Expression of rat hepatic multidrug resistance-associated proteins and organic anion transporters in pregnancy

The expression of hepatic multidrug resistance-associated protein (Mrp)1, 2, 3, and 6 and organic anion transporting polypeptides (Oatp)1 and 2 were examined in control and 20- to 21-day pregnant rats. Western analysis showed that expression of Oatp2 was decreased 50% in pregnancy, whereas expression of Oatp1 did not change. Expression of Mrp2 protein determined by Western analysis of total liver homogenate decreased to 50% of control levels in pregnant rats, consistent with studies using plasma membranes. Confocal immunohistochemistry showed that Mrp2 expression was confined to the canalicular membrane in both control and pregnant rats and was not detectable in intracellular compartments. In isolated perfused liver, the biliary excretion of 2,4-dintrophenyl-glutathione was significantly decreased in pregnancy, consistent with decreased expression of Mrp2. The expression of the basolateral transporter Mrp1 was not altered in pregnancy, whereas expression of Mrp6 mRNA was decreased by 60%. Expression of Mrp3 was also decreased by 50% in pregnant rat liver, indicating differential regulation of Mrp isoforms in pregnancy. These data also demonstrate that decreased Mrp2 expression is not necessarily accompanied by increased Mrp3 expression.

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Preclinical Trial of Traditional Plant Remedies for the Treatment of Complications of Gestational Malaria

Medicines ◽

10.3390/medicines8120079 ◽

2021 ◽

Vol 8 (12) ◽

pp. 79

Author(s):

Peter Uchenna Amadi ◽

Emmanuel Nnabugwu Agomuo ◽

Chinyere Nneka Ukaga ◽

Uche Chinedu Njoku ◽

Joy Adaku Amadi ◽

...

Keyword(s):

Malaria In Pregnancy ◽

Herbal Remedies ◽

Therapeutic Effects ◽

Pregnant Rats ◽

Crown Rump Length ◽

Preclinical Trial ◽

Pregnant Rat ◽

Average Percentage ◽

Significant Difference ◽

In Pregnancy

Background: Most pregnant women living in high malaria endemic regions of Nigeria use herbal remedies for the management of malaria-in-pregnancy, rather than the commonly prescribed drugs. Remedies common to this area involve a suspension of A. indica (AI) leaves and in some cases, a suspension containing a mixture of AI and D.edulis (PS). Aim: This study examined the therapeutic efficacies of AI, PS, or a combination of AI and PS in a pregnant rat model for exoerythrocytic stages of Plasmodium falciparum parasite. Method: A predetermined sample size of 30 dams was used (for a power level and confidence interval of 95%), and divided equally into six groups made up of non-malarous dams, untreated malarous dams, and malarous dams either treated exclusively with 1 mL of 3000 mg/kg b.w AI, 1000 mg/kg b.w PS, AI + PS (50% v/v), or 25 mg/kg b.w CQ. Result: No maternal mortality was recorded. AI significantly improved maternal weight gain from 32.4 to 82.2 g and placental weight from 0.44 to 0.53 g. In the curative test, AI and AI + PS significantly reduced the average percentage parasitemia (APP) in the pregnant rats from >80% to <20%. No significant difference in the APP was found between the pregnant rats treated with any of CQ or AI during the suppressive test. Results for the prophylactic test of the study groups showed that the APP was significantly reduced from 24.69% to 3.90% when treated with AI and 3.67% when combined with PS. AI + PS reduced diastolic blood pressure from 89.0 to 81.0 mm/Hg and compared with that of the non malarous dams. AI or AI + PS significantly increased the platelet counts (103 µL) from 214.1 to 364.5 and 351.2, respectively. AI and AI + PS improved birth weight from 2.5 to 3.9 g and crown rump length from 2.6 to 4.1 cm. For biomarkers of preeclampsia, combining AI and PS led to the reversal of the altered levels of creatine kinase, lactate dehydrogenase, cardiac troponin, soluble Fms-Like Tyrosine Kinase-1, and placental growth factor. Conclusions: This study validates the use of A. indica for the treatment of gestational malaria due to its antiplasmodial and related therapeutic effects and in combination with pear seeds for the management of malaria-in-pregnancy-induced preeclampsia.

