Role of Quercetin against the Effect of Piroxicam on the Liver and Kidney in Pregnant Rats

Background and Objectives: We evaluated the impact of the second-generation macrolide azithromycin on pregnant albino rats' livers and assessed the protective role of folic acid. Materials and Methods: For this study, forty pregnant rats were treated and then examined. Forty pregnant albino rats were divided into four equal groups (I-IV). In Group I, each pregnant rat was gavaged with 1 mL distilled water on day 16 of pregnancy, then 0.5 mL from day 16 of pregnancy to day 20. In Group II, each pregnant rat was gavaged with 0.45 mL distilled water containing 9 mcg folic acid from day 17 of pregnancy to day 20. In Group III, each pregnant rat was gavaged with 1 mL distilled water containing 9 mg azithromycin on the 16th day, then 0.5 mL distilled water containing 4.5 mg azithromycin from day 17 of pregnancy to day 20. In Group IV, each pregnant rat was gavaged with 1 mL of distilled water containing 9 mg azithromycin and 0.45 mL distilled water containing 9 mcg folic acid on the 16th day, then 0.5 mL of distilled water containing 4.5 mg azithromycin and 0.45 mL distilled water containing 9 mcg folic acid from day 17 of pregnancy to day 20. At the end of the experiments, blood samples and the livers of the studied groups were subjected to biochemical, histological, and morphometric analysis. Results: Azithromycin induced pathological changes in the livers, as evidenced by disturbed lobular architecture, cytoplasmic vacuoles, deeply stained hepatic nuclei, and elevated liver enzymes. The co-administration of folic acid ameliorated most pathological changes. Conclusions: Azithromycin caused pathological alterations in the livers of pregnant rats, and the co-supplementation of folic acid with azithromycin is encouraged, to minimize these changes.

Comparison of the effects of N-nitrosodimethylamine on pregnant and nonpregnant Holtzman rats

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.

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.

Pregnant and nonpregnant rats were treated with 37.5 mg phenobarbital (PB) per kg body weight twice daily for 4 days. Pregnant rats were injected with PB from day 10 to day 13 and from day 17 to day 20 of gestation and were used for the experiments on day 14 or day 21, respectively. This treatment resulted in a 35% increase in liver weight in nonpregnant rats. The livers of pregnant rats weighed the same as the livers from PB-treated nonpregnant rats, and PB-treatment during gestation had only a small stimulatory effect on liver weight.—The duration of sleeping time after an i.p. injection of 125 mg hexobarbital per kg maternal body weight was identical in control nonpregnant and control pregnant rats. PB-treatment significantly reduced the sleeping time but PB-treated pregnant rats had a longer sleeping time than PB-treated nonpregnant rats.—In liver microsomes, the K m and V max values were measured for the ethylmorphine N-demethylase and benzo(a)pyrene hydroxylase. For the two substrates the K m values were identical in all groups. The V max values for the two enzyme activities were not different in control pregnant and control nonpregnant rats when calculated per total liver. Treatment of the rats with PB increased the V max values for the two enzyme activities, but these values were significantly lower in the microsomes obtained from PB-treated pregnant rats.—The content of cytochrome P-450 was higher in PB-treated nonpregnant rats than in control nonpregnant rats, but no increase in the amount of cytochrome P-450 was measured after treating pregnant rats with PB.—The electron microscopic examination of the livers of pregnant rats revealed that the smooth elements of the endoplasmic reticulum were predominant in the cytoplasm, and after PB-treatment the typical proliferation of the smooth ER was not detectable.

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.

We have assessed the effects of the broad-spectrum bactericide triclosan on the liver of pregnant albino rats and their offspring, and evaluated the protective potential of bee honey, which has radical-scavenging properties. The study involved treatment of 72 pregnant rats followed by examination of the pregnant rats and their offspring. The pregnant rats were divided equally into six groups (I-VI), each of which was subdivided equally into two Subgroups (A and B). Rats in the A subgroups were gavaged with a daily dose of 1.26 ml distilled water (IA), 1 ml corn oil (IIA), 1.68 ml aqueous solution of Clover Blossom honey (IIIA), 0.3 mg triclosan (IVA), 13 mg triclosan (VA), or 1.68 ml aqueous solution of honey with 13 mg triclosan (VIA), throughout pregnancy. Rats in the B subgroups received the same treatments throughout pregnancy and for 14 days after delivery. At the end of the experiments, the offspring's numbers were recorded and blood samples were taken from the pregnant rats for analysis. The livers of the studied groups were subjected for; histological study, morphometric analysis, and biochemical estimation of markers of oxidative stress. The results showed that the acceptable daily intake of triclosan did not induce significant pathological changes in the liver while high dose of triclosan induced pathological changes in the livers and reduced the numbers of offspring. Co-administration of honey with triclosan ameliorated most pathological change. Therefore, decrease the exposure of the pregnant women to triclosan is encouraged or co-supplementation with bee honey if exposure could not be avoided.

