John I. Anetor

Cadmium level in pregnancy, influence on neonatal birth weight and possible amelioration by some essential trace elements.

Cadmium (Cd) is currently of great concern in rapidly industrializing countries-India, China. Their products consumed especially due to increase demand in many developing countries like Nigeria can result in adverse effects. Cd is a ubiquitous environmental pollutant and toxicant and humans are continually exposed to the toxic effects of Cd primarily through food as well as from environmental pollution through industrial activities. Maternal exposure to Cd has been associated with the delivery of low-birth weight babies and an increase incidence of spontaneous abortion. Cd a toxic metal can displace zinc (Zn) an essential element necessary for normal fetal development and growth. With this consideration, 160 subjects comprising of 125 pregnant and 35 non-pregnant subjects as controls were recruited for this study. The pregnant subjects were classified according to the three trimesters of pregnancy as followed; 35, 35, and 55 from the first to the third trimesters respectively. The third trimester subjects were followed-up until after delivery where neonatal parameters (birth weight, head circumference, and length) of babies were measured. 32 (58%) of the women delivered babies with normal birth weight, 19 women (35%) delivered babies with low-birth weight while four women (7%) delivered babies with high- birth weight. Subject who delivered low-birth weight babies had significantly higher Cd concentration and lower Zn concentration and body mass index when compared with those with normal weight babies. These results suggest that Cd indeed has some toxic effects on neonatal birth weight.

Depressed antioxidant status in pregnant women on iron supplements: pathologic and clinical correlates.

Iron (Fe) remains a commonly prescribed supplement in pregnancy. Its possible pathologic potential is either uncommonly considered or ignored. We determined the antioxidant status in pregnant women with and without Fe supplements. Fifty-eight apparently healthy pregnant women on Fe supplements were selected for the study from the antenatal clinic of the University College Hospital, Ibadan, Nigeria. Fifty-five aged matched pregnant women who were not on Fe from various parishes of the Christ Apostolic Church, Ibadan (non-drug using Christian sect) were randomly selected as controls. Both groups were classified according to the trimesters of pregnancy. The gestational age in both pregnant women on Fe supplements and non-supplement pregnant women was similar. Fruit and vegetables consumption was higher in the supplement than in the non-supplement group (57.2% vs. 37.3%). Anthropometric indices, weight, height, and BMI, were also similar. But while the weight of the Fe supplement group decreased by nearly 3% in the third trimester, it increased by over 10% (p < 0.00) in the non-supplement group in the same period. Serum Fe level was significantly higher in the supplement than the non-supplement group (p < 0.001). In contrast, the levels of the antioxidants, ascorbic acid, copper (Cu), zinc (Zn), and bilirubin were all significantly decreased (p < 0.05, p < 0.001, p < 0.05, and p < 0.05, respectively). Uric acid level though also lower in the supplement group did not reach statistical significance (p > 0.05), while vitamin E was similar in both groups. There was relative stability of all antioxidants except uric acid, which declined from the first to the last trimester in the non-supplement group. The significantly higher Fe level in the second trimester was sustained in the third trimester though to a lesser degree (p < 0.05) and associated with significant decreases in the following antioxidant levels in the supplement group, ascorbic acid, bilirubin, Cu, and Zn (p < 0.02, p < 0.02, p < 0.02, and p < 0.001, respectively). Uric acid and vitamin E though lower in the supplement group were not significantly different. Remarkably, percentage changes between the first and third trimesters revealed that serum Fe increased by over 116% in the Fe supplement group, while it only increased by over 50% in the non-supplement group. This was associated with 23.50% decrease in ascorbate level (p < 0.003) in the supplement group, while it decreased by only 3.70% in the non-supplement group (p > 0.05). Again vitamin E decreased by 17.22% in the supplement group, while it decreased by only 7.30% in the non-supplement group during the period. Uric acid and bilirubin levels decreased by similar proportions during the period, while Zn decreased by 18.55% in the supplement group and by 14.86% in the non-supplement group. In contrast Cu increased by 7.20% in the supplement group, while it increased by only 2.96 in the non-supplement group. Additionally, all the antioxidants in the supplement group except vitamin E, viz, ascorbic acid, bilirubin, Cu, uric acid, and Zn, were significantly inversely correlated with serum Fe level (r − 0.299, p < 0.05, r − 0.278, p < 0.05, r − 0.383, p < 0.05, and r − 0.0369, p < 0.05). These data imply markedly depressed antioxidant status in the Fe supplement pregnant group with attendant oxidative stress (most probably pro-oxidant Fe-induced). This is associated with molecular and cellular damage as well as a number of pathologic and clinical correlates that underlie the exacerbation of morbidity and mortality in maternal and child populations, particularly in the developing countries. This appears to call for serious caution and prior evaluation of antioxidant and Fe status and during the use of Fe supplements in pregnancy for monitoring and prognostic purposes and to avert or ameliorate oxidative stress-induced pathologies in maternal and fetal systems.

