sixteen mature female Albino rats and eight male rats of reproductive age. The control group wasdissected on day 20 of gestation. MSG group was administrated MSG daily at a dosage of 1 g/5 mL/kg body weight from day 0 to day 20 of gestation. The liver function and lipid profile of the control and treated mothers were investigated in the bloodsera. The levels of nitric oxide (NO), tumor necrosis factor (TNF-α), superoxide dismutase (SOD), and reduced glutathione (GSH) activities in the liver homogenate of maternal and fetal tissue were assayed, in addition to histopathological, histochemical and immunohistochemical studies were done to the liver tissue. The activities of liver functions and lipid profile significantly altered in the treated mothers with MSG. MSG significantly reduced the SOD and reduced GSH activities in addition to the elevated TNF-α and NO in liver tissue of pregnant mothers and their fetuses. Severe histopathological alterations were observed in both maternal and fetal liver tissues of MSG-treated groups. Moreover, histochemical observations showed a reduction of total polysaccharides in the liver of pregnant rats and fetuses. A significant increase in the percentage area of positive immunoreaction for caspase 3 was observed in the liver of treated rats with MSG compared to the liver of the control. The liver of fetuses treated with MSG revealed an alteration like their mother. This study showed that during the gestational period MSG exposure resulted in several biochemical, histological, and histochemical changes in the maternal and fetal liver tissues which emphasize the toxic effect of MSG.

Transcriptional Levels of Autophagy and UPR Markers in the Brain and Liver of Pregnant Rats

Background: Pregnancy is associated with oxidative stress that results in endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Prolonged-unalleviated ER stress causes the activation of the autophagy pathway via UPR. Expression of genes encoding glucose-regulated protein 78 (GRP78) and BECLIN1 are induced in UPR and autophagy. Objectives: We studied the mRNA expression of the aforementioned genes in the liver and brain of Nulligravida versus saline and ethanol-treated pregnant rats. Methods: Control pregnant rats were orally treated with normal saline, and test animals received ethanol 250 mg/kg or resveratrol 120 mg/kg from day 1 to day 21 of gestation. Nulligravida rats treated by saline comprised the non-pregnant control group. On day 21, mRNAs encoding GRP78 and BECLIN1 were extracted from the liver and brain tissues and assessed using real-time PCR. Results: Our results showed that the level of transcripts encoding GRP78 and BECLIN1 was higher in the liver of pregnant rats compared to Nulligravida ones. Further, ethanol decreased the mRNA levels of GRP78 and BECLIN1 in the liver of pregnant rats, an effect that was reversed by resveratrol. Levels of GRP78 transcripts were decreased, and those of BECLIN1 remained unchanged in the brain of ethanol exposed pregnant rats. Conclusions: Levels of mRNAs for GRP78 and BECLIN1 are up-regulated during pregnancy. These levels are reduced in the liver of ethanol-treated rats, and resveratrol compensates these effects.

Aspectos toxicológicos da ivermectina: um estudo dos efeitos na morfologia do fígado de ratas prenhes

A Ivermectina, princípio farmacológico de um medicamento de uso veterinário possui efeito antiparasitário contra endo e ectoparasitos, é amplamente utilizada na prática veterinária. Esta droga é biotransformada no fígado, resultando em 3 metabólitos, sendo o mais importante o 24-hidroxi-metil-diidroavermectina B1. O fígado é essencial na regulação do metabolismo, na síntese de certas proteínas, servindo como local de armazenagem para certas vitaminas e ferro, degradando certos hormônios e inativando e excretando certos medicamentos e toxinas. Portanto, este trabalho teve por objetivo avaliar a morfologia dos fígados de ratas prenhes tratadas com ivermectina. Para tanto foram utilizadas 30 ratas albinas, as quais foram divididas em 3 grupos de 10 animais. Os animais foram colocados para acasalar e após a detecção da prenhez, presença de espermatozóides no esfregaço vaginal realizado na manhã do dia seguinte, sendo assim designado o primeiro dia de gestação, cada animal foi tratado com ivermectina, na dose correspondente a cada grupo durante 18 dias, com administração a cada 3 (três) dias, totalizando 6 administrações. Após esse período o fígado foi coletado, pesado em balança analítica e processado para microscopia de luz. A análise do peso relativo dos fígados das ratas prenhes e não prenhes não revelou diferença significativa entre os grupos experimentais, onde o tratamento com ivermectina nas doses de 4,0 e 8,0 mg/kg não alterou a massa relativa do fígado, nem apresentou alterações na cor, textura, consistência e hemorragias. Com relação ao estudo através da microscopia de luz, não foram observadas alterações histopatológicas.

MECHANISMS OF INFLUENCE OF UNBALANCED FEEDING ON MORPHO-FUNCTIONAL STATE OF LIVER IN PREGNANT RATS

Pathology of the organs of the hepatobiliary system is one of the leading causes of death in highly developed countries. Among various factors that can negatively affect the morphofunctional state of the liver in the mother-fetus system, the alimentary factor occupies the first place. The aim of this study was to establish the mechanisms of influence of excess nutrients in the diet on the morphology and functional state of the liver of pregnant rats. The structural and functional state of the liver of 7 rats that received an excess diet during pregnancy and 6 rats of the control group were studied. Morphological changes were manifested by uneven expression of eNOS and a positive reaction of iNOS, which was observed not only in macrophages, but also in single endotheliocytes of dilated sinusoids. Functional changes were characterized by the development of dyslipidemia in the blood serum and the accumulation of TG and NEFA in the liver tissues. The data obtained in the course of the study may indicate pronounced disorders of lipid metabolism, which can be regarded as a risk factor for the development of steatosis, liver fibrosis, atherosclerosis and type 2 diabetes mellitus.