Polychlorinated Biphenyls-Induced Oxidative Stress on Rat Hippocampus: A Neuroprotective Role of Quercetin

Present study is aimed to evaluate the ameliorative role of quercetin on PCBs-induced oxidative stress in hippocampus of Wistar rats. Group I rats received vehicle (corn oil) intraperitoneally (i.p); Group II received quercetin 50 mg/kg bwt/day (gavage); Group III received PCB 2 mg/kg bwt/day (i.p); Group IV received PCB (i.p) and simultaneously quercetin through gavage. After 30 days, rats were euthanized and hippocampus was dissected from each rat brain. Oxidative stress was assessed by determining the levels of H2O2, LPO, Pcc, and alteration in the functional markers such as CK, AchE, and ATPases activities in the hippocampus of control and experimental animals. A significant increase in the levels of stress markers and decrease in level of functional markers were observed in PCBs-treated rats. Moreover DNA fragmentation and histological studies were ascertained to confirm PCBs toxicity. In conclusion, quercetin shows a protective role against PCBs-induced oxidative damage in rat hippocampus

HYPOMAGNESAEMIA AND HYPOCALCAEMIA THE MAJOR MISSED OUT CLINICAL CONDITION IN THE MANAGEMENT OF DIABETES

Magnesium (Mg) and Calcium (Ca) is one of the essential factors for the insulin to get released from the pancreatic cell. To evaluate the relation of hypomagnesemia and hypocalcaemia in the glycaemic control and to analyse the importance of both Mg and Ca in the insulin secretion mechanism. The study was conducted in the laboratory department, Billroth hospitals. A total of 239 individuals were selected for this study, HbA1c level, serum magnesium and calcium were assessed for all the individuals and in addition to this serum electrolytes were also checked. Out of 239 individuals, 79 were found out as uncontrolled diabetic by calculating HbA1c as a gold standard, males are higher in ratio compared to female. By studying serum magnesium and calcium level, hypocalcaemia is present in more individuals and females (31%) are much prone to both than males (20%). The different correlation was also analysed for hypomagnesemia and hypocalcaemia. The electrolytes like sodium (Na) and potassium (K) was analysed, females are highly affected by electrolyte imbalance but in hypomagnesemia diabetic individuals the males are high in electrolyte imbalance. Since Mg and Ca plays a vital role in insulin synthesis, secretion, repair, and the alteration, along with the hypoglycaemic agents the supplementation of magnesium or calcium could be suggested via, dietary or drug supplements. In addition to this, regular monitoring of electrolytes is essential to maintain fluid balance

HYPOMAGNESAEMIA AND HYPOCALCAEMIA THE MAJOR MISSED OUT CLINICAL CONDITION IN THE MANAGEMENT OF DIABETES

Magnesium (Mg) and Calcium (Ca) is one of the essential factors for the insulin to get released from the pancreatic cell. To evaluate the relation of hypomagnesemia and hypocalcaemia in the glycaemic control and to analyse the importance of both Mg and Ca in the insulin secretion mechanism. The study was conducted in the laboratory department, Billroth hospitals. A total of 239 individuals were selected for this study, HbA1c level, serum magnesium and calcium were assessed for all the individuals and in addition to this serum electrolytes were also checked. Out of 239 individuals, 79 were found out as uncontrolled diabetic by calculating HbA1c as a gold standard, males are higher in ratio compared to female. By studying serum magnesium and calcium level, hypocalcaemia is present in more individuals and females (31%) are much prone to both than males (20%). The different correlation was also analysed for hypomagnesemia and hypocalcaemia. The electrolytes like sodium (Na) and potassium (K) was analysed, females are highly affected by electrolyte imbalance but in hypomagnesemia diabetic individuals the males are high in electrolyte imbalance. Since Mg and Ca plays a vital role in insulin synthesis, secretion, repair, and the alteration, along with the hypoglycaemic agents the supplementation of magnesium or calcium could be suggested via, dietary or drug supplements. In addition to this, regular monitoring of electrolytes is essential to maintain fluid balance

ROLE OF INTERPRETATIVE REMARKS IN CLINICAL BIOCHEMISTRY-A PERSPECTIVE OF MEDICAL BIOCHEMIST

It is a professional requirement for clinical biochemists to provide Interpretative Remarks (IR). Few clinical labs give any comments at all, and the majority of laboratories just employ pre-written remarks on the report. In addition to physicians, other medical professionals, and occasionally even patients themselves, seek laboratory experts for guidance on data interpretation. The quality of interpretative remarks is impacted by the unavailability of the patient's medical record, restricted communication with the doctors, and a lack of professional experience. The purpose of this paper is to highlight how crucial it is to provide interpretive commentary in the context of responsibility for medical biochemists. In a similar vein, this paper offers guidance to those who offer interpretations