Decreased thiamine and magnesium levels in the potentiation of the neurotoxicity of lead in occupational lead exposure.

The relationship between blood lead (Pb) and serum levels of calcium and of neural nutrients such as thiamine and magnesium (Mg) has been determined in a Nigerian population that is occupationally exposed to Pb. Forty-seven male Pb workers were recruited as test subjects and 25 males unexposed to Pb served as controls. The test subjects were classified into three groups, based on severity of exposure to Pb. Blood lead (BPb) and the serum levels of Mg, thiamine, and calcium were determined in both test subjects and controls. The mean blood Pb level was not significantly higher in Pb workers. In contrast, Mg and thiamine levels were significantly decreased (p<0.05; p<0.01, respectively). However, the calcium level was not significantly lower in test subjects than in controls. Also, there was a significant negative correlation between serum thiamine and blood Pb levels (r=−0.50; p<0.01). Furthermore, there was a significant negative correlation between serum calcium and BPb levels (r=−0.41; p<0.01). This study has shown that relatively low BPb levels can enhance Pb absorption and also potentiate Pb neurotoxicity in the presence of decreased serum thiamine and Mg levels.

Increased plasma manganese, partially reduced ascorbate, 1 and absence of mitochondrial oxidative stress in type 2 diabetes mellitus: implications for the superoxide uncoupling protein 2 (UCP-2) pathway.

Oxidative stress is an important component of diabetes and its complications. Manganese (Mn), the key component of the Mitochondrial antioxidant (MnSOD), plays a key role in the superoxide uncoupling protein 2 (UCP-2) pathway in inhibiting of glucose-stimulated insulin secretion (GSIS). The interactions of Mn with ascorbate and other components of this pathway have not been defined in type-2 diabetes. Fifty established type 2 diabetics (30 males, 20 females) and 30 non-diabetics (controls; 18 males, 12 females) matched for age and sex were investigated. Dietary intake, particularly of micronutrients as assessed by 24-h dietary recall was similar between diabetics and controls. Weight and height of all subjects were determined and body mass index (BMI) computed after clinical assessment. Fasting plasma glucose, manganese, ascorbic acid, creatinine and K+ levels were determined; K+ was to assess the K+ channels, whereas creatinine was to assess probability of oxidative stress nephropathy. Body mass index was greater in DM than in controls (p < 0.001). Fasting plasma glucose and Mn levels (p < 0.00 and p < 0.01, respectively) were higher in diabetes than in the controls. Manganese level was greater than twice the levels in controls. Ascorbic acid was not significantly different (p > 0.05), but was 50% lower than the level in non-diabetics. Potassium like Mn and glucose was significantly higher in diabetes mellitus (DM) than in controls (p < 0.001). Creatinine was not significantly different between diabetics and controls (p > 0.05). Correlations among all parameters were not significantly different. These findings suggest absence of significant oxidative stress in the mitochondria, probably excluding a role for UCP-2-superoxide pathway in the inhibition of glucose-stimulated insulin secretion (GSIS), calling for caution in the precocious conclusion that interruption of UCP-2 activity may provide a viable strategy to improve β-cell dysfunction in type 2 diabetes mellitus.

Altered Copper Level and Renal Dysfunction in Nigerian Women Using Skin-Whitening Agents

The purpose of the study was to determine the concentration of trace elements in serum samples of women who are chronic users of skin-whitening agents as well as the hepatic and renal effects of these agents on these women. The study was conducted among 23 skin-whitening users while 25 women served as the controls. The serum concentrations of Zn, Mn, and Mg were not significantly changed in these women compared with controls (p > 0.05), but Cu was significantly increased in skin-whitening agent users compared with controls (p < 0.05). Serum urea and creatinine were significantly increased compared with the controls (p < 0.05). Moreover, ALT, AST, albumin, total protein, and bilirubin were not significantly changed (p > 0.05). The significant increase in the levels of renal indices shows that these agents might be nephrotoxic after prolonged usage while increase in copper level with accompanying renal dysfunction may be an indication that copper mediates in oxidative-induced renal dysfunction. However, further study is needed to identify the cause and source of high serum copper as many of the herbal extracts may be rich sources of copper. Moreover, a large population study may be necessary to examine the exact correlation between copper and renal indices.

