Doxorubicin (DOX) is a cytotoxic anthracycline antibiotic and one of the important chemotherapeutic agents for different types of cancers. DOX treatment is associated with adverse effects, particularly cardiac dysfunction. This study examined the cardioprotective effects of carvedilol (CAR) and/or resveratrol (RES) and liposomal RES (LIPO-RES) against DOX-induced cardiomyopathy, pointing to their modulatory effect on oxidative stress, inflammation, S100A1 and sarco/endoplasmic reticulum calcium ATPase2a (SERCA2a). Rats received CAR (30 mg/kg) and/or RES (20 mg/kg) or LIPO-RES (20 mg/kg) for 6 weeks and were challenged with DOX (2 mg/kg) twice per week from week 2 to week 6. DOX-administered rats exhibited a significant increase in serum creatine kinase-MB (CK-MB), troponin-I and lactate dehydrogenase (LDH) along with histological alterations, reflecting cardiac cell injury. Cardiac toll-like receptor 4 (TLR-4), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α and interleukin (IL)-6 protein expression were up-regulated, and lipid peroxidation was increased in DOX-administered rats. Treatment with CAR, RES or LIPO-RES as well as their alternative combinations ameliorated all observed biochemical and histological alterations with the most potent effect exerted by CAR/LIPO-RES. All treatments increased cardiac antioxidants, and the expression of S100A1 and SERCA2a. In conclusion, the present study conferred new evidence on the protective effects of CAR and its combination with either RES or LIPO-RES on DOX-induced inflammation, oxidative stress and calcium dysregulation.
Background:Lead is a common environmental and occupational pollutant which induced
multiorgans dysfunction. The present study was designed to investigate the
hepatoprotective effects of turmeric (TUR) and/or vitamin C (Vit-C) alone or
together against lead acetate toxicity and to explore novel molecular
pathways.Method:Acute hepatotoxicity was induced by lead acetate (100 mg/kg/day, i.p.) in
male rats, and the effect of TUR (200 mg/kg/day, orally) and/or Vit-C (250
mg/kg/day, orally) along with lead acetate for 7 days was studied.Results:Lead acetate increased serum alanine transaminase, aspartate transaminase,
lactate dehydrogenase, hepatic lipid peroxidation and nitric oxide; while,
hepatic superoxide dismutase and glutathione activities were downregulated.
Hepatic Bcl-2-associated X (Bax) and B-cell lymphoma-2 (Bcl-2) proteins
expressions were altered and hepatic DNA damaged was increased as well.
Liver/body weight ratio was decreased. Hematoxylin and eosin demonstrated
that lead acetate induced focal areas of massive hepatic degeneration of the
hepatocytes. Treatment with both antioxidants ameliorated all the altered
parameters and induced marked improvement of liver architecture.Conclusion:The combination of TUR and Vit-C has shown the most protective effects
against lead acetate-induced hepatotoxicity.
The use of the cytotoxic antibiotic doxorubicin (DOXR) is limited by its dose‐dependent cardiotoxicity. The aim of this study was to evaluate the cardioprotective effect of the combination of carvedilol (CARD) and liposomal resveratrol (LIPO RESV) against DOXR‐induced cardiomyopathy in rats. The results of the present study showed that DOXR administration significantly increased heart weight/body weight ratio by 35.6%, creatine kinase‐MB (CK‐MB) by 40.6%, troponin‐I levels by 85%, and decreased reduced glutathione level and superoxide dismutase activity by 47% and 52%, respectively compared to the control group. Moreover, cardiac caspase‐3 protein expression was upregulated by 51.6% vs the control group. In contrast, treatment of DOXR‐administered rats with CARD, RESV, or LIPO RESV and their combination for 6 weeks improved all the above‐mentioned measured parameters. In conclusion, concomitant administration of CARD and LIPO RESV exerted additive pharmacological effects in some measured parameters against DOXR‐induced cardiomyopathy and this may be a useful cardioprotective strategy.
Background: Although doxorubicin (DXR) is one of the most used anticancer drugs, it can cause life-threatening renal damage. There has been no effective treatment for DXR-induced renal damage until now.Aim: This work aims at examining the potential impact of nano-resveratrol (N-Resv), native resveratrol (Resv), and their combination with carvedilol (Card) against DXR-induced renal toxicity in rats and to investigate the mechanisms through which these antioxidants act to ameliorate DXR nephrotoxicity. Method: DXR was administered to rats (2 mg/kg, i.p.) twice weekly over 5 weeks. The antioxidants in question were taken 1 week before the DXR dose for 6 weeks.Results: DXR exhibited an elevation in serum urea, creatinine, renal lipid peroxide levels, endoglin expression, kidney injury molecule-1 (KIM-1), and beclin-1. On the other hand, renal podocin and mTOR expression and GSH levels were declined. In addition, DNA fragmentation was markedly increased in the DXR-administered group. Treatment with either Resv or N-Resv alone or in combination with Card ameliorated the previously measured parameters.Conclusion: N-Resv showed superior effectiveness relative to Resv in most of the measured parameters. Histopathological examination revealed amelioration of renal structural and cellular changes after DXR by Card and N-Resv, thus validating the previous biochemical and molecular results.
The advancement in therapy has provided a dramatic improvement in the rate of recovery among cancer patients. However, this improved survival is also associated with enhanced risks for cardiovascular manifestations, including hypertension, arrhythmias, and heart failure. The cardiotoxicity induced by chemotherapy is a life-threatening consequence that restricts the use of several chemotherapy drugs in clinical practice. This article addresses the prevalence of cardiotoxicity mediated by commonly used chemotherapeutic and immunotherapeutic agents. The role of susceptible genes and radiation therapy in the occurrence of cardiotoxicity is also reviewed. This review also emphasizes the protective role of antioxidants and future perspectives in anticancer drug-induced cardiotoxicities.
Introduction: One of the most common non motor symptoms of Parkinson's disease (PD) is cognitive decline. Scientific evidence has demonstrated that patients with PD experience rapid cognitive decline in multiple cognitive domains, specifically executive functions, attention, visuospatial, language and memory. However, the extent of cognitive decline with its correlation to brain regions on neuroimaging have not been reviewed extensively in the literature.
Objective: The objective of this review is to summarize the existing literature that explores cognitive performance in patients with PD with mild cognitive impairment (MCI) using different neuroimaging techniques.
Methods: A comprehensive search was conducted on PubMed and Web of Science databases. This review is focused on articles that explored neuroimaging and neuropsychological performance in patients with Parkinson’s disease. We screened articles and excluded those that did not fit the criteria of this study, and a total of 13 articles have met the criteria.
Results: Overall, PD-MCI patients experienced more cognitive decline than PD patients without MCI. Global cognitive ability was associated with frontal lobe, basal ganglia, para-hippocampal gyrus, occipital lobe, and the cerebellum. In addition, some specific cognitive domains were associated with specific brain regions. Attention and executive functions were associated with insula network and the parietal and frontal regions. Learning and memory were associated with grey matter atrophy and right cingulate gyrus and the limbic lobe. Language was associated with frontal cortex, precuneus, and anterior cingulate gyrus. Visuospatial ability was associated with Salience network (SN) and White Matter Hyperintensity (WMH).
Conclusion: This review of the literature showed that PD-MCI patients display different cognitive impairment as well as different neuroanatomical changes when compared to PD-Normal Cognition (NC). These findings may suggest that cognitive impairment in PD-MCI patients require different clinical treatment and care. This review also can have diagnostic and treatment implications for this group of patients.
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