Endocrine disrupting chemicals (EDCs) are xenobiotics which adversely modify the hormone system. The endocrine system is most vulnerable to assaults by endocrine disruptors during the prenatal and early development window, and effects may persist into adulthood and across generations. The prenatal stage is a period of vulnerability to environmental chemicals because the epigenome is usually reprogrammed during this period. Bisphenol A (BPA), lead (Pb), and dichlorodiphenyltrichloroethane (DDT) were chosen for critical review because they have become serious public health concerns globally, especially in Africa where they are widely used without any regulation. In this review, we introduce EDCs and describe the various modes of action of EDCs and the importance of the prenatal and developmental windows to EDC exposure. We give a brief overview of epigenetics and describe the various epigenetic mechanisms: DNA methylation, histone modifications and non-coding RNAs, and how each of them affects gene expression. We then summarize findings from previous studies on the effects of prenatal exposure to the endocrine disruptors BPA, Pb and DDT on each of the previously described epigenetic mechanisms. We also discuss how the epigenetic alterations caused by these EDCs may be related to disease processes.

This study investigated the potential of stevioside to prevent oxidative DNA damage in the liver and kidney of type 2 diabetes mellitus (T2DM) using high fat-low streptozocin rat model. Rats were treated daily with 12.5, 25 and 50 mg/kg stevioside orally for 21 days. Levels of biomarkers of T2DM, lipid profile and oxidative stress were assayed spectrophotometrically. The DNA ladder assay method was used to assess DNA fragmentation in the liver and kidney while computational analysis was used to predict the mechanisms of antidiabetic properties of stevioside. Stevioside significantly (p < 0.05) decreased the levels of plasma glucose, insulin, dipeptidyl peptidase IV and activities of kidney angiotensin converting enzyme. Stevioside significantly reduced oxidative stress by decreasing the levels of lipid peroxidation and nitric oxide in the liver and kidney; thereby, reducing the extent of DNA fragmentation in the liver and kidney of the diabetic rats. The in silico analysis showed that the ability of stevioside to exert these effects is linked to its inhibition of beta-adrenergic receptor kinase and G-protein-coupled receptor kinase. The results of this study suggest that the prevention of DNA fragmentation may be an additional benefit of the use of stevioside in the management of T2DM.

Aflatoxins are toxic compounds produced by molds of the Aspergillus species that contaminate food primarily in tropical countries. The most toxic aflatoxin, aflatoxin B1 (AFB1), is a major cause of hepatocellular carcinoma (HCC) in these countries. In sub-Saharan Africa, aflatoxin contamination is common, and perinatal AFB1 exposure has been linked to the early onset of HCC. Epigenetic programming, including changes to DNA methylation, is one mechanism by which early life exposures can lead to adult disease. This study aims to elucidate whether perinatal AFB1 exposure alters markers of offspring health including weight, lipid, and hormone profiles as well as epigenetic regulation that may later influence cancer risk. Pregnant rats were exposed to two doses of AFB1 (low 0.5 and high 5 mg/kg) before conception, throughout pregnancy, and while weaning and compared to an unexposed group. Offspring from each group were followed to 3 weeks or 3 months of age, and their blood and liver samples were collected. Body weights and lipids were assessed at 3 weeks and 3 months while reproductive, gonadotropic, and thyroid hormones were assessed at 3 months. Prenatal AFB1 (high dose) exposure resulted in significant 16.3%, 31.6%, and 7.5% decreases in weight of the offspring at birth, 3 weeks, and 3 months, respectively. Both doses of exposure altered lipid and hormone profiles. Pyrosequencing was used to quantify percent DNA methylation at tumor suppressor gene Tp53 and growth-regulator H19 in DNA from liver and blood. Results were compared between the control and AFB1 exposure groups in 3-week liver samples and 3-week and 3-month blood samples. Relative to controls, Tp53 DNA methylation in both low- and high-dose exposed rats was significantly decreased in liver samples and increased in the blood (p < 0.05 in linear mixed models). H19 methylation was higher in the liver from low- and high-exposed rats and decreased in 3-month blood samples from the high exposure group (p < 0.05). Further research is warranted to determine whether such hormone, lipid, and epigenetic alterations from AFB1 exposure early in life play a role in the development of early-onset HCC.

The generation of reactive oxygen species (ROS) plays an essential role in the pathogenesis of several diseases. Its implication in inflammation has suggested a possible link between oxidative stress and activation/release of cytokines in precancerous states. Recent observational studies have suggested an association between inflammation and vitamin D deficiency; hence, suggesting that vitamin D could play a role in the pathogenesis of diseases. This study examined the antioxidant and anti-inflammatory potentials of vitamin D in diethylnitrosamine (DEN)-induced oxidative stress and inflammation in rats. Rats were divided into four experimental groups. While groups one and two were administered twice weekly with 30 mg/kg body weight DEN for six weeks, groups three and four were given normal saline. Groups one and three were fed with vitamin D deficient diet, while groups two and four were fed vitamin D diet during the experiment. After that, biomarkers of oxidative stress status were assayed spectrophotometrically. The concentration of inflammatory cytokines was determined using enzyme-linked immunosorbent assay (ELISA). DEN-induced vitamin D deficient diet group had increased antioxidant enzymes’ activities. Also, there were elevated concentrations of thiobarbituric acid reactive substances (TBARS) and inflammatory cytokines in the same group. Vitamin D diet, however, reduced oxidative stress effects through the reduction in the activities of TBARS and caused a significant ( p < 0.05 ) increase in nitric oxide concentration. Vitamin D diet significantly ( p < 0.05 ) reduced the level of interleukin 1β and TNF-α produced in the deficiency state. These findings show that vitamin D may play an essential role in the regulation of hepatic oxidative stress and inflammatory responses.