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Phycocyanin Decrease Trophoblast Il-17 Expression in Preeclamptic Rat Models

International Journal of Pharmaceutical and Clinical Research ◽

10.25258/ijpcr.v9i04.8543 ◽

2017 ◽

Vol 9 (04) ◽

Author(s):

Gondo H. K. ◽

Kusworini H. ◽

Arsana W. ◽

Sardjono W.

Keyword(s):

Body Weight ◽

Immune Functions ◽

Pregnant Rats ◽

Pregnant Rat ◽

Rat Models ◽

Blue Green Algae ◽

Tissue Invasion ◽

Lack Of Information ◽

Anti Inflammatory ◽

In Pregnancy

Preeclampsia/eclampsia (PEE) was the main cause of death in pregnancy. However, until now, this disease has no adequate medical prevention for lack of its basic molecular pathomechanism. In recent years, there are growing number of study has concern trophoblast apoptosis as important trigger. Thropoblast apoptosis has been shown in many report lead to trophoblast failure to invade into endometrial tissue. Invasion failure of trophoblast was characterized with high expression of IL-17 in its tissue. Spirulina arthrospira plant or also called blue-green algae has been consumed since by the Aztec tribe. Several studies have proven that this plant have the immunomodulation properties stimulate various immune functions such as production of cytokines, chemokines and other anti-inflammatory mediators. Its active bioactive Phycocyanin (PC) has been shown have an effect as anti-inflammatory and antioxidant. Previous study has been shown that this substance has beneficial effect in preeclampsia inhibition in rat models via its inflammatory reducing effect However, there are lack of information concerning its role in trophoblast IL-17. Hence, this study is conduct to reveal its role in IL-17 expression in trophoblast in preeclampsia. Methods. This research used animal models with PE/E pregnant rat. PE/E induced by IL-6 intravein at dose 5 ng/100 g/day body weight. Animals divided in 6 groups of treatment with two groups control and four groups of PC treatment in different dose. After decapitated, uterus tissue processed to view its IL-17 expression using immunofluoresnce Result. This study has proven IL-17 reducing effect of PC in preeclampsia model of pregnant rats induced by IL -6. PC has reducing IL-17 expression significantly in trophoblast tissue of pregnant rats models induced by IL-6 at dose of 40 ng/100 kg weight. Conclusion. This study confirm that PC has a protective effect on pregnant rats preeclampsia through its inhibiton of trophoblast IL-17.

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Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention

AJP Renal Physiology ◽

10.1152/ajprenal.00147.2015 ◽

2015 ◽

Vol 309 (1) ◽

pp. F63-F70 ◽

Cited By ~ 6

Author(s):

Crystal A. West ◽

Alicia A. McDonough ◽

Shyama M. E. Masilamani ◽

Jill W. Verlander ◽

Chris Baylis

Keyword(s):

Mrna Expression ◽

Regional Differences ◽

Late Pregnancy ◽

Kidney Cortex ◽

Apical Region ◽

Plasma Volume Expansion ◽

Pregnant Rats ◽

Pregnant Rat ◽

Apical Localization ◽

In Pregnancy

Pregnancy is characterized by plasma volume expansion due to Na+ retention, driven by aldosterone. The aldosterone-responsive epithelial Na+ channel is activated in the kidney in pregnancy. In the present study, we investigated the aldosterone-responsive Na+-Cl− cotransporter (NCC) in mid- and late pregnant rats compared with virgin rats. We determined the abundance of total NCC, phosphorylated NCC (pNCC; pT53, pS71 and pS89), phosphorylated STE20/SPS-1-related proline-alanine-rich protein kinase (pSPAK; pS373), and phosphorylated oxidative stress-related kinase (pOSR1; pS325) in the kidney cortex. We also measured mRNA expression of NCC and members of the SPAK/NCC regulatory kinase network, serum and glucocorticoid-regulated kinase (SGK)1, total with no lysine kinase (WNK)1, WNK3, and WNK4. Additionally, we performed immunohistochemistry for NCC kidneys from virgin and pregnant rats. Total NCC, pNCC, and pSPAK/OSR1 abundance were unchanged in midpregnant versus virgin rats. In late pregnant versus virgin rats, total NCC and pNCC were decreased; however, pSPAK/OSR1 was unchanged. We detected no differences in mRNA expression of NCC, SGK1, total WNK1, WNK3, and WNK4. By immunohistochemistry, NCC was mainly localized to the apical region in virgin rats, and density in the apical region was reduced in late pregnancy. Therefore, despite high circulating aldosterone levels in pregnancy, the aldosterone-responsive transporter NCC is not increased in total or activated (phosphorylated) abundance or in apical localization in midpregnant rats, and all are reduced in late pregnancy. This contrasts to the mineralocorticoid-mediated activation of the epithelial Na+ channel, which we have previously reported. Why and how NCC escapes aldosterone activation in pregnancy is not clear but may relate to regional differences in aldosterone sensitivity the increased K+ intake or other undefined mechanisms.

