Accumulation trends and patterns of some heavy metals in liver of Wistar rats following exposure to contaminated water

Heavy metals are known to cause damage through indirect oxidative effects. A comparative study on the bioavailability and liver accumulation of lead (Pb), cadmium (Cd), and mercury (Hg) in rats following continuous exposures to Hg (10 ppm), Cd (200 ppm) and Pb (100 ppm) in drinking water was carried out for six weeks. The accumulations in the liver were determined using AAS. Analysis gave evidence that the rate of change was not the same for all three metals for all three periods of time; there was statistically (p<0.05) significant interaction between the types of metal and time in their relationship to levels accumulation of the metals. While Hg and Pb showed peak accumulation at the second week of exposure, there was decrease in accumulation by the fourth and sixth week. Cd on the other hand showed a continuous increase in accumulation over the six weeks of study. Results indicate that the heavy metal concentration in the liver is under some physiological control, which may involve the chemistry of these metals resulting in different uptake, accumulation and elimination rates from the liver.Keywords: cadmium, lead, mercury, liver, accumulation patter

Effect of Vitamin C Supplementation on platelet aggregation and serum electrolytes levels in streptozotocin-induced diabetes mellitus in rats

Diabetes mellitus (DM) is a disease condition characterised by hyperglycemia; free radical and abnormal haematological indices. Vitamin C can reduce free radical generation and ameliorate adverse conditions of diabetes mellitus. The aim of the present study is to investigate the effect of vitamin C on platelet aggregation and electrolyte levels in Type 1 DM. Male Wistar rats were divided into four groups namely control, DM, DM +Vitamin C and Vitamin C groups. Rats were made diabetic with a single dose of streptozotocin (65 mg/kg) intraperitoneally. Vitamin C was administered orally to diabetic and normal rats at 200 mg/kg body weight for 28 days. Blood samples were analyzed for hematological parameters, platelet aggregation, and serum electrolyte levels. Blood glucose in DM+ Vitamin C group (9.9 ± 1.8 mmol/L) was significantly reduced (p<0.01) compared to DM group (32.2 ± 2.1 mmol/L) and significantly higher (p<0.05) than control (4.4 ± 0.8 mmol/L). Haemoglobin (Hb) concentration in DM group (12 ± 0.1 g/dL) was significantly reduced (p<0.01) when compared with control groups (14 ± 0.24 g/dL) and significantly increased (p<0.05) in the DM+vitamin C group (13.5 ± 0.5 g/dL) compared with the diabetic group. The mean corpuscular volume values in DM (68.66 ± 0.5 fL) and DM+vitamin C groups (68.11 ± 0.4 fL) were significantly higher (p<0.01) than the control (59.49 ± 0.5fL). Platelet count in DM group (523 ± 8.5 x109/L) was significantly raised (p<0.01) when compared to control (356 ± 6.2 x109/L) and significantly reduced (p<0.01) in DM+ vitamin C-treated group (385 ± 7.8 x109/L) compared with DM group. Platelet aggregation and serum sodium/potassium ratios was significantly reduced (p<0.01) in DM+vitamin C compared with DM group. These results suggest that oral vitamin C administration increases haemoglobin, reduced plasma glucose level, platelet count, serum sodium/potassium ion ratio and inhibits platelet aggregation in streptozotocin-induced DM in rats.Keywords: Diabetes mellitus, electrolytes, Haematological parameters, Platelet aggregation, Red cell indices, Vitamin

Phytowaste as nutraceuticals in boosting public health

AbstractThe utilization of bioactive constituent of peels and seeds provide an effective, environment friendly and inexpensive therapy for different forms of human disease, and the production, improvement and documentation of novel nutraceuticals. This review systematically presents findings and further understanding of the reported benefits and therapeutic applications of peel and seed extracts on innovative cell culture and animal studies, as well as phased clinical human trial research. The extracts of seed and peels were reported to possess high quantities of bioactive substances with antioxidative, antidiabetic, hepatorenal protective, antithyroidal, anti-inflammatory, antibacterial, cardiovascular protective, neuro-protective effects, anticancer and wound healing activities. Therapeutic activities of the bioactive substances of peel and seed extracts include elevation of Superoxide dismutase (SOD), GSH-Px, t-GPx, Catalase and GST activities, with the suppression of MDA levels, hydroperoxide generation and lipid peroxidized products, the extracts also regulate inflammatory mediators and cytokines as they are reported to suppress the secretion of inflammatory cytokines, which include; IL-1β, PGE2, TGF-β and TNF-α and induces apoptosis and cell differentiation. This review revealed the therapeutic importance and best utilization of peels and seed extracts of fruits and vegetables

