Tocotrienol in Pre-Eclampsia Prevention: A Mechanistic Analysis in Relation to the Pathophysiological Framework

Abstract

The pathophysiology of pre-eclampsia involves two major pathways, namely systemic oxidative stress and subsequent generalised inflammatory response, which eventually culminates in endothelial cell injury and the syndrome of pre-eclampsia with multi-organ dysfunction. Aspirin has been used to reduce the risk of pre-eclampsia, but it only possesses anti-inflammatory properties without any antioxidant effect. Hence, it can only partially alleviate the problem. Tocotrienols are a unique form of vitamin E with strong antioxidant and anti-inflammatory properties that can be exploited as a preventive agent for pre-eclampsia. Many preclinical models showed that tocotrienol can also prevent hypertension and ischaemic/reperfusion injury, which are the two main features in pre-eclampsia. This review explores the mechanism of action of tocotrienol in relation to the pathophysiology of pre-eclampsia. In conclusion, the study provides sufficient justification for the establishment of a large clinical trial to thoroughly assess the capability of tocotrienol in preventing pre-eclampsia.

Keywords: anti-inflammation; antioxidant; hypertension; ischaemia; vitamin E.

Figure 1

Pre-eclampsia begins with defective placental implantation, which leads to recurrent ischaemia and reperfusion cycles that result in oxidative and inflammatory damages to the tissue. Damage-associated molecules cause systemic endothelial dysfunction and various features of pre-eclampsia. Abbreviations: Ab, antibody; AT-1, angiotensin-1; ET-1, endothelin-1; NO, nitric oxide; sFlt-1, soluble fms-like tyrosine kinase 1.

Figure 2

Molecular structures of tocopherols and tocotrienols. They consist of a chromanol ring and a long carbon tail. Tocopherols and tocotrienols have saturated and unsaturated carbon tails, respectively. Each isomer is distinct from each other by the position of the methyl side chain on the chromanol ring. The structures were obtained from PubChem.

Figure 3

Theoretical framework of how tocotrienol prevents pre-eclampsia. Tocotrienol exerts anti-inflammatory and antioxidant actions, which prevent the oxidative and inflammatory damages caused by ischaemia. The same properties also prevent hypertension in pre-eclampsia. Abbreviation: Ab, antibody; AT-1, angiotensin-1; ET-1, endothelin-1; NF-κB, nuclear factor kappa-B; NO, nitric oxide; NRF2; nuclear factor erythroid 2-related factor 2; T3, tocotrienol; sFlt-1, soluble fms-like tyrosine kinase 1.