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.

Receptors specific for lactogenic hormones were solubilized by 1% (v/v) Triton X-100 from the crude particulate membrane fraction of livers of pregnant and non-pregnant female rats and the characteristics of both preparations were compared. Human (125)I-labelled somatotropin was used for binding studies of lactogenic hormone. The solubilized receptor retained most of the characteristics noted in the particulate fraction. The binding of human (125)I-labelled somatotropin to the solubilized receptor is a saturable process, depending on temperature and time. Scatchard analysis of displacement curves revealed similar affinity constants ranging from 1.02 x 10(9) to 1.20 x 10(9) 1/mol, while the binding capacity was 4.5 times greater in the pregnant rat livers than in the non-pregnant female rat livers. The receptors for human (125)I-labelled somatotropin from livers of non-pregnant and pregnant female rats were equally adsorbed onto a concanavalin-A-Sepharose column and were dissociated from the column with alpha-methyl-d-glucoside or alpha-methyl-d-mannoside in the same manner. By gel filtration on Sepharose 6B, however, the molecular sizes of the hepatic receptors were found to be different. The apparent M(r) value was approx. 270000 with a Stokes' radius of 5.5nm in the non-pregnant female rats and approx. 330000 with a Stokes' radius of 5.5nm in the pregnant rats. Furthermore, isoelectric-focusing experiments showed that a major part of the receptor from the non-pregnant female rat livers had a neutral pI (7.0-8.5), whereas that from pregnant-rat livers had an acidic pI (4.2-4.7). These data suggest that the increase in the lactogenic binding capacity in rat liver membranes during pregnancy may be associated with marked changes of the physicochemical properties of the receptors.

Levetiracetam is a broad-spectrum antiseizure agent and one of the most commonly prescribed drugs for epilepsy. The aim of this work was to assess the effect of levetiracetam at its therapeutic range on the liver and kidney of pregnant albino rats. Forty pregnant rats were divided equally into two groups (I-II), Rats in the group I were gavaged 1.5 mL/day distilled water in two divided doses throughout pregnancy. Rats in the group II were gavaged 1.5 mL/day distilled water (containing 36 mg levetiracetam) in two divided doses throughout pregnancy. At the end of the experiment, blood samples were taken and the sera were separated and used for biochemical analysis. The kidneys and livers of both groups were excised and used for light and electron microscopic examination. Treatment with levetiracetam induced undesirable histopathological changes in the liver and kidney of pregnant albino rats. These changes were in the form of distortion of the hepatic architecture, dilatation of the central and the portal veins, widening of the Bowman's spaces, thickening and disruption of the glomerular basement membrane, fusion and effacement of secondary foot processes, cytoplasmic vacuolation, and swollen mitochondria with loss of their cristae. Such changes were confirmed by alteration of certain biochemical parameters related to the liver and kidney functions. Levetiracetam induced deleterious effects on the liver and kidney of pregnant albino rats. Further investigations are recommended to clarify the mechanism of levetiracetam toxicity.

Mesenchymal stem cells (MSCs) are multipotent stromal cells with remarkable plasticity, enabling them to differentiate into various tissue-specific cell types. MSCs play a pivotal role in tissue repair, hematopoiesis and immunomodulation. This study aimed to evaluate and compare the protective effects of olive leaf extract (OLE), bone marrow-derived mesenchymal stem cells (BM-MSCs) and their combination against hepatic and splenic toxicity in a rat model of gestational diabetes induced by streptozotocin (STZ). Histopathological and immunohistochemical analyses of liver and spleen tissues were conducted to assess these effects. Methods: Pregnant female rats were divided into five groups (n = 10 per group): Control group: Rats received STZ at a dose of 35 mg/kg body weight. OLE group: Rats were administered olive leaf extract (OLE) at 200 mg/kg body weight. GD + OLE group: Rats with STZ-induced gestational diabetes (GD) were treated with OLE (200 mg/kg body weight). GD + MSCs group: Rats with STZ-induced GD were treated with BM-MSCs. GD + OLE + MSCs group: Rats with STZ-induced GD were treated with both OLE and BM-MSCs. Results: STZ administration induced significant histopathological and immunohistochemical alterations in the liver and spleen tissues of pregnant femal rats. Treatment with OLE, BM-MSCs, or their combination markedly ameliorated these STZ-induced deteriorations, with the combined treatment showing the most pronounced protective effects. Conclusion: The findings demonstrate that both BM-MSCs and OLE exert protective effects against hepatotoxicity and splenic toxicity in a rat model of gestational diabetes. The combination of OLE and BM-MSCs exhibited synergistic benefits, highlighting their potential as therapeutic agents for mitigating organ damage in gestational diabetes.