Impact of quercetin on tight junctional proteins and BDNF signaling molecules in hippocampus of PCBs-exposed rats

Abstract Polychlorinated biphenyls (PCBs) consist of a range of toxic substances which are directly proportional to carcinogenesis and tumor-promoting factors as well as having neurotoxic properties. Reactive oxygen species, which are produced from PCBs, alter blood–brain barrier (BBB) integrity, which is paralleled by cytoskeletal rearrangements and redistribution and disappearance of tight junction proteins (TJPs) like claudin-5 and occludin. Brain-derived neurotrophic factor (BDNF), plays an important role in the maintenance, survival of neurons and synaptic plasticity. It is predominant in the hippocampal areas vital to learning, memory and higher thinking. Quercetin, a flavonoid, had drawn attention to its neurodefensive property. The study is to assess the role of quercetin on serum PCB, estradiol and testosterone levels and mRNA expressions of estrogen receptor α and β, TJPs and BDNF signaling molecules on the hippocampus of PCBs-exposed rats. Rats were divided into 4 groups of 6 each. Group I rats were intraperitoneally (i.p.) administered corn oil (vehicle). Group II received quercetin 50 mg/kg/bwt (gavage). Group III received PCBs (Aroclor 1254) at 2 mg/kg bwt (i.p). Group IV received quercetin 50 mg/kg bwt (gavage) simultaneously with PCBs 2 mg/kg bwt (i.p.). The treatment was given daily for 30 days. The rats were euthanized 24 h after the experimental period. Blood was collected for quantification of serum PCBs estradiol and testosterone. The hippocampus was dissected and processed for PCR and Western blot; serum PCB was observed in PCB treated animals, simultaneously quercetin treated animals showed PCB metabolites. Serum testosterone and estradiol were decreased after PCB exposure. Quercetin supplementation brought back normal levels. mRNA expressions of estrogen α and β were decreased in the hippocampus of PCB treated rats. TJPS and BDNF signalling molecules were decreased in hippocampus of PCB treated rats. Quercetin supplementation retrieved all the parameters. Quercetin alone treated animals showed no alteration. Thus in PCB caused neurotoxicity, quercetin protects and prevents neuronal damage in the hippocampus.</jats:p

Abstract 1310: SLC5A8 functions as a tumor suppressor through redistribution and depletion of survivin

Abstract SLC5A8 is a Na+-coupled transporter for lactate, pyruvate, and nicotinate. Its expression is silenced in a wide variety of cancers including breast, colon, brain, thyroid, prostate, and pancreas, by methylation of CpG islands of its promoter. Increasing SLC5A8 expression through inhibition of DNA methylation in cancer cells leads to apoptosis. The silencing of SLC5A8 is essential for tumor cell survival because of the ability of this transporter to increase cellular levels of pyruvate by actively transporting circulating pyruvate into cells. Pyruvate is considered as an efficient fuel source for tumor cells, but our studies have shown that this metabolite is actually a tumor suppressor through its ability to inhibit HDAC1 and HDAC3. Our recent studies have shown that HDAC inhibition alone is not responsible for the tumor suppressive function of SLC5A8. Survivin, an anti-apoptotic protein and also a chromosomal passenger complex protein, is sequestered to the plasma membrane by SLC5A8 through protein-protein interaction and is also downregulated by transcriptional inhibition. This phenomenon is seen in two different human breast cancer cell lines, MCF7 and MB231. These cell lines do not express SLC5A8, and survivin is localized predominantly in the nucleus in these cells. However, upon lentiviral-mediated expression of SLC5A8 in these cells, survivin gets depleted in the nucleus but gets concentrated in the plasma membrane, colocalizing with the transporter. In the absence of SLC5A8, survivin localizes at the centromere during metaphase, and is essential for recruitment of the other component of the chromosomal passenger complex, Aurora B, to the centromere. But SLC5A8-induced translocation of survivin out of the nucleus disrupts the chromosomal passenger complex and consequently interferes with cell division. Additionally, apoptosis is induced in these cells upon forced expression of the transporter. Redistribution of survivin from the nucleus to the plasma membrane is not the only change observed in breast cancer cells upon SLC5A8 expression. The total cellular pool of survivin is also decreased, resulting from decreased transcription of the survivin gene. This process is associated with decreased phosphorylation of STAT3. The redistribution and depletion of survivin in these breast cancer cells upon SLC5A8 expression increases their sensitivity to chemotherapeutic agents. All these effects are independent of HDAC inhibition because these effects are seen in the absence of pyruvate in the culture medium. The growth of MB231 cells in mouse xenografts is drastically reduced when SLC5A8 is expressed. We conclude that SLC5A8 functions as a tumor suppressor by two different mechanisms, one involving HDAC inhibition in the presence of pyruvate and the other involving survivin redistribution and depletion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1310. doi:1538-7445.AM2012-1310</jats:p