Phycocyanin Decrease Trophoblast Il-17 Expression in Preeclamptic Rat Models

Author(s):  
Gondo H. K. ◽  
Kusworini H. ◽  
Arsana W. ◽  
Sardjono W.

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.

Author(s):  
INARAH FAJRIATY ◽  
HAFRIZAL RIZA ◽  
FAJAR NUGRAHA ◽  
FRENGKI FRIANTO

Objectives: Drugs can cause undesired effects on the fetus during pregnancy, especially embryonic/organogenesis which could lead to defects in the fetus because some types of drugs can penetrate the placenta and will undergo biotransformation into a highly reactive compound that has the potential to become a teratogenic compound. The aim of this research was to examine the teratogenic effect of bintangur leaves (Calophyllum soulattri Burm. F) ethanol extract to Sprague Dawley strain white rats. Methods: The white rats are divided into four treatment groups: Control group was given carboxymethyl cellulose Na 1%, comparison group was given trimethoprim 360 mg/kg BW, C. soulattri leaves ethanol extract (CLE) 100 mg/kg BW, and CLE 500 mg/kg BW. The treatment was administrated since organogenesis period. Cesarian section was performed to pregnant rat at the 20th day to separate the fetuses. Observation covered body weight of pregnant rats, fetal biometric, morphological malformation, and skeletal formation. Results: CLE 100 mg/kg BW and 500 mg/kg BW did not cause any change in the number of a living fetus, body weight, and length of fetuses like the comparison group. Both doses of CLE shown have a normal skeletal formation. Resorption was found in the comparison group and CLE 100 mg/kg BW with the percentage was 65.21% and 6.67%. It was found that there is no significant difference (p<0.05) between both doses of CLE compared to control group. Conclusion: From the results, it is concluded that CLE did not have the teratogenic effect.


1998 ◽  
Vol 9 (1) ◽  
pp. 9-13
Author(s):  
E Podjarny ◽  
J Bernheim ◽  
B Katz ◽  
J Green ◽  
J Mekler ◽  
...  

Insulin resistance and hyperinsulinemia are associated with essential hypertension. There is also evidence of hyperinsulinemia in women who developed hypertension in pregnancy (P). The present study examines whether chronic hyperinsulinemia in pregnant rats plays a role in the development of hypertension in pregnancy. A sustained-release insulin pellet was implanted subcutaneously in 15 Wistar rats (P-INS) 1 wk before and on day 7 of pregnancy; 14 control rats were sham-implanted (P-SHAM). Tail-cuff systolic BP (SBP), serum triglycerides, glucose, insulin, renal function, and urinary excretion of Na+ and of metabolites of nitric oxide were determined throughout pregnancy. Data were analyzed by ANOVA with basal body weight as covariate analysis of covariance. Results are expressed as the mean +/- SD. Body weight; water and food intake; urine volume; creatinine clearance; and level of proteinuria at the end of pregnancy were similar in both groups. The number of fetuses was 9 +/- 2.3 in P-INS versus 11 +/- 2.4 in pregnant control rats (P < 0.05). Before mating, SBP was similar, but at the end of pregnancy SBP was 110 +/- 18 mmHg in P-INS versus 85 +/- 12 mmHg in pregnant rats (P < 0.05). Serum triglycerides and Na+ were also higher in P-INS rats. The fractional excretion of Na+ was 3.1 +/- 1.0 versus 4.4 +/- 1.5, respectively (P < 0.01). The percent increase in nitric oxide metabolite excretion was 233 +/- 14 versus 370 +/- 17%, respectively (P < 0.01). Chronic hyperinsulinemia, without sugar supplementation, and hypertriglyceridemia may cause a decrease in the synthesis of nitric oxide in P-INS rats. The development of hypertension in these rats may be associated with an impaired vasodilatation, together with an increased renal sodium reabsorption.


Author(s):  
Hery Wijayanto ◽  
Tri Wahyu Pangestiningsih ◽  
Erdiansyah Rahmi

The study was conducted to investigate the effects of caffeine treatment during organogenesis period to the fetal birth weight, using rat (Rattus norvegicus) as the animal model. Thirty-six primipararat obtained from Unit Pengembangan Hewan Percobaan, Gadjah Mada University (UPHP-GMU), 3 month old, 165-200 g body weight, were divided into 6 groups, consisted of 6 rats each. Six of the ratshave been selected based on the estrous cycles, and only rat with regular estrous were use for theexperiment. The rat then were mated, and during day 6-14 of the pregnancies were treated orally withcaffeine diluted in aquadest in dosage: placebo (1 cc aquadest) for group I (control), and 5.4, 10.8, 16.2,21.6, and 27 g/200 g body weight/day for treatment groups II-VI respectively. The pregnant rat bodyweights were determined at day 6 of pregnancies for calculating the caffeine treatment dosages. At day 20thof the pregnancies all of the pregnant rats were caesarotomized, and all of the fetuses were removed and weighed. The results showed that all of the treatment groups have significantly lower birth weightcompare to the groups control group. More over, fetal obtained from the treatment groups also showedserious subcutaneous hemorrhagic.Keywords: organogenesis, Rattus norvegicus, birth weight


2002 ◽  
Vol 283 (3) ◽  
pp. G757-G766 ◽  
Author(s):  
Jingsong Cao ◽  
Bruno Stieger ◽  
Peter J. Meier ◽  
Mary Vore

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.


