Open Access Minireview Article

Mini-Review: The Influence of Respiratory and pH Imbalance in Cancer Development

Gabi Drochioiu

International Journal of Biochemistry Research & Review, Page 386-409
DOI: 10.9734/IJBCRR/2014/8617

Aims: In this review, we bring further evidence in support of the hypothesis on the so-called respiratory and pH imbalance (RpHI) as a cause of long standing hypoxia within the whole organism, characteristic to the preneoplastic stage.

Background:  Carcinogenesis is a process by which normal cells are transformed into cancer cells. Cancer is a multifactorial disease with contributions from environmental, genetic and lifestyle factors. Cancer prevention is a global priority, yet the proximate causes of most cancers are still little understood. However, under hypoxic conditions, the overbusy cells, getting less oxygen than needed, turn into anaerobic adenosine triphosphate (ATP) production, excessive multiplication and finally, tumor development. Since hypoxia depends on the intensity and duration of action of the stress agent, human and animal organisms may compensate hypoxia only if the causal agent stops acting continuously. Cancer prevention might be associated with an increase in oxygen delivery to overstressed cells, carbon dioxide removing, as well as pH and glucose concentration balancing. The role of RpHI in chemical carcinogenesis and cancer incidence is also discussed.

Conclusion: Evidence from the literature data is brought to show that cancers develop at the physiological level, while the molecular changes in cancer cells are the consequence and not the main cause of malign processes. A link between the Warburg effect and the Macovschi’s biostructural theory was suggested.

Open Access Original Research Article

Effect of Plant Spices (Thymus vulgaris, Murraya koenigii, Ocimum gratissimum, Piper guineense) on Hemoglobin Glycation, Selected Enzymes and Red Blood Cell Indices in Alloxan-induced Diabetic Rats

Emmanuel Iroha Akubugwo, Solomon Nwanze Ekoh, Victor Chibueze Ude, Jude Maduabuchi Kamah

International Journal of Biochemistry Research & Review, Page 358-366
DOI: 10.9734/IJBCRR/2014/7202

Aim: The aim of this study was to determine the effect of plant spices (Thymus vulgaris, Murraya koenigii, Ocimum gratissimum and Piper guineense) on hemoglobin glycation (HbA1c), lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G6PD) and red blood cell (RBC) indices in alloxan- induced diabetic rats.

Study Design: The animals were grouped into six of 5 rats each. Groups II, III, IV, V and VI were induced diabetes by intraperitoneal injection of alloxan monohydrate with a dose of 170mg/kg body weight. Group I was the control, group II diabetic control and group III to VI were the experimental group. Crude aqueous extracts (500mg/kg body weight) of the spices were orally administered to the rats.

Methodology: Blood samples were collected by cardiac puncture after fasting overnight and standard methods were used for the extraction of spices and, determination of biochemical and hematological parameters.

Place and Duration of Study: The study was carried out at Enugu State University Teaching Hospital from September 2012 to January 2013.

Result: The result showed that glycated hemoglobin, fasting blood sugar and lactate dehydrogenase decreased significantly (P<0.05) while, glucose-6-phosphate dehydrogenase increased significantly (P<0.05) compared to diabetic control group but, no significant difference (P<0.05) was observed compared to normal control group. There were no significant differences (P<0.05) in red blood cell indices compared to diabetic control and normal control.

Conclusion: This study suggested that the spices extracts can be used to control diabetes and prevent its complications on antioxidant enzymes.

Open Access Original Research Article

Role of the Trp-disulfide Triads in the UV Light Induced Degradation of a Monoclonal Antibody scFv

Eszter Illyés, Stephanie Staelens, Vanhooren ., Hans Deckmyn, Ignace Hanssens, Zsuzsa Majer

International Journal of Biochemistry Research & Review, Page 367-385
DOI: 10.9734/IJBCRR/2014/8453

Aims: Proteins are targets for photodegradation due to absorption of incident light by endogenous chromophores, e.g aromatic side chains. In this work we study the role of Trp-disulfide triads in the light induced loss of immunoglobulin activity.

Study Design: We investigated a single chain variable fragment (scFv) of the Trp-disulfide triad containing monoclonal antibody 82D6A3. The scFv binds to von Willebrand factor (VWF) and upon illumination with near UV-B-light the scFv partially loses its binding capacity to VWF. In order to relate this observed degeneration to the specific Trp-disulfide triads, we mutated W35(VL) and  W36(VH) which are in direct contact with the disulfide bridge of the VL and VH domain respectively, to Phe and compared the effects upon illumination of these mutants and the wild type scFv.