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

8-Oxo-9-Dihydromakomakine Isolated from <i>Aristotelia chilensis</i> Induces Vasodilation in Rat Aorta: Role of the Extracellular Calcium Influx

8-Oxo-9-dihydromakomakine is a tetracyclic indole alkaloid extracted from leaves of the Chilean tree Aristotelia chilensis. The present study investigated the effects of this alkaloid on vascular response in tissues isolated from aortic segments obtained from normotensive rats. Our results showed that 8-oxo-9-dihydromakomakine induced a dose-dependent relaxation of aortic rings pre-contracted with phenylephrine (PE; 10&#8722;6 M). The vasorelaxation induced by 8-oxo-9-dihydromakomakine in rat aortic rings is independent of endothelium. The pre-incubation of aortic rings with 8-oxo-9-dehydromakomakine (10&#8722;4 M) significantly reduced the contractile response to KCl (p &lt; 0.001) more than PE (p &lt; 0.05). The highest dose of 8-oxo-9-dehydromakomakine (10&#8722;4 M) drastically reduced the contraction to KCl (6&#183;10&#8722;2 M), but after that, PE (10&#8722;6 M) caused contraction (p &lt; 0.05) in the same aortic rings. The addition of 8-oxo-9-dihydromakomakine (10&#8722;5 M) decreased the contractile response to tetraethylammonium (a voltage-dependent potassium channels blocker; TEA; 5 &#215; 10&#8722;3 M; p &lt; 0.01) and BaCl2 (a non-selective inward rectifier potassium channel blocker; 5 &#215; 10&#8722;3 M; p &lt; 0.001) in rat aorta. 8-oxo-9-dihydromakomakine (10&#8722;5 M) decreased the contractile response to PE in rat aorta in the presence or absence of ouabain (an inhibitor of Na,K-ATPase; 10&#8722;3 M; p &lt; 0.05). These results could indicate that 8-oxo-9-dihydromakomakine partially reduces plasma membrane depolarization-induced contraction. In aortic rings depolarized by PE, 8-oxo-9-dihydromakomakine inhibited the contraction induced by the influx of extracellular Ca2+ in a Ca2+ free solution (p &lt; 0.01). 8-oxo-9-dihydromakomakine reduced the contractile response to agonists of voltage-dependent calcium channels type L (Bay K6844; 10&#8722;8 M; p &lt; 0.01), likely decreasing the influx of extracellular Ca2+ through the voltage-dependent calcium channels. This study provides the first qualitative analysis indicating that traditional folk medicine Aristotelia chilensis may be protective in the treatment of cardiovascular pathologies

Novel Oxime Synthesized from a Natural Product of <i>Senecio nutans</i> SCh. Bip. (Asteraceae) Enhances Vascular Relaxation in Rats by an Endothelium-Independent Mechanism