Medicines ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 79
Author(s):  
Peter Uchenna Amadi ◽  
Emmanuel Nnabugwu Agomuo ◽  
Chinyere Nneka Ukaga ◽  
Uche Chinedu Njoku ◽  
Joy Adaku Amadi ◽  
...  

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.


2015 ◽  
Vol 309 (1) ◽  
pp. F63-F70 ◽  
Author(s):  
Crystal A. West ◽  
Alicia A. McDonough ◽  
Shyama M. E. Masilamani ◽  
Jill W. Verlander ◽  
Chris Baylis

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.


2001 ◽  
Vol 100 (6) ◽  
pp. 667-671 ◽  
Author(s):  
Eduardo PODJARNY ◽  
Michael BURSZTYN ◽  
Gloria RASHED ◽  
Sidney BENCHETRIT ◽  
Bernard KATZ ◽  
...  

Recent studies have shown that maternal hyperinsulinaemia is a risk factor for the development of hypertension in pregnancy. Experimentally, pregnant rats with chronic exogenously induced hyperinsulinaemia (P-INS rats) have increased blood pressure at the end of gestation. This is associated with a blunted elevation of the excretion of the urinary metabolites of nitrate (UNOx). In the present study, we aimed to evaluate the mechanism(s) of the increase in blood pressure in this model. Four groups were studied: normal pregnant rats (P rats), P-INS rats, P-INS rats treated with l-arginine (2 g/l in the drinking water) (l-ARG rats) and hyperinsulinaemic virgin rats (V-INS rats). Systolic blood pressure (SBP), UNOx excretion (on ingestion of a controlled low-nitrate diet), urine noradrenaline (norepinephrine) and plasma endothelin levels were evaluated. Rats were killed on day 22 of pregnancy. Five P-INS rats were not killed at this time, in order to measure SBP 30 and 60 days after delivery. Fetal number and fetal body weight were evaluated. At the end of pregnancy, a 10±3% increase in SBP was found in P-INS rats, contrasting with a fall of -15±4% in P rats (P < 0.01). In the l-ARG group at the end of pregnancy, SBP values had fallen by -14±2%, to values comparable with those of P rats. The increase in UNOx excretion was 175±38% in P rats, 106±12% in l-ARG rats and 41±8% in P-INS rats (P < 0.01 compared with P and l-ARG groups). No differences were found in the urinary excretion of noradrenaline or in the plasma levels of endothelin-1 between the pregnant groups. Fetal number was similar in all groups, but fetal body weight was lower for P-INS rats compared with P and l-ARG rats. Thus the blood pressure response to l-arginine strongly suggests that a decrease in NO availability may be the main pathogenic mechanism involved in the development of hypertension in this model.


1972 ◽  
Vol 54 (2) ◽  
pp. 317-325 ◽  
Author(s):  
I. C. GREEN ◽  
K. W. TAYLOR

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.


2014 ◽  
Vol 306 (11) ◽  
pp. R796-R803 ◽  
Author(s):  
Tracey L. Weissgerber ◽  
Andrea McConico ◽  
Bruce E. Knudsen ◽  
Kim A. Butters ◽  
Suzanne R. Hayman ◽  
...  

Free vascular endothelial growth factor (VEGF) is undetectable in plasma during human pregnancy. However, studies examining pregnant rats have reported both low (8–29 pg/ml) and high (527–1,030 pg/ml) free VEGF. These discrepancies cast uncertainty over the use of rat models to study angiogenic factors in pregnancy and preeclampsia. This study investigates methodological factors that may explain these discrepancies. Plasma VEGF in nonpregnant, day 7 pregnant, and day 19 pregnant rats was measured using rat and mouse ELISAs (R&D Systems). The rat ELISA detected VEGF in plasma from nonpregnant rats but not in plasma from day 19 pregnant rats. The mouse ELISA detected higher VEGF concentrations than the rat ELISA in every sample tested. This discrepancy was greater in day 19 pregnant rats (median: 2,273 vs. 0 pg/ml) than in nonpregnant (97 vs. 20 pg/ml) and day 7 pregnant (66 vs. 2 pg/ml) rats. Recovery of recombinant rat VEGF (rrVEGF) spiked into plasma from nonpregnant and day 7 pregnant rats was high for the rat ELISA (82–105%) but low for the mouse ELISA (17–22%). The rat ELISA did not recover rrVEGF in plasma from day 19 pregnant rats, suggesting that this ELISA measures free VEGF. The use of the rat versus mouse ELISA likely explains the differences in reported VEGF concentrations in pregnant rats. While the rat ELISA appears to measure free VEGF, plasma concentrations in nonpregnant and pregnant rats are below the assay sensitivity limit. As most previous studies of pregnant rats used the mouse VEGF ELISA, these data should be interpreted cautiously.


1985 ◽  
Vol 249 (1) ◽  
pp. F169-F173 ◽  
Author(s):  
C. Baylis ◽  
R. C. Blantz

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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