Methodology: We constructed and expressed three mutants, then tested the binding affinity of wild type and mutants to VWF. To study whether illumination caused protein fragmentation (rapture of disulfide bridge, structural changes, number of evolved thiols) we performed fluorescence spectroscopy, western blot and SDS-PAGE.

Results: Upon illumination with near UV-B-light the scFv partially lost its capacity to bind to VWF, indicating that the structure, orientation or the accessibility of the paratope is changed; while disulfide bonds were broken in the wild type and the monosubstituted mutants and dimers and multimers/higher aggregates were formed.

Conclusion: The results indicate that light induced excitation of W35(VL) and W36(VH) mediates photolysis of the vicinal disulfide bonds. And although the more distant W47(VH), W50(VH) and W108(VH) do not contribute to photolysis of the disulfide bonds, the simultaneous substitution of W35(VL) and of W36(VH) nevertheless did not protect the scFv’s affinity for VWF against illumination.

Open Access Original Research Article

Oxidative DNA Damage in Gestational Diabetes Mellitus: Correlation with Antioxidants in an Iraqi Cohort

Dina Jamil, Hayder Al-Aubaidy, Lachlan Smith, Herbert Jelinek

International Journal of Biochemistry Research & Review, Page 410-419
DOI: 10.9734/IJBCRR/2014/10138

Aims: This study aimed to evaluate the degree of oxidative stress in gestational diabetes mellitus when compared to non-diabetic pregnant women.

Methodology: This cross-sectional study included 73 participants (29 gestational diabetic women and 44 control pregnant women) attending the Maternal and Childhood Unit, Al-Husayniya Medical Centre, Baghdad, Iraq. The data was analyzed using SPSS (Version 14) and Microsoft Excel (Office2007, Microsoft). All values were expressed as mean±standard deviation (M±SD).

Results: Serum 8-Hydroxy-2-Deoxyguanosine was significantly (P < .001) greater in the gestational diabetes mellitus group compared to control group (57.2±17.6 ng/dl versus 19.8±7.8ng/dl respectively). The increase in 8-Hydroxy-2-Deoxyguanosine was associated with a significant (P < .001) elevation in serum malondialdehyde level (2.1±0.8 nmol/ml versus 1±0.4 nmol/ml) and a significant (P =.05) reduction in plasma reduced glutathione in the gestational diabetes mellitus group compared to the control group (20.6±5 mg/dl compared to 24.1±4.4 mg/dl). A significant change in total cholesterol (5.4±1.1mmol/L) and low density lipoprotein cholesterol (3.3±0.9mmol/L) were also noted in gestational diabetes mellitus group compared to the control group (4.7±1.3mmol/L and 2.8±1mmol/L respectively) at P =.05.

Conclusion: An increase in 8-Hydroxy-2-Deoxyguanosine is associated with higher levels of malondialdehyde and a significant reduction in reduced glutathione in gestational diabetes mellitus group, suggesting that significant oxidative stress associated with lipid peroxidation is occurring. Measuring these markers is useful in monitoring gestational diabetes mellitus to prevent the negative outcomes of gestational diabetes mellitus such as increased risk of diabetes and fetal morbidity.

Open Access Original Research Article

Histological Changes in Gonads and Liver of Oreochromis niloticus (L.) Fed Crude Extract of Azadirachta indica Leaf

I. O. Obaroh, G. C. Nzeh

International Journal of Biochemistry Research & Review, Page 420-429
DOI: 10.9734/IJBCRR/2014/7140

Structural changes in the gonads and liver of Oreochromis niloticus fed sub-lethal concentration of crude extract of Azadirachta indica leaf was investigated. The sub-lethal concentrations were earlier reported to inhibit reproduction in the fish species. Oreochromis niloticus of mean weight 29.30±2.02-31.79±3.11 were divided into 6 groups.  Each group was replicated three times. Fishes were stocked in out door concrete tanks (2x2x1.25 m) supplied with 450 litres of water. Six experimental diets (35% crude protein) containing varying sub-lethal concentrations of A. indica leaf crude extract (0.0, 0.5, 1.0, 2.0, 4.0 and 8.0 gkg-1 diets) were formulated (representing O, A, B, C, D and E respectively; O serves as the control). Fish were fed 3% body weight/day at two feeding instalments between 0900-0930 and 1700-1730 for 56 days. Ovary, testis and liver of fish fed control diet showed normal ovarian tissues, normal distribution of the testicular tissues and normal structure of the vein. Mild to severe necrosis and granulation of the interstitial tissue were observed in the ovaries as the concentration of the crude extract increased from 0.5 – 8.0 gkg-1. The testes showed mild to severe atrophy and cystic seminiferous tubules, while in the fish liver; increase in the number of rodlet cells and distortion of the vein walls were observed as the sub-lethal concentrations of the crude extract in the diets increased. Changes in the histology of the ovaries and testes showed the antiifertility potency of A. indica leaf, while changes in the liver histology revealed the sub-lethal toxicity effect of A. indica leaf all at moderate level of inclusions.