Senecio nutans Sch. Bip. and its constituents are reported to have antihypertensive effects. We isolated metabolite–1, a natural compound from S. nutans (4-hydroxy-3-(isopenten-2-yl)-acetophenone), and synthesized novel oxime – 1 (4-hydroxy-3-(isopenten-2-yl)-acetophenoxime) to evaluate their effect on vascular reactivity. Compounds were purified (metabolite–1) or synthetized (oxime–1) and characterized using IR and NMR spectroscopy and Heteronuclear Multiple Quantum Coherence (HMQC). Using pharmacological agents such as phenylephrine (PE) and KCl (enhancing contraction), acetylcholine (ACh), L-NAME (nitric oxide (NO) and endothelial function), Bay K8644-induced CaV1.2 channel (calcium channel modulator), and isolated aortic rings in an organ bath setup, the possible mechanisms of vascular action were determined. Pre-incubation of aortic rings with 10−5 M oxime–1 significantly (p 50 to KCl significantly (p p −7 to 10−5 M) by a mechanism that decreases Cav1.2-mediated Ca2+ influx from the extracellular space and reduces Ca2+ release from intracellular stores. At a submaximal concentration (10−5 M), oxime–1 caused a significant relaxation in rat aorta even without vascular endothelium or after pre-incubate the tissue with L-NAME. Oxime–1 decreases the contractile response to PE by blunting the release of Ca2+ from intracellular stores and blocking of Ca2+ influx by channels. Metabolite–1 reduces the contractile response to KCl, apparently by reducing the plasma membrane depolarization and Ca2+ influx from the extracellular space. These acetophenone derivates from S. nutans (metabolite–1 and oxime–1) cause vasorelaxation through pathways involving an increase of the endothelial NO generation or a higher bioavailability, further highlighting that structural modification of naturally occurring metabolites can enhance their intended pharmacological functions

Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta

Alkaloids derived from plants have shown great medicinal benefits, and are often reported for their use in cardiovascular disease management. Aristotelia chilensis (Molina) Stuntz (Maqui) has shown important medicinal properties in traditional useage. In this study, we evaluated the effect of the indole-alkaloid aristoteline (ARI), isolated from leaves of Maqui, on vascular reactivity of isolated aortic rings from normotensive rats. ARI induced relaxation (100%) in a concentration-dependent manner in intact or denuded-endothelium aortic rings pre-contracted with phenylephrine (PE; 1 &mu;M). However, a specific soluble guanylyl cyclase inhibitor (ODQ; 1 &mu;M) significantly reduced the relaxation to ARI in aortic rings pre-contracted with PE. In the presence of ARI, the contraction induced by KCl or PE was significantly (p &lt; 0.05) decreased. Interestingly, the potassium channel blockade with 10 &mu;M BaCl2 (Kir), 10 &mu;M glibenclamide (KATP), 1 mM tetraethylammonium (TEA; KCa1.1), or 1 mM 4-aminopyridine (4-AP; Kv) significantly (p &lt; 0.05) reduced the ARI-induced relaxation. ARI significantly (p &lt; 0.05) reduced the contractile response to agonist of CaV1.2 channels (Bay K8644; 10 nM), likely reducing the influx of extracellular calcium through plasma membrane. The mechanisms associated with this process suggest an activation of the potassium channels, a calcium-induced antagonism and endothelium independent vasodilation that possibly involves the nitric oxide-independent soluble guanylate cyclase pathway

Comparative Effect of Type 1 and Type 2 Diabetes Mellitus on Vascular Responses of Rat Thoracic Aorta to Potassium Ion Channel Openers

Background: Diabetes mellitus is associated with many cardiovascular dysfunction and impairment of potassium channel function. Aim: We compared the vascular reactivity in aorta from streptozotocin-induced and Goto-Kakizaki (GK) diabetic rats to potassium channel openers. Methodology: Diabetes mellitus (DM) was induced in Sprague Dawley rats by intraperitoneal injection of streptozotocin (STZ) at 65 mg/kg body weight. After four weeks of DM, vascular reactivity of the aortic rings from STZ-induced Sprague Dawley and age-matched GK and control rats to phenylephrine, acetylcholine, levcromakalim and naringenin was studied using standard organ bath procedure. Results: The phenylephrine-induced contraction was significantly (P<0.05) increased in STZ-diabetic aortic rings [2.03 ±0.07 g] when compared with GK rats [1.47±0.14 g] and STZ-control [1.42±0.21 g]. Maximal relaxation and potency to acetylcholine, levcromakalim and (+/-)-naringenin were significantly (P<0.05) decreased in STZdiabetic aorta when compared with GK-diabetic and control groups. Conclusion: The phenylephrine-induced contraction, endothelium-dependent relaxation, KATP - and (+/-)-naringenin-induced vasorelaxation are not altered in the early stages of Type 2 diabetes whereas there is exaggerated contractile response and a relaxant dysfunction involving the endothelium, KATP in Type 1 diabetes mellitus