Effect of curcumin on inflammatory and oxidative stress markers in Lipopolysaccharide induced animal models of pre-eclampsia

Abstract

Introduction: A substantial percentage of fetal, maternal, and neonatal morbidity and mortality is traced to Pre-eclampsia, a life threatening disease. Typical symptoms of the disease include de novo hypertension, proteinuria, renal failure, neurological problems, elevated liver enzymes, and uteroplacental dysfunction. It is estimated that almost 8-10% of all pregnancies are affected by preeclampsia in India. Pre-eclampsia incidentally also involves immune system changes on similar lines as a typical pregnancy. Immune cells like CD4+ T-helper 1 (TH1) cells, cytotoxic NK cells, and autoreactive B cells secrete substances that cause an increase in innate immune activation and inflammation in the maternal circulation and uteroplacental unit, instead of immune changes that promote tolerance and inhibit reactivity to the fetus and placenta. Placental and systemic oxidative stress are the key factors in the emergence of preeclampsia. A number of physiological changes, mineral shortages, and increased oxygen use during pregnancy can all be considered potential causes of oxidative stress. There is yet no effective and secure pharmaceutical treatment for preeclampsia. Pregnancy related safety concerns and the complex aetiology are two significant barriers to the development of pre-eclampsia medications. Medicinal plants and derived products have long been recognized as valuable assets in the treatment of a variety of diseases. Curcumin is a naturally occurring substance with significant in vitro therapeutic promise. The objective of this study was to develop LPS (lipopolysaccharide) induced animal model of Pre-eclampsia and to estimate and compare the hemodynamic parameters, inflammatory markers, oxidative stress markers and proteinuria in pregnant control, LPS-induced Pre-eclampsia, and curcumin-treated Pre-eclampsia in experimental rats. Material and methods: Pre-eclampsia was induced by single dose of 0.5μg/kg LPS. Wistar rats were divided into 8 groups of 8 animals. Female wistar rats were placed with male rats overnight and examined the next morning for the presence of sperm in vaginal smears. The day on which sperm was detected was designated as gestational day 0. After confirmation of pregnancy, each rat was weighed and randomized into groups. Pregnant Wistar rats were given 0.5 μg /kg of body weight LPS intraperitoneally on gestational day 5 for developing Pre-eclampsia models. Protein estimation in urine was done after 24 hours. On 19th or 20th gestation day animals were anesthetized and blood pressure was measured through a non-invasive tail-cuff method using the AD instrument and also through invasive method by inserting a arterial catheter in either of the carotid arteries towards the heart. ECG recording was done through surface ECG recording. Blood was collected by cardiac puncture, centrifuged, and stored at -80ºC on 19th or 20th gestation day. Inflammatory markers were estimated through ELISA reader. Oxidative stress markers were estimated. Pregnancy outcome was assessed through placental weight, number of pup’s delivered and pup’s weight. Statistical analysis was done using one way analysis of variance (ANOVA) followed by post hoc Tukey‘s test for intergroup comparisons. Results: In LPS induced model of pre-eclampsia, single-dose treatment with LPS (0.5ug/kg) induced marked pre-eclampsia in rats. Treatment with curcumin significantly decreased the level of proteinuria, hemodynamic parameters, inflammatory markers and oxidative stress markers in pregnant LPS+ curcumin-treated group when compared with the pregnant LPS group. Treatment with curcumin significantly increases pup’s weight and number of pups. Conclusion: On the basis of this experimental study, it is proposed that curcumin appears to be a potential therapeutic agent as measured by effect on hemodynamic changes, proteinuria, inflammatory markers, oxidative stress markers and pregnancy outcomes in LPS-induced pre- eclampsia. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.