Open Access Original Research Article

Comparative Analysis of Cardio Metabolic Risk Factors in Context of Insulin Resistance among South Indian Obese and Non-obese Adolescents

Mahendra Bhauraoji Gandhe, Bhupendra Marotrao Gathe, Swapnali Mahendra Gandhe

International Journal of Biochemistry Research & Review, Page 430-439
DOI: 10.9734/IJBCRR/2014/10131

Background: Presently, it is of an utmost importance to know the prevalence of cardio metabolic risk factors and insulin resistance among obese adolescents in south Indian population, where genetic predisposition to obesity is high. This knowledge would enable us to take preventive measures as well as health education that can be implemented much early in school going adolescents.

Aim and Objectives: To study the prevalence of cardio metabolic risk factors in obese adolescent age group (11-18 years) and to correlate these cardio metabolic risk factors with insulin resistance among them.

Materials and Methods: A total of 120 adolescents (two groups: obese versus non-obese healthy controls) were selected for this cross-sectional study. Obesity was defined as per BMI at 95th percentile. Both groups were analysed for anthropometric parameters: body mass index (BMI), blood pressure (BP), waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR) and other relevant biochemical parameters viz. glucose (fasting), insulin (fasting), lipid profile and insulin resistance by Homeostasis model assessment of insulin resistance (HOMAIR). Statistical analysis was performed by Pearson’s correlation analysis using SPSS 16.0.

Results: The data depicts the prevalence of three or more than three cardio metabolic risk factors among obese adolescents (36.7%). BMI and WC were significantly higher among obese as compared to non-obese adolescents (P<0.001). Similarly, fasting glucose (P<0.05), insulin, insulin resistance (HOMAIR) were significantly increased among obese adolescents (P<0.001). Insulin resistance was having better correlation with BMI, WHR and mean arterial BP.

Conclusion: The result of the study clearly suggested a high prevalence of cardio metabolic risk factors among obese adolescents with elevation in insulin level and insulin resistance.

Open Access Original Research Article

Maternal Obesity and Malnutrition in Rats Differentially Affect Glucose Sensing in the Muscles and Adipose Tissues in the Offspring

Maher A. Kamel, Madiha H. Helmy, Mervat Y. Hanafi, Shimaa A. Mahmoud, Hanan Abo Elfetooh, Mahmoud S. Badr

International Journal of Biochemistry Research & Review, Page 440-469
DOI: 10.9734/IJBCRR/2014/10649

Background: The altered maternal/fetal metabolism appears to be associated with a diabetogenic effect in the adult offspring even in the absence of genetic predisposition.

Aim: The study aimed to investigate the effect of maternal obesity and malnutrition on the peripheral glucose sensing and mitochondria biogenesis in F1 offspring. Effect of postnatal diet was also evaluated.  

Methods: Three groups of female Wistar rats were used (control, obese and malnourished). After the pregnancy and delivery the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks.

Every 5 weeks OGTT was constructed and serum and tissues were obtained for assessment of glucose homeostasis parameters, mTFA, mtDNA, UCP2, insulin receptor (IR), phospho-insulin receptor (Phosho-IR) and GLUT4.

Results: The results indicated that maternal obesity impair glucose tolerance and sensing in the offspring from the 15th week of age even under control diet and the situation is worse under HCD these defects were preceded by significant decline in mtDNA copy number in muscle and adipose tissues as early as 5th week of age. The offspring of malnourished mothers show normal and even better glucose tolerance and sensing and normal mtDNA copy number under control diet, while those offspring under HCD show impaired glucose sensing and tolerance only at older age than obese group.   

Conclusion: maternal obesity and malnutrition differentially affect glucose sensing and tolerance, mtDNA copy number and the expression of genes involved in the mitochondrial biogenesis and function in the muscles and adipose tissues in the F1 offspring with the postnatal feeding appearing to play a central role in these differential effects. The male F1 offspring appear to be more sensitive for fetal diabetogenic programming than female offspring.