Grape seed proanthocyanidins (GSPE) and ginkgo biloba extract (EGb761) are considered to have protective effects against several diseases. The cardiotoxicity of doxorubicin (DOX) has been reported to be associated with oxidative damage. This study was conducted to evaluate the cardioprotective effects of GSPE and EGb761 against DOX-induced heart injury in rats. DOX was administered as a single i.p. dose (20 mg kg(-1)) to adult male rats. DOX-intoxicated rats were orally administered GSPE (200 mg kg(-1)  day(-1)) or EGb761 (100 mg kg(-1)  day(-1)) for 15 consecutive days, starting 10 days prior DOX injection. DOX-induced cardiotoxicity was evidenced by a significant increase in serum aspartate transaminase (AST), creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), total cholesterol (TC) and triglyceride (TG) activities and levels. Increased oxidative damage was expressed by the depletion of cardiac reduced glutathione (GSH), elevation of cardiac total antioxidant (TAO) level and accumulation of the lipid peroxidation product, malondialdehyde (MDA). Significant rises in cardiac tumour necrosis factor-alpha (TNF-α) and caspase-3 levels were noticed in DOX-intoxicated rats. These changes were ameliorated in the GSPE and EGb761-treated groups. Histopathological analysis confirmed the cardioprotective effects of GSPE and EGb761. In conclusion, GSPE and EGb761 mediate their protective effect against DOX-induced cardiac injury through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. The pathogenesis of DPN is complex and involves an intertwined array of mechanisms. The purposes of this study were to evaluate the association of oxidative stress and vascular risk factors with the prevalence of DPN and to determine the role of these biochemical parameters in the prognosis of DPN. One hundred patients with type 2 diabetes mellitus and 40 clinically healthy individuals were evaluated. The patients were divided into two groups. Group 1 included 40 diabetic patients without peripheral neuropathy, and group 2 consisted of 60 patients with DPN. Erythrocytes glutathione (GSH) level, plasma malondialdehyde (MDA), nitrite/nitrate (NOx) and homocysteine (Hcy) levels as well as serum ceruloplasmin (Cp), total antioxidants (TAO), endothelin-1 (ET-1) levels and γ-glutamyl transferase (GGT) activity were estimated. A significant decrease of erythrocyte GSH was observed in groups 1 and 2 relative to the controls. An increase in glycosylated haemoglobin (HbA1c), MDA, NOx, GGT, Cp, TAO, Hcy and ET-1 was noted in patients with DPN. In conclusion, oxidative stress biomarkers and vascular risk factors could be important in the pathogenesis of DPN. The measurement of serum GGT and Hcy in addition to HbA1c and disease duration could facilitate the early detection of neuropathy in diabetic patients.

Paraquat (PQ) is one of the most used herbicide worldwide. Its cytotoxicity is attributed to reactive radical generation. Resveratrol (Res) and montelukast (MK) have anti-inflammatory and antioxidant properties. The protective effects of Res, MK, or their combination against PQ-induced acute liver injury have not been investigated before. Therefore, we explored the protective potential of Res and/or MK against PQ hepatic toxicity in a mouse model. Mice were randomly assigned to five groups: group I served as the normal control and group II received a single dose of PQ (50 mg/kg, i.p.). Groups III, IV, and V received PQ plus oral Res (5 mg/kg/day), MK (10 mg/kg/day), and Res/MK combination, respectively. Res and/or MK reduced PQ-induced liver injury, evidenced by normalization of serum total protein, ALT, and AST. Res and/or MK significantly reversed PQ-induced oxidative stress markers glutathione and malondialdehyde. Res and/or MK significantly reduced PQ-induced inflammation reflected in TNF-α levels. Furthermore, Res and/or MK reversed PQ-induced apoptosis assessed by differential expression of p53, Bax, and Bcl-2. Histopathologic examination supported the biochemical findings. Although Res and MK displayed antioxidative, anti-inflammatory, and antiapoptotic activities, their combination was not always synergistic.

This study investigated the effect of curcumin against diethylnitrosamine (DEN)‐induced hepatocarcinogenesis. Rats were divided into three groups. The first group served as a control. The second group received DEN (orally, 20 mg/kg) five times a week for 8 weeks, followed by 10 mg/kg for another 7 weeks. The third group was supplemented with 2% curcumin diet simultaneously with DEN. The results showed normalization of serum level of total antioxidant capacity, γ‐glutamyl transferase and aminotransferase activities along with deoxyribonucleic acid, ribonucleic acid and malondialdehyde levels, glutathione reductase and glutathione peroxidase activities in the liver of curcumin group. Significant decreases in the elevated level of glutathione, glutathione‐S‐transferase and glucose‐6‐P dehydrogenase activities were observed. Serum alkaline phosphatase activity and the relative liver weight were not significantly altered. Concomitantly, the histopathological damage was attenuated by curcumin. In conclusion, curcumin exerted a potential chemopreventive effect in DEN‐induced hepatocarcinogenesis. PRACTICAL APPLICATIONS Various therapeutic effects, such as anti‐inflammatory, anti‐cancer, anti‐angiogenic and wound‐healing effects, have been described for curcumin. The present study is an endeavor in the direction of determining its possible mechanism of protection in diethylnitrosamine‐induced hepatocarcinogenesis in rats. Our study proved that curcumin exhibits a hepatoprotective potential, and hence, it can be used as value‐added agents to limit both exposure to and the adverse health effects from dietary hepatocarcinogens.

The influence of PVT1 and MALAT1 variants on colorectal cancer (CRC) susceptibility and their impact on PVT1/miRNA-186/epithelial-mesenchymal transition (EMT) and MALAT1/miRNA-101/EMT axes in CRC are unknown. We investigated the influence of PVT1 rs13255292 and MALAT1 rs3200401 on the risk of CRC and adenomatous polyps (AP), their impact on the long noncoding RNAs PVT1 and MALAT1 expression and their target miRNA-186, miRNA-101/E-cadherin pathways, along with their potential as early CRC biomarkers. Overall, 280 individuals were recruited: 140 patients with CRC, 40 patients with AP, and 100 healthy volunteers. Genotyping and serum expression profiles were assessed using qPCR. The EMT biomarker, E-cadherin, was measured by ELISA. rs3200401 was associated with increased CRC risk, whereas rs13255292 was protective. Serum PVT1 and MALAT1 were upregulated in CRC and AP patients versus healthy controls, whereas, miRNA-186, miRNA-101 and E-cadherin were downregulated in CRC versus non-CRC groups. MALAT1 showed superior diagnostic potential for CRC and predicted CRC risk among non-CRC groups in the multivariate logistic analysis. PVT1, MALAT1, miRNA-186 and miRNA-101 levels were correlated with E-cadherin, tumor stage, lymph node and distant metastasis. E-cadherin was lost in metastatic vs. non-metastatic CRC. rs3200401CC genotype carriers showed higher E-cadherin levels than CC + CT carriers. rs3200401 was correlated with lymph node status. For the first time, rs13255292 and rs3200401 are potential genetic CRC predisposition markers, with rs3200401 possibly impacting the EMT process. Serum PVT1, MALAT1, miRNA-186 and miRNA-101 are novel non-invasive diagnostic biomarkers that could improve the clinical outcome of CRC.