Sex Hormones, Oestrogen Receptor, Progesterone Receptor and Human Epithelial Receptor 2 Expressions in Pre and Postmenopausal Sub-Saharan African Women with Breast Cancer

Aim: This study was carried out to determine the serum levels of sex hormones and gonadotropins as well as the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epithelial receptor 2 (HER 2) in pre and postmenopausal women with breast cancer. Study Design: Case-control study. Place and Duration of Study: Surgical Oncology Clinic, University College Hospital, Ibadan, Nigeria between April 2011 and July 2014. Methodology: 169 non-pregnant women aged 48.3±1.3 years were recruited for this study. They comprised of 85 histologically confirmed breast cancer pre-therapy (cases) matched with 84 Original Research Article Ajayi et al.; JCTI, 3(4): 1-11, 2016; Article no.JCTI.25259 2 apparently healthy women without breast cancer (controls) according to age and menstrual phase. Both cases and controls were subdivided into pre and postmenopausal groups (54 premenopausal cases; 31 postmenopausal cases; 53 premenopausal controls; 31 postmenopausal controls respectively). Anthropometry and reproductive history were obtained by standard methods. Blood (10ml) was obtained from participants and centrifuged to obtain serum. Oestradiol, progesterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined using enzyme immunoassay (EIA). Expression of ER, PR and HER 2 were determined by immunohistochemistry. Data analysed by Chi-square, Student’s t-test and multiple regression were considered statistically significant at p<0.05. Results: All premenopausal cases (100%) had ER and PR receptor negative expressions out of which 46(88.5%) had HER 2 receptor negative expression. Oestradiol and progesterone were significantly higher in postmenopausal cases compared with controls (p<0.05) while FSH and LH were significantly higher in premenopausal cases than controls (p<0.05). Conclusion: The pathophysiology of breast cancer may be based on menstrual phase. Elevated gonadotropins and sex hormones may be important in premenopausal and postmenopausal women with breast cancer. Triple negative breast cancer observed in 88.5% of premenopausal women with breast cancer is critical in the management of the disease especially in younger women.

Cadmium Level, Glycemic Control, and Indices of Renal Function in Treated Type II Diabetics: Implications for Polluted Environments.

Cadmium (Cd) has recently emerged as a major concern not only in environmental toxicology but also in metabolic diseases such as diabetes mellitus and its complications. Conflicting data aside, these studies have not been examined in a clinical population undergoing management as well as possible modulation by the prominent metabolic antagonist of Cd such as zinc (Zn). This study examined the relationship between cadmium levels, glycemic control, and renal pathology in established type II diabetic patients with focus on populations exposed to modern environmental health hazards (MEHHs). Sixty-five participants, consisting of 45 type-2 diabetics and 20 non-diabetics were enrolled for the study, mean age 61.51 ± 5.27 years. Glycated hemoglobin (HbA1c) was used to classify them into three sub-groups: (A) good glycemic control (44.4%), (B) fair glycemic control (24.4%), and (C) poor glycemic control (31.1%). Plasma levels of glucose, Cd, Zn, HbA1c, creatinine, urinary creatinine, microalbuminuria, and estimated glomerular filtration rate (eGFR) were determined in all participants using standard methods. Fasting plasma glucose was higher in diabetics than in non-diabetics (p = 0.000) as well as Zn level, though not significantly. Interestingly, Cd level, Cd/Zn ratio, and urinary creatinine were significantly lower in diabetics than in non-diabetics. The group with poor glycemic control (C) had significantly higher Cd level compared to the one with good glycemic control (group A). The renal function revealed that microalbuminuria and urinary albumin/creatinine ratio (UACR) was significantly higher in diabetics than in non-diabetics, while eGFR was found to be similar in both diabetics and non-diabetics. UACR inversely correlated with Cd level, while plasma creatinine level positively correlated with Cd but not significantly. Correlation between Cd and HbA1c revealed non-significant inverse correlation (r = −0.007; p > 0.05), while Zn showed a significant inverse correlation with Cd (r = −0.317; p < 0.014). The lower Cd level in diabetics compared to non-diabetics probably reflects the modulating effect of Zn in treated diabetics given nutritional education in addition to their regular regime, including good sources of Zn. The renal insufficiency with increasing Cd level may suggest that the progression of renal impairment may not be responsive to the putative modulating effect of Zn.