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EFFECTS OF PREGNANCY IN THE RAT ON THE SIZE AND INSULIN SECRETORY RESPONSE OF THE ISLETS OF LANGERHANS

Journal of Endocrinology ◽

10.1677/joe.0.0540317 ◽

1972 ◽

Vol 54 (2) ◽

pp. 317-325 ◽

Cited By ~ 87

Author(s):

I. C. GREEN ◽

K. W. TAYLOR

Keyword(s):

Islets Of Langerhans ◽

Fasting Blood Glucose ◽

Insulin Response ◽

Secretory Response ◽

Pregnant Rats ◽

Adenyl Cyclase Activity ◽

Pregnant Rat ◽

Rat Islets ◽

Increased Sensitivity ◽

In Pregnancy

SUMMARY The secretory response of rat islets of Langerhans was examined during pregnancy and compared with insulin release in normal rat islets. The threshold for a secretory response to glucose was lowered for islets from pregnant rats by comparison with non-pregnant controls. In addition, such islets showed a greatly increased sensitivity to glucose concentrations over the range 3·5–20 mmol/1. Significantly lower fasting blood glucose levels were found in pregnant rats in vivo, compared with controls. Insulin secretagogues other than glucose were tested for their effects on islets during pregnancy. Despite the high baseline of insulin secretion in response to glucose in pregnancy, there was an additional increased secretory response to arginine and theophylline. In contrast to their response to glucose, pregnant rat islets did not display an increased sensitivity to leucine. Glucagon, while it increased the insulin response of normal islets, had no significant effect on increasing the insulin response from pregnant rat islets suggesting that adenyl cyclase activity is already highly stimulated in pregnancy. In addition, the insulin, DNA and protein content of islets during pregnancy were increased significantly above normal values. The results suggested that rat islets are not only larger in pregnancy, but that they possess a more sensitive mechanism for detecting and responding to glucose and other secretagogues.

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Tubuloglomerular feedback activity in virgin and 12-day-pregnant rats

AJP Renal Physiology ◽

10.1152/ajprenal.1985.249.1.f169 ◽

1985 ◽

Vol 249 (1) ◽

pp. F169-F173 ◽

Cited By ~ 4

Author(s):

C. Baylis ◽

R. C. Blantz

Keyword(s):

Plasma Volume ◽

Filtration Rate ◽

Distal Tubule ◽

Feedback System ◽

Proximal Tubules ◽

Tubuloglomerular Feedback ◽

Pregnant Rats ◽

Pregnant Rat ◽

The Difference ◽

In Pregnancy

Tubuloglomerular feedback activity was evaluated by micropuncture and microperfusion techniques in virgin and 12-day-pregnant Munich-Wistar rats. Plasma volume increases in pregnancy, which could suppress feedback activity, thus contributing to the rise in glomerular filtration rate observed in normal midterm pregnancy. Late proximal tubules were microperfused at 0, 10, 20, and 40 nl/min and the resulting filtration rate in the same nephron was evaluated. Nephron filtration rate (SNGFR) in proximal and distal tubules of other nephrons was also measured to assess the degree of activation of the tubuloglomerular feedback system and the relation of the spontaneous (normal) late proximal flow rate and SNGFR (distal tubule collections). SNGFR decreased significantly (from the 0 nl/min perfusion value) when late proximal tubules were perfused at 20 and 40 nl/min in both virgin and 12-day-pregnant rats. Tubuloglomerular feedback activity was not suppressed in pregnancy, but the relationship between SNGFR and late proximal tubule perfusion rate was reset for a higher value for SNGFR. The difference between proximal and distal SNGFR suggests that the feedback system was more activated in the virgin than in the pregnant rat. Thus, in spite of the known increases in plasma volume that occur in pregnancy, the kidney does not sense this volume expansion as a stimulus to suppress feedback activity.

