Rosuvastatin repurposing for prophylaxis against ethanol-induced acute gastric ulceration in rats: a biochemical, histological, and ultrastructural perspective.

Ethanol (EtOH) consumption is frequently associated with acute and chronic gastrointestinal disorders. Rosuvastatin (RSV), a third-generation statin, has demonstrated certain biological functions beyond its lipid-lowering properties. This study is designed to explore the gastroprotective impact of RSV in a rat model of EtOH-induced gastric ulceration in a dose-dependent manner through the evaluation of oxidant/antioxidant biomarkers, inflammatory myeloperoxidase (MPO) enzyme activity, and prostaglandin E2 (PGE2) levels in gastric tissues, along with histopathological examination of the gastric tissues. Therefore, 40 adult male rats were randomly divided into five equal groups as control, EtOH (gastric ulcer), RSV-low dose plus EtOH and RSV-high dose plus EtOH. The EtOH rat model of gastric ulceration was achieved by intragastric administration of a single dose of EtOH. Seven days before EtOH administration, rats were orally administered either omeprazole (20 mg/kg/day) or RSV (10 mg/kg/day or 20 mg/kg/day). RSV administration enhanced the antioxidant glutathione reduced, countered oxidative malondialdehyde, augmented cytoprotective PGE2, suppressed inflammatory MPO enzyme activity in gastric tissues, decreased ulcer index scoring, increased the percentage of ulcer inhibition, and reversed the associated histological and ultrastructural abnormalities, additionally, RSV treatment resulted in weak positive nuclear staining for the inflammatory nuclear factor kappa B in a dose-dependent manner. It is concluded that RSV demonstrates gastroprotective potential, attributable at least in part, to its antioxidant and anti-inflammatory properties, as well as its ability to promote ulcer protection through the maintenance of mucosal content and PGE2 levels. Thus, RSV therapy emerges as a safe option for patients with gastric ulcers.

Modulation of the Sirtuin-1 signaling pathway in doxorubicin-induced nephrotoxicity (synergistic amelioration by resveratrol and pirfenidone).

The current study was conducted to determine the precise mechanisms of Sirtuin-1 (Sirt-1), TGF- ß (Transforming Growth Factor-ß), and long non-coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (LncRNA MALAT-1) in signaling pathways in doxorubicin (DOX)-induced nephrotoxicity. The potential therapeutic effect of Resveratrol and Pirfenidone in DOX toxicity was also assessed. Thirty-six male adult rats were evenly distributed into four groups: Group 1: control rats. Group 2: DOX exposed rats' group, each animal received 7.5 mg/kg DOX as a single intravenous dose, Group 3: DOX exposed group subjected to oral resveratrol (20 mg/kg/daily for two weeks), Group 4: DOX exposed group subjected to oral Pirfenidone (200 mg/kg once daily for 10 days). At the planned time, animals were sacrificed. Renal tissue was collected to assess matrix metalloproteinase-9 (MMP9), inflammatory and apoptotic markers: tumor necrosis factor-alpha (TNF- ß, caspase-3, cyclo-oxygenase-2 (COX-2), and oxidative stress markers: nitric oxide (NO), Glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD). Sirtuin-1 (Sirt-1), TGF-ß, and LncRNA MALAT-1 were quantitatively assessed by real-time RT-PCR in the whole blood. Results showed that the DOX group exhibited a significant increase in oxidative stress markers, and inflammatory, and apoptotic markers in the renal tissue. Histologically, the renal tubule lining cells exhibited vacuolar alterations in the cytoplasm, glomerular atrophy, and vascular congestion. Furthermore, renal degeneration was evident, as confirmed by the heightened immuno-expression of MMP9. Exposure to DOX resulted in a significant decrease in Sirtuin-1 (Sirt-1) with a significant increase in the TGFß, and LncRNA MALAT-1 gene expression. However, pre-treatment with either resveratrol/or Pirefenidone ameliorated the histological renal alterations, regulated the pathways of Sirt-1, TGFß, and LncRNA MALAT-1, and decreased all oxidative stress, inflammatory and apoptotic markers. In conclusion, DOX exposure leads to renal toxicity by inducing renal degeneration, oxidative stress, and apoptosis. Administration of either resveratrol or Pirfenidone counteracted these changes and protected the kidney against DOX-induced renal damage.

Role of the renin-angiotensin system in the pathophysiology of coronary heart disease and heart failure: Diagnostic biomarkers and therapy with drugs and natural products.

The renin-angiotensin system (RAS) plays a pivotal role in blood pressure regulation. In some cases, this steering mechanism is affected by various deleterious factors (mainly via the overactivation of the RAS) causing cardiovascular damage, including coronary heart disease (CHD) that can ultimately lead to chronic heart failure (CHF). This not only causes cardiovascular disability and absenteeism from work but also imposes significant healthcare costs globally. The incidence of cardiovascular diseases has escalated exponentially over the years with the major outcome in the form of CHD, stroke, and CHF. The involvement of the RAS in various diseases has been extensively researched with significant limelight on CHD. The RAS may trigger a cascade of events that lead to atherosclerotic mayhem, which causes CHD and related aggravation by damaging the endothelial lining of blood vessels via various inflammatory and oxidative stress pathways. Although there are various diagnostic tests and treatments available in the market, there is a constant need for the development of procedures and therapeutic strategies that increase patient compliance and reduce the associated side effects. This review highlights the advances in the diagnostic and treatment domains for CHD, which would help in subjugating the side effects caused by conventional therapy.

Network-Based Approach and IVI Methodologies, a Combined Data Investigation Identified Probable Key Genes in Cardiovascular Disease and Chronic Kidney Disease.

In fact, the risk of dying from CVD is significant when compared to the risk of developing end-stage renal disease (ESRD). Moreover, patients with severe CKD are often excluded from randomized controlled trials, making evidence-based therapy of comorbidities like CVD complicated. Thus, the goal of this study was to use an integrated bioinformatics approach to not only uncover Differentially Expressed Genes (DEGs), their associated functions, and pathways but also give a glimpse of how these two conditions are related at the molecular level. We started with GEO2R/R program (version 3.6.3, 64 bit) to get DEGs by comparing gene expression microarray data from CVD and CKD. Thereafter, the online STRING version 11.1 program was used to look for any correlations between all these common and/or overlapping DEGs, and the results were visualized using Cytoscape (version 3.8.0). Further, we used MCODE, a cytoscape plugin, and identified a total of 15 modules/clusters of the primary network. Interestingly, 10 of these modules contained our genes of interest (key genes). Out of these 10 modules that consist of 19 key genes (11 downregulated and 8 up-regulated), Module 1 (RPL13, RPLP0, RPS24, and RPS2) and module 5 (MYC, COX7B, and SOCS3) had the highest number of these genes. Then we used ClueGO to add a layer of GO terms with pathways to get a functionally ordered network. Finally, to identify the most influential nodes, we employed a novel technique called Integrated Value of Influence (IVI) by combining the network's most critical topological attributes. This method suggests that the nodes with many connections (calculated by hubness score) and high spreading potential (the spreader nodes are intended to have the most impact on the information flow in the network) are the most influential or essential nodes in a network. Thus, based on IVI values, hubness score, and spreading score, top 20 nodes were extracted, in which RPS27A non-seed gene and RPS2, a seed gene, came out to be the important node in the network.