Ascorbic Acid Supplementation and Spermatogenesis in Nigerian Men

Background: The role of ascorbic acid as an antioxidant nutrient in the maturation of sperm cells has received considerable attention. A previous study from our laboratory showed reduced seminal and plasma ascorbic acid in subfertile patients. Method: Fifteen subfertile male patients mean age 36.4±0.9 years with sperm counts of 31.4±7, 08 x10 6 /cm 3 were given 200mg/day dose of ascorbic acid as supplement for four weeks and ten highly fertile male mean age 35.6±1.7 years with sperm count of 50.9±10.3 x10 6 /cm 3 volunteers were selected as controls. The biochemical parameters and anthropometric measurements were determined using standard methods. Result: Significant decreases were obtained in baseline sperm cell count (p<0.01), percentage (%) motility and %vitality (p<0.01), and the % of morphologically normal sperm cells (p<0.01) in the subfertile compared with the controls. The baseline plasma and seminal ascorbic acid concentrations were significantly reduced (p<0.001). The post-supplementation sperm cell count (p<0.001), % motility and %vitality (p<0.01) were significantly increased compared with the baseline values. Conclusion: The enhanced reversal of poor semen quality and semen ascorbic acid status with dietary supplementation of vitamin C in subfertile is a pointer to its positive role in the maintenance of sperm cell integrity. Further work is therefore required to elucidate our findings. Keyword: Ascorbic acid, high density lipoprotein, cholesterol, semen, infertility subfertile.

Pituitary, Gonadal, Thyroid Hormones and Endocrine Disruptors in Pre and Postmenopausal Nigerian Women with ER-, PR- and HER-2-Positive and Negative Breast Cancers

Breast cancer is broadly sub-divided into hormone responsive and non-hormone responsive subtypes. Estradiol has been associated with hormone responsive breast cancers. There is, however, a paucity of information on the role of sex hormones, gonadotropins, and thyroid hormone in non-hormone responsive breast cancer. This study aimed to determine differences in the serum levels of sex hormones, gonadotropins, thyroid hormones, and endocrine disruptors (lead, cadmium, and arsenic) in Nigerian women with hormone responsive and non-hormone responsive breast cancers. Seventy-nine non-pregnant women aged 28–80 years with histologically confirmed breast cancer were recruited, pre-therapy, into this cross-sectional study. They comprised 52 premenopausal women and 27 postmenopausal women recruited from the Surgical Oncology Clinic of the Department of Surgery, University College Hospital, Ibadan. Comparison of biochemical parameters were based on the positivity (+) and negativity (−) of estrogen receptor (ER), progesterone receptor (PR) and human epithelial receptor-2 (HER-2). Estradiol, progesterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were determined using enzyme immunoassay (EIA). Serum lead, cadmium and arsenic were determined using atomic absorption spectrophotometry (AAS). Expression of ER, PR and HER2 were determined using immunohistochemistry. Data was analyzed using Mann-Whitney U-test and multiple regression, with p < 0.05 considered as being statistically significant. Estradiol and progesterone were significantly higher in breast cancer participants with ER− and PR− compared with those with ER+ and PR+ breast cancer (p < 0.05). Follicle stimulating hormone and LH levels were significantly higher in participants with ER+ and PR+ breast cancer compared with participants with ER− and PR− breast cancer (p < 0.05). Arsenic was inversely related with TSH in premenopausal participants with ER− and PR− (β = −0.305; β = −0.304, respectively). Sex hormones and gonadotropins appear to be involved in the pathogenesis of triple negative and luminal breast cancer, respectively.

Chemical Carcinogenesis: Risk Factors, Early Detection and Biomedical Engineering

Cancer is now recognized in both humans and in other multicellular animals as arising from a number of different causes, including specialized viruses, radiation, chemicals, certain highly irritative parasites (inflammation) and a number of other factors, such as specific genetic defects present in individual humans and possibly in every member of a colony of specially bred animal models. Cancer from non genetic causes largely from environmental factors, of which chemicals have a disproportionate share, is believed to contribute nearly 70% of all cancer cases. Chemical carcinogenesis originally derives from experimental induction of malignant skin tumor in mice with chemicals. Early studies indicated some agents such as polycyclic aromatic hydrocarbons (PAH) could cause cancer of the skin if they were painted on to mice in high doses. These early studies also showed that the induction of cancer was dose dependent; in low dosage they would not cause cancer but would render the skin susceptible to developing cancer on exposure to another agent, which, on its own would not induce cancer. Thus at the dawn of the 20th century, it was recognized that chemicals cause cancer; though individual cancer causing molecules had not yet been identified, nor their cellular targets clearly known. It was however clearly understood that carcinogenesis, at the cellular level, was predominantly an irreversible process. Knowledge of the mechanisms by which chemicals cause cancer and the molecular changes that characterize tumor progression was lacking. The origin of the understanding that cancer had a cause was first pointed out by the Italian investigator, Ramazini in 1700. Seven and a half decades later, the British Surgeon, Percival Pott made the connection between exposure to soot, rich in hydrocarbons and scrotal cancer (Pott, 1775). It is now known that at the most fundamental level, cancer is caused by abnormal gene expression. This abnormal gene expression occurs through a number of mechanisms, including direct damage to the DNA, and inappropriate transcription and translation of cellular genes. The contribution of chemicals to the carcinogenic process is well known to have increased given the parallel between industrialization with associated increased chemical production and utilization and the prevalence of cancer.