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Up-regulation of oxytocin receptors in non-pregnant rat myometrium by isoproterenol: effects of steroids

Journal of Endocrinology ◽

10.1677/joe.0.1610403 ◽

1999 ◽

Vol 161 (3) ◽

pp. 403-411 ◽

Cited By ~ 16

Author(s):

T Engstrom ◽

P Bratholm ◽

NJ Christensen ◽

H Vilhardt

Keyword(s):

Gene Expression ◽

Plasma Membranes ◽

Contractile Response ◽

Oxytocin Receptor ◽

Gonadal Steroids ◽

Pregnant Rats ◽

Pregnant Rat ◽

Oxytocin Receptors ◽

Important Regulator ◽

Isoproterenol Infusion

The objective of the present study was to further elucidate our previous observation that beta2-adrenoceptor activation induces oxytocin receptor (OTR) expression in rat myometrium. We wanted to investigate whether the mechanism behind this effect was under the influence of gonadal steroids. Ovariectomized non-pregnant rats were treated with estrogen, progesterone or a combination of both for 3 days. Some rats were concomitantly treated with isoproterenol. Estrogen treatment increased both OTR mRNA production and maximal binding of [3H]-oxytocin to isolated myometrial plasma membranes, but it did not affect contractility of isolated uterine strips challenged with oxytocin. When the estrogen regimen was combined with isoproterenol treatment, an augmented maximal contractile response (Emax) to oxytocin was observed although no further increase in OTR mRNA and binding was seen. Progesterone treatment did not in itself alter OTR mRNA, OTR binding or Emax. However, OTRs were induced at the level of gene expression when progesterone was supplemented with isoproterenol infusion. Finally, progesterone suppressed the effect of estrogen on OTR mRNA production and binding when the two compounds were administered together. However, when isoproterenol treatment was added this effect was abolished and Emax was enhanced more than that seen following treatment with estrogen alone. These data suggest that beta2-adrenoceptor activation represents an important regulator of OTR expression/function in estrogen- and progesterone-dominated rat myometrium.

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Nutrition in pregnancy: testing the effects of the diet of the poorest socioeconomic group in Scotland on the liver of pregnant rats

10.26226/morressier.5ef37080b2a27f760262bb4f ◽

2020 ◽

Author(s):

William David Rees ◽

Halil Dasgin

Keyword(s):

Socioeconomic Group ◽

Pregnant Rats ◽

Pregnancy Testing ◽

In Pregnancy

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Tenofovir and Severe Symptomatic Hypophosphatemia

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709619848796 ◽

2019 ◽

Vol 7 ◽

pp. 232470961984879 ◽

Cited By ~ 2

Author(s):

Asim Kichloo ◽

Savneek Singh Chugh ◽

Sanjeev Gupta ◽

Jay Panday ◽

Ghazaleh Goldar

Keyword(s):

Renal Damage ◽

Organic Anion ◽

Significant Risk ◽

Anion Transporters ◽

Immunodeficiency Virus ◽

Tubular Lumen ◽

Associated Proteins ◽

Proximal Tubular ◽

Renal Tubular ◽

Initial Results

Tenofovir is a broadly used drug used for the treatment of human immunodeficiency virus (HIV). Although the initial results of the clinical trials supported the renal safety of Tenofovir, clinical use of it has caused a low, albeit a significant, risk of renal damage either in the form of AKI or CKD. The pathophysiology has been linked to the effect of this medication on the proximal tubular cell. Although the exact mechanism is unknown, studies have suggested that Tenofovir accumulates in proximal tubular cells which are rich in mitochondria. It is both filtered in the glomerulus and actively secreted in the tubules for elimination and is excreted unchanged in the urine. Studies have shown an active transportation of 20-30% of this drug into the renal proximal tubule (PCT) cells via the organic anion transporters in the baso-lateral membrane (primarily hOAT1, and OAT3 to a lesser extent) and ultimate excretion of the drug into the tubular lumen via the transporters in the proximal tubular apical membrane MRP4 and MRP2 (multidrug resistance-associated proteins 2 & 4). Subsequently, the mitochondrial injury caused by Tenofovir can lead to the development of Fanconi’s syndrome which causes renal tubular acidosis, phosphaturia, aminoaciduria, glucosuria with normoglycemia, and tubular proteinuria. Here we present a case where Tenofovir treatment resulted in severe hypophosphatemia requiring hospitalization for parentral phosphate repletion.

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