Inflammatory Bowel Disease: The Association of Inflammatory Cytokine Gene Polymorphisms

The frequencies of alleles and genotypes of TNF-α, TNF-β, and IL-10 genes were examined in Saudi subjects including IBD patients (UC and CD) and matched controls. Venous blood samples were collected from IBD patients and healthy control subjects, and genomic DNA was extracted using commercially available kit (Qiagen, CA, USA). In order to detect TNF-α (-308G/A), TNF-β (+252A/G), IL-10 (-1082G/A), (-819C/T), and (-592C/A) polymorphisms, the TNF-α, TNF-β, and IL-10 genes were amplified using an amplification refractory mutation systems PCR methodology. Analysis of data showed that the frequencies of alleles and genotype of TNF-α (-308G/A), TNF-β (+252A/G), and IL-10 (-1082G/A), (-819C/T), and (-592C/A) polymorphisms differ between IBD patients and control subjects. Our study clearly indicated that the TNF-α (-308G/A), TNF-β (+252A/G), and IL-10 (-1082 G/A) polymorphisms are associated significantly with the risk of IBD susceptibility while other two, IL-10-819C/T and IL-10-592C/A, polymorphisms are not associated with IBD in Saudi population. However, well-designed epidemiological as well as genetic association studies with large sample size among different ethnicities should be performed in order to have better understanding of this relationship

Camel Milk Beneficial Effects on Treating Gentamicin Induced Alterations in Rats

The potential effect of camel milk (CM) against gentamicin (GM) induced biochemical changes in the rat serum was evaluated. Four groups of six albino rats were used for control, CM fed, injected with GM(i.p.), and then fed and injected with GM. The results showed that the administration of GM significantly altered the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activity in rat serum. CM restored these parameters to almost their normal range in group IV. Additionally, the present study showed that injection of rats with gentamicin caused an increase in malondialdehyde (MDA) and myeloperoxidase (MPO) activity while the antioxidant enzymes like superoxide dismutase (SOD) and glutathione s-transferase (GST) activity decreased significantly (P≤0.05). Administration of CM significantly (P≤0.05) inhibited the formation of MDA and activity of MPO and upregulated the antioxidant enzymes (SOD and GST) activity. The overall findings of this study demonstrated that pretreatment with CM gave protection against GM induced hepatic damage possibly by inhibiting oxidative stress and inflammation, and hence camel milk can be identified as a new therapeutic agent

The effect of ascorbic acid on Bitis arietans venom induced toxicity in rats

Ascorbic acid (AsAc) was tested to evaluate its ability to reverse the oxidative stress induced by envenoming. Test groups of rats were envenomed with sub-lethal doses (4.0 mg/kg s.c.) of Bitis arietans venom (BaV) whilst, single doses (500 mg/kg, orally) of AsAc were pre-administered in half of them. Blood samples were collected within three periods and levels of lipid peroxidation (LPO) and total-SH increased significantly, whilst, the ‘Venom + AsAc’ groups were significantly less than both, the respective ‘Venom’ groups and controls, at different periods. The antioxidant, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzyme level changes were trivial at the three periods, whilst, there were no changes in the ‘Venom + AsAc’ groups, compared with controls, except SOD which, became significant after 24 h. SCr and BUN levels were significantly higher than the controls within the three periods with variable degrees, whilst, the ‘Venom + AsAc’ group level changes were insignificant compared with controls and their respective ‘Venom’ groups at all periods. Blood urea Nitrogen (BUN), became significantly lower after 24 h. After 6 and 24 h AST levels were significantly higher than controls, whilst, ALT was not. Level changes of both AST and ALT ‘Venom + AsAc’ groups were insignificant, compared with controls at all periods. It is concluded that oxidative stress due to envenoming by BaV induced variable levels of significant changes in levels of nephrotoxic, hepatotoxic markers and antioxidant enzyme parameters. Administration of AsAc relatively adjusted these changes with different degrees, at variable periods of time that demands further deeper research in beneficiary mechanisms of antioxidants

Simvastatin Attenuates Contrast-Induced Nephropathy through Modulation of Oxidative Stress, Proinflammatory Myeloperoxidase, and Nitric Oxide

Contrast media- (CM-) induced nephropathy is a serious complication of radiodiagnostic procedures. Available data suggests that the development of prophylaxis strategies is limited by poor understanding of pathophysiology of CM-induced nephropathy. Present study was designed to determine the role of oxidative stress, myeloperoxidase, and nitric oxide in the pathogenesis of iohexol model of nephropathy and its modification with simvastatin (SSTN). Adult Sprague Dawley rats were divided into seven groups. After 24 h of water deprivation, all the rats except in control and SSTN-only groups were injected (10 ml/kg) with 25% glycerol. After 30 min, SSTN (15, 30, and 60 mg/kg) was administered orally, daily for 4 days. Twenty-four hours after the glycerol injection, iohexol was infused (8 ml/kg) through femoral vein over a period of 2 min. All the animals were sacrificed on day 5 and blood and kidneys were collected for biochemical and histological studies. The results showed that SSTN dose dependently attenuated CM-induced rise of creatinine, urea, and structural abnormalities suggesting its nephroprotective effect. A significant increase in oxidative stress (increased lipid hydroperoxides and reduced glutathione levels) and myeloperoxidase (MPO) and decreased nitric oxide in CM group were reversed by SSTN. These findings support the use of SSTN to combat CM-induced nephrotoxicity

Association of glutathione S-transferase and deletion polymorphisms with obesity and their relationship with body mass index, lipoprotein and hypertension among young age Saudis

