Azilsartan Modulates HMGB1/NF-κB/p38/ERK1/2/JNK and Apoptosis Pathways during Renal Ischemia Reperfusion Injury.

Renal ischemia/reperfusion (IR) injury is characterized by an unexpected impairment of blood flow to the kidney. Azilsartan is an angiotensin receptor blocker that is approved for the management of hypertension. The present study aimed to investigate, on molecular basics, the nephroprotective activity of azilsartan on renal IR injury in rats. Rats were assigned into four groups: (1) Sham group, (2) Azilsartan group, (3) IR group, and (4) IR/Azilsartan-treated group. Histological examination and renal function were evaluated. Levels of KIM-1, HMGB1, caspase 3, GPX, SOD, NF-κB, and p53 proteins were investigated using ELISA. mRNA levels of IL-1ß, IL6, IL10, TNF-α, NF-κB, p53, and bax were assessed by qRT-PCR. Expression of p38, JNK, and ERK1/2 proteins was investigated by Western blotting. IR injury resulted in tissue damage, elevation of creatinine, BUN, KIM-1, HMGB1, caspase 3, NF-κB, and p53 levels, decreasing GPX and SOD activities, and up-regulation of NF-κB, IL-1ß, IL6, TNF-α, p53, and bax genes. Furthermore, it up-regulated the expression of phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Interestingly, treatment of the injured rats with azilsartan significantly alleviated IR injury-induced histopathological and biochemical changes. It reduced the creatinine, BUN, KIM-1, HMGB1, caspase-3, NF-κB, and p53 levels, elevated GPX and SOD activities, down-regulated the expression of NF-κB, IL-1ß, IL6, TNF-α, p53, and bax genes, and up-regulated IL10 gene expression. Furthermore, it decreased the phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Azilsartan exhibited nephroprotective activity in IR-injured rats via its antioxidant effect, suppression of inflammation, attenuation of apoptosis, and inhibition of HMGB1/NF-κB/p38/ERK1/2/JNK signaling pathway.

Pantoprazole Attenuates MAPK (ERK1/2, JNK, p38)-NF-κB and Apoptosis Signaling Pathways after Renal Ischemia/Reperfusion Injury in Rats.

Ischemia/reperfusion injury (IRI) in the kidney is the most common cause of acute renal dysfunction through different cell damage mechanisms. This study aimed to investigate, on molecular basics for the first time, the effect of pantoprazole on renal IRI in rats. Different biochemical parameters and oxidative stress markers were assessed. ELISA was used to estimate proinflammatory cytokines. qRT-PCR and western blot were used to investigate the gene and protein expression. Renal histopathological examination was also performed. IRI resulted in tissue damage, elevation of serum levels of creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, IL-1ß, up-regulation of NF-κB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it up-regulated the expression of the Bax gene and down-regulated the expression of the Bcl-2 gene. Treatment of the injured rats with pantoprazole, either single dose or multiple doses, significantly alleviated IRI-induced biochemical and histopathological changes, attenuated the levels of proinflammatory cytokines, down-regulated the expression of NF-κB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins, and the Bax gene, and up-regulated Bcl-2 gene expression. Moreover, treatment with pantoprazole multiple doses has an ameliorative effect that is greater than pantoprazole single-dose. In conclusion, pantoprazole diminished renal IRI via suppression of apoptosis, attenuation of the pro-inflammatory cytokines' levels, and inhibition of the intracellular signaling pathway MAPK (ERK1/2, JNK, p38)-NF-κB.

The adipokine Chemerin and Fetuin-A Serum Levels in Type 2 Diabetes Mellitus: Relation to Obesity and Inflammatory Markers.

