Role of Nifedipine, Nicorandil, and Coenzyme Q10 Supplementation in The Treatment of Patients with Severe Preeclampsia: A Single Blinded Randomized Controlled Trial
Maged Mishel Matta1, Tarek Abdel-Zaher Karkor2, Tamer Mamdouh Abdel-Dayem2, Gehad Mahmoud Khamis1 and Eman Ibrahim Anwar1*
1Clinical Pharmacology, Faculty of Medicine, University of Alexandria, Egypt
12Obstetrics and Gynecology, Faculty of Medicine, University of Alexandria, Egypt
*Corresponding Author: Eman Ibrahim Anwar, Lecturer in Clinical Pharmacology, Faculty of Medicine, University of Alexandria, Egypt.
November 15, 2021 Published: December 30, 2021
The study was designed to evaluate the effect of nifedipine and nicorandil, used either alone or combined with coenzyme Q10 supplementation, on preeclampsia. It is a single blinded randomized controlled trial conducted on 140 patients diagnosed as severe pre-eclampsia. They were randomly assigned to four groups: Group (I) who received nifedipine, group (II) who received nicorandil, group (III) who received nifedipine + coenzyme Q10 an group (IV) who received nicorandil + coenzyme Q10. Patients were assessed before and 48 hours after drugs administration. Nifedipine and nicorandil showed significant decrease in arterial blood pressure and improvement in Doppler parameters. Moreover, both nifedipine and nicorandil significantly increased endothelial nitric oxide synthase activity and superoxide dismutase activity and decreased malondialdehyde level and platelets aggregation, with no significant difference between them. The improvement in Doppler ultrasound parameters by nifedipine and nicorandil was significantly augmented by addition of coenzyme Q10 to both drugs. Coenzyme Q10 supplementation also showed a more significant increase in the superoxide dismutase activity with a more significant decrease in the malondialdehyde level. In conclusion, Coenzyme Q10, combined with either nifedipine or nicorandil might have beneficial effects on preeclampsia by lowering the oxidative stress induced vascular remodeling.
Keywords: Preeclampsia; Nifedipine; Nicorandil; Coenzyme Q10; Oxidative Stress; Vascular Remodeling
- Armaly Z., et al. “Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches”. Frontiers in Physiology 9 (2018): 973.
- Jim B and Karumanchi SA. “Preeclampsia: Pathogenesis, Prevention, and Long-Term Complications”. Seminar on Nephrology4 (2017): 386-397.
- Serdar Z., et al. “Lipid and protein oxidation and antioxidant function in women with mild and preeclampsia”. Archives of Gynecology and Obstetrics 1 (2003): 19-25.
- Kulandavelu S., et al. “Endothelial nitric oxide synthase deficiency reduces uterine blood flow, spiral artery elongation, and placental oxygenation in pregnant mice”. Hypertension1 (2012): 231-238.
- Firoz T., et al. “Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review”. BJOG10 (2014): 1210-1218; discussion 20.
- Yilmaz Osman and Göncü Ayhan Şule. "Effects of nifedipine on fetal cardiac function in preterm labor" Journal of Perinatal Medicine7 (2020): 723-727.
- Bentinger M., et al. “Coenzyme Q--biosynthesis and functions”. Biochemical and Biophysical Research Communications 1 (2010): 74-79.
- Teran E., et al. “Preeclampsia is associated with a decrease in plasma coenzyme Q10 levels”. Free Radical Biology and Medicine 11 (2003): 1453-1456.
- Hayashi T., et al. “eNOS-dependent antisenscence effect of a calcium channel blocker in human endothelial cells”. PLoS One2 (2014): e88391.
- Ding Y and Vaziri ND. “Nifedipine and diltiazem but not verapamil up-regulate endothelial nitric-oxide synthase expression”. Journal of Pharmacology and Experimental Therapeutics 2 (2000): 606-609.
- Loiola RA., et al. “Role of vascular Kinin B1 and B2 receptors in endothelial nitric oxide metabolism”. Peptides 8 (2011): 1700-1705.
- S KSS., et al. “Nifedipine inhibits hypoxia induced transvascular leakage through down regulation of NFkB”. Respiratory Physiology and Neurobiology 1 (2012): 26-34.
- Sugiura T., et al. “Nifedipine improves endothelial function: role of endothelial progenitor cells”. Hypertension3 (2008): 491-498.
- Young HY., et al. “Synergistic effect of ginger and nifedipine on human platelet aggregation: a study in hypertensive patients and normal volunteers”. American Journal of Chinese Medicine 4 (2006): 545-551.