Objectives Persistent oxidative stress is one of the several risk factors that may be associated with the etiology of obesity. The present study is aimed to investigate association between GSTM1 and GSTT1 polymorphisms with obesity and their relationship with plasma lipoproteins, body mass index (BMI) and hypertension. Design The GSTM1 and GSTT1 deletion polymorphisms were analyzed by multiplex polymerase chain reaction. The lipoproteins were measured in plasma using commercially available kit and the weight, height, systolic (SBP) and diastolic (DBP) blood pressures by standard procedure of measurements. Setting Prince Sultan Military Medical City, Riyadh Saudi Arabia. Participants A total of 420 overweight/obese cases and 234 normal weight controls belong to young age Saudis. Main outcomes measures GSTM1 / GSTT1 polymorphisms may be associated with obesity. Results Weight, BMI, low-density lipoprotein (LDL) and SBP were significantly higher while high-density lipoprotein (HDL) was significantly lower in cases in comparison to controls. Frequency of GSTM1 +/ GSTT1 − (OR = 2.70, 95% CI = 1.52–4.81, p  = <0.001) and GSTM1 −/ GSTT1 − (OR = 2.43, 95% CI = 1.15–5.15, p  = 0.018) was significantly higher in cases as compared to controls. BMI and weight were significantly higher in GSTM1 +/ GSTT1 − and GSTM1 −/ GSTT1 − genotypes, and LDL, DBP and SBP significantly higher in GSTM1 −/ GSTT1 − null genotype while HDL was significantly lower in GSTM1 −/ GSTT1 + and GSTM1 −/ GSTT1 − genotypes in comparison to GSTM1 +/ GSTT1 + genotype. Conclusions The GSTM1 +/ GSTT1 − and GSTM1 −/ GSTT1 − null genotypes were significantly associated with obesity and have shown relationship with obesity risk factors in cases. Hence, these genes may be associative genetic risk factor for obesity among young age Saudis

Serum Levels of Proinflammatory Biomarkers in Military Recruits with and without Metabolic Syndrome

Objectives. Inflammatory mediators are associated with many chronic diseases; however, their role in metabolic syndrome (Met-S) is not well documented. We therefore aimed to compare the serum markers of inflammation including C-reactive protein (CRP), myeloperoxidase (MPO), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), and TNF-β in young military recruits with and without Met-S. We hypothesized that any significant change in inflammatory markers between the two groups would indicate the role of inflammation in Met-S that would help in future directions for screening and treatment of Met-S. Design and Methods. A total of 2010 adult men, aged 18-30 years, were divided into two groups: with Met-S (N=488) and without Met-S (N=1522), according to the International Diabetes Federation definition. We compared the serum levels of inflammatory biomarkers between the two groups. We also studied the correlations between the inflammatory markers and the components of Met-S to explore the biomarker potential of inflammatory markers for screening of Met-S. Logistic regression analysis was performed to test the association between inflammatory markers and Met-S. Results. A large number of subjects in the Met-S group were suffering from obesity. Out of the 2010 total subjects, only 731 (36.4%) had normal fasting blood sugar (FBS), while the prevalence of prediabetes and diabetes was significantly higher in subjects with Met-S. We observed significant increases in serum levels of CRP, MPO, IL-6, and TNF-β but not TNF-α in subjects with Met-S as compared to subjects without Met-S. All the markers of inflammation showed significant correlations with Met-S, triglycerides (TG), blood pressure, body mass index (BMI), and age; however, none of these markers were correlated with HDL. Logistic regression analysis showed a significant association between Met-S and inflammatory markers. Conclusions. Serum levels of CRP, MPO, IL-6, and TNF-β are significantly increased in young adults with Met-S. This is probably the first study reporting TNF-β levels in Met-S. Since a proinflammatory cascade precedes many years before the onset of cardiovascular disease, these inflammatory biomarkers could help in the monitoring of high-risk individuals with Met-S who will be requiring therapeutic intervention

The association of metformin use with vitamin B12 deficiency and peripheral neuropathy in Saudi individuals with type 2 diabetes mellitus.

AIMS:To compare the prevalence of vitamin B12 deficiency and peripheral neuropathy between two groups of type 2 diabetes mellitus (T2DM) patients treated with or without metformin, and to determine factors associated with vitamin B12 deficiency therapy and dietary intake of vitamin B12. METHODS:In this retrospective study, we recruited 412 individuals with T2DM: 319 taking metformin, and 93 non-metformin users. Demographics, dietary assessment for vitamin B12 intakes, and medical history were collected. Participants were assessed for peripheral neuropathy. Blood specimens were collected and checked for serum vitamin B12 levels. The differences between the two groups were analyzed using an independent t-test for continuous data, and the Chi-squared or Fisher's exact test was used for categorical data. The relationship of vitamin B12 deficiency with demographics and clinical characteristics was modeled using logistic regression. RESULTS:The prevalence of B12 deficiency was 7.8% overall, but 9.4% and 2.2% in metformin users and non-metformin users, respectively. The odds ratio for serum vitamin B12 deficiency in metformin users was 4.72 (95% CI, 1.11-20.15, P = 0.036). There were no significant differences in a test of peripheral neuropathy between the metformin users and non-metformin users (P > 0.05). Low levels of vitamin B12 occurred when metformin was taken at a dose of more than 2,000 mg/day (AOR, 21.67; 95% CI, 2.87-163.47) or for more than 4 years (AOR, 6.35; 95% CI, 1.47-24.47). CONCLUSION:Individuals with T2DM treated with metformin, particularly those who use metformin at large dosages (> 2,000 mg/day) and for a longer duration (> 4 years), should be regularly screened for vitamin B12 deficiency and metformin is associated with B12 deficiency, but this is not associated with peripheral neuropathy