Chemerin and fetuin-A are recently discovered as metabolic regulator hormone in obesity and type 2 diabetes mellitus. However, elevated levels of chemerin and fetuin-A have been associated with insulin resistance and systemic inflammation. The present study aimed to investigate the significance of serum chemerin and fetuin-A levels in obese diabetic patients. Also, to determine whether, chemerin and fetuin-A along with markers of inflammation (IL6 and CRP) and obesity-related parameters in T2DM patients. Serum levels of chemerin and fetuin-A were evaluated using ELISA in 71 T2DM patients and 14 apparently healthy controls. Both groups were subdivided into obese and lean. Serum chemerin and fetuin-A levels were significantly higher in T2DM patients compared to controls (P < 0.001, for both) and significantly higher in obese T2DM in comparison to obese control group (P < 0.01 & P < 0.05, respectively). Serum chemerin and fetuin-A levels correlated positively with HbA1c, HOMA-IR, FBG, IL6 and CRP. In obese patients, serum chemerin and fetuin-A levels correlated positively with BMI and waist circumference. In conclusion, the strong association of chemerin and fetuin-A with insulin resistance and some inflammatory markers may provide an interesting link between obesity, inflammation and diabetes mellitus in human.

Latent tuberculosis infection among patients with coronary artery stenosis: A case-Control study.

Background: The activation of the cell-mediated immune responses by Mycobacterium tuberculosis can promote atherogenesis. Aims: The aim of this study is to determine the frequency of latent tuberculosis infection (LTBI) among patients with coronary artery stenosis (CAS) and to explore the association between LTBI and development of CAS. We conducted a case-control study which included 183 patients' who underwent percutaneous coronary angiography (121 patients with CAS and 62 patients without as a control group). Methods: For all the study population, clinical evaluation, tuberculin skin test (TST), imaging studies (including chest radiography and echocardiography), laboratory investigations, and electrocardiography were carried out. Only for the patients with positive TST, QuantiFERON-TB Gold test was performed. Predictors of CAS were identified using univariate analyses (Yates' corrected Chi-square test or Fischer's exact test) followed by multivariate analysis (binary logistic regression). Results: Among 29.5% of the study population, LTBI was detected, and among patients with CAS, 56.2% of patients had advanced CAS. After multivariate analysis, it was found that metabolic syndrome (MS) (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.5-22.6, P = 0.022) and LTBI (OR 2.5, 95% CI 1.2-17.3, P = 0.018) were the predictors of CAS among the study population, while only diabetes mellitus (DM) (OR 1.9, 95% CI 1.1-11.7, P = 0.031) was the predictor of advanced CAS. Conclusion: LTBI is associated with the development of CAS. In addition, MS is associated with CAS, while its related disorder, DM, is associated with advanced CAS.

Latent tuberculosis infection among patients with erectile dysfunction.

No previous studies have investigated the prevalence of latent tuberculosis infection (LTBI) among patients with erectile dysfunction (ED) or its contribution to the development of high-grade ED through a process of chronic inflammation-induced atherosclerosis. The aim of this study was to determine the frequency of LTBI among patients with erectile dysfunction and to explore the contribution of LTBI to high-grade ED. For all the study sample, clinical evaluation, imaging studies, and laboratory investigations were provided. Evaluation included, but was not confined to, scrotal ultrasonography, tuberculin skin test, and QuantiFERON-TB Gold test. The study sample mean ± SD age was 47.9 ± 13.6 years. Approximately 30% of the patients had LTBI and 43% had high-grade ED. After a multivariate analysis, it was found that older age (≥40 years) (OR, 5.2; 95% CI, 1.9-54.6; p 0.004), metabolic syndrome (MS) (OR, 3.4; 95% CI, 1.3-48.2; p 0.016), and LTBI (OR, 4.1; 95% CI, 1.7-61.3; p 0.021) were significantly, independently associated with high-grade ED as opposed to low-grade ED. In conclusion, the prevalence of LTBI among patients with high-grade ED is higher than among those with low-grade ED. In addition to LTBI, older age and MS are associated with high-grade ED as opposed to low-grade ED.