- Chou TC. “New mechanisms of antiplatelet activity of nifedipine, an L-type calcium channel blocker”. Biomedicine (Taipei) 4 (2014): 24.
- Tajima M., et al. “Nicorandil enhances the effect of endothelial nitric oxide under hypoxia-reoxygenation: role of the KATP channel’. European Journal of Pharmacology1-3 (2008): 86-92.
- Horinaka S., et al. “Nicorandil but not ISDN upregulates endothelial nitric oxide synthase expression, preventing left ventricular remodeling and degradation of cardiac function in Dahl salt-sensitive hypertensive rats with congestive heart failure”. Journal of Cardiovascular Pharmacology 5 (2006): 629-635.
- Pang Z., et al. “Cardioprotective Effects of Nicorandil on Coronary Heart Disease Patients Undergoing Elective Percutaneous Coronary Intervention”. Medical Science Monitor 23 (2017): 2924-2930.
- Cheng K., et al. “The Role of Nicorandil in the Management of Chronic Coronary Syndromes in the Gulf Region”. Advances in Therapy2 (2021): 925-948.
- “Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial”. Lancet9314 (2002): 1269-1275.
- Yadav R., et al. “Acute hemodynamic effects of nicorandil in patients with primary pulmonary arterial hypertension”. Indian Heart Journal6 (2005): 666-669.
- Kool MJ., et al. “Acute and subacute effects of nicorandil and isosorbide dinitrate on vessel wall properties of large arteries and hemodynamics in healthy volunteers”. Cardiovascular Drugs and Therapy 2 (1995): 331-337.
- Liu HT., et al. “Effects of coenzyme Q10 supplementation on antioxidant capacity and inflammation in hepatocellular carcinoma patients after surgery: a randomized, placebo-controlled trial”. Nutrition Journal 1 (2016): 85.
- Song MH., et al. “Effects of coenzyme Q10 on the antioxidant system in SD rats exposed to lipopolysaccharide-induced toxicity”. Laboratory Animal Research1 (2017): 24-31.
- Littarru GP and Tiano L. “Bioenergetic and antioxidant properties of coenzyme Q10: recent developments”. Molecular Biotechnology1 (2007): 31-37.
- Pacher P., et al. “Nitric oxide and peroxynitrite in health and disease”. Physiology Review1 (2007): 315-424.
- Pepe S., et al. “Coenzyme Q10 in cardiovascular disease”. Mitochondrion 7 (2007): S154-167.
- Gao L., et al. “Effects of coenzyme Q10 on vascular endothelial function in humans: a meta-analysis of randomized controlled trials”. Atherosclerosis2 (2012): 311-316.
- Fenakel K., et al. “Nifedipine in the treatment of preeclampsia”. Obstetrics and Gynecology3 (1991): 331-337.
- Liu QQ., et al. “Clinical efficacy and perinatal outcome of nifedipine for preeclampsia: meta-analysis”. Zhonghua Fu Chan Ke Za Zhi8 (2012): 592-597.
- Paul Guerby., et al. “Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia”. Redox Biology 40 (2020): 101861.
- Lokeswara Angga Wiratama., et al. “Preeclampsia: From Cellular Wellness to Inappropriate Cell Death, and the Roles of Nutrition”. Frontiers in Cell and Developmental Biology 9 (2021): 30-31.
- Martin T Johnson., et al. “L-type Ca2+ channel blockers promote vascular remodeling through activation of STIM proteins”. Proceedings of the National Academy of Sciences29 (2020): 17369-17380.
- Tolcher MC., et al. “Intravenous labetalol versus oral nifedipine for acute hypertension in pregnancy: effects on cerebral perfusion pressure”. American Journal of Obstetrics and Gynecology 3 (2020): 441.e1-441.e8.
- Xiaosi Jiang., et al. “Protective Effect of Nicorandil on Cardiac Microvascular Injury: Role of Mitochondrial Integrity". Oxidative Medicine and Cellular Longevity (2021): 10.
- Massimiani M., et al. “Treatment of pregnancies complicated by intrauterine growth restriction with nitric oxide donors increases placental expression of Epidermal Growth Factor-Like Domain 7 and improves fetal growth: A pilot study”. Translation Research 228 (2021): 28-41.
- Gutierrez-Mariscal Francisco M., et al. “Coenzyme Q10 and Cardiovascular Diseases”. Antioxidants (Basel, Switzerland)6 (2021): 906.