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Background: Carbamazepine (Tegretol) is an anticonvulsant and mood stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia. It has been assigned to pregnancy category D by the U.S Food and Drug Administration (FDA). CBZ can cause fetal harm when administered to pregnant women. Epidemiological data suggested that there may be an association between the use of CBZ during pregnancy and congenital malformations, specifically spina bifida and developmental disorders. The possible malformation-specific risks with CBZ use during pregnancy need to be considered, so the present work was conducted to evaluate the genotoxicity of two doses of CBZ (3.6 mg and 10.8 mg/ 100g body weight/ day) in pregnant female rats and their fetuses. Chromosomal aberration in bone marrow cells and histopathological examination of liver and kidney of pregnant rats were also determined. Materials and Methods: Fourty five pregnant Sprague Dawley rats were randomly divided into the groups. The first was administered oral doses of distilled water and served as control. The other two groups were administered oral doses of CBZ suspended in distilled water equivalent to 3.6 mg and 10.8 mg/100g body weight/day respectively for 15 day from the 6th day to the 20th day of gestation. Females were sacrificed on the 20th day of gestation. Results: Administration of CBZ 3.6 mg and 10.8 mg /100g body weight to pregnant rats from the 6th till the 20thday of gestation. Decreased fetal body weight, crown-rump length, increased resorbed and dead fetuses were observed compared to the control ones. Moreover, CBZ-high dose group(10.8mg/100g) causedmalformations that could be described as severe growth retardation. At the same time, bone marrow metaphases of CBZ-treated pregnant rats revealed structural chromosomal aberrations. Whereas, histopathological examination of liver and kidney of pregnant rats treated with both doses of CBZshowed cellular alterations.Conclusion:It has been found that usage of antiepileptic CBZ during gestational period may create risk, associated with maternal toxicity, hepato- and nephrotoxicity and chromosomal aberrations in pregnant rats, with intrauterine growth retardation which was manifested by low body weight, length reduction and malformations. These alterations were dose dependent. The benefits of taking CBZ must be weighed against the potential risks to boththe developing fetus and the mother.

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.

Hepatocytes from pregnant rats fasted during late gestation are larger and more abundant than in littermate virgin animals and in vivo are exposed to hypoglycemia. To evaluate their intrinsic potential for biosynthetic transformations of alanine, a modified liver perfusion system was employed. Livers from twenty-four hour fasted, nineteenday pregnant and virgin littermate rats were subjected to “wash out” perfusion for twenty-five minutes prior to definitive perfusion for sixty minutes with fresh media containing supramaximal amounts of L-alanine-14-C (17 mM). Under such conditions, livers from pregnant rats displayed an enhanced capacity to assimilate alanine-14-C and to establish concentration gradients for alanine between hepatocytes and perfusion medium. Significantly more alanine carbons were incorporated into glucose, lactate, glyceride-glycerol, and glutamate per hepatocyte by livers of pregnant rats. Clyceride-glycerol formation was disproportionately enhanced suggesting that there may be mechanisms operative during pregnancy for selectively diverting triose phosphates toward the esterification of intrahepatic fatty acids. Despite the augmented disposition of alanine carbons, livers from pregnant animals formed significantly less urea. Instead, a much greater proportion of the nitrogen derived during alanine catabolism was released in a potentially reutilizable form, ammonia. Thus, hepatocytes from fasted pregnant animals have an enhanced capacity for assimilating “loading” doses of alanine and for incorporating the carbons into glucose, lactate, glyceride-glycerol, and glutamate, while preserving more of the amino nitrogen in a form that can be reutilized.