Altered membrane integrity has been suggested as a major factor in the development of cellular injury during myocardial necrosis. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on lysosomal hydrolases and membrane-bound phosphatases during isoproterenol (ISO) induced myocardial necrosis in rats. Induction of rats with 1SO (150 mg/kg b.wt, i.p.) for 2 days resulted in a significant increase in the activities of lysosomal hydrolases (beta-D-glucuronidase, beta-D-galactosidase, beta-D-N-acetylglucosaminidase, acid phosphatase and cathepsin-D) in the heart and serum. A significant increase in plasma lactate level, cardiac levels of sodium, calcium and a decrease in cardiac level of potassium was also observed, which was paralleled by abnormal activities of membrane-bound phosphatases (Na(+)-K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase) in the heart of ISO-administered rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt) and AA (80 mg/kg b.wt) orally for 6 days significantly attenuated these abnormalities and restored the levels to near normalcy when compared to individual drug treated groups. The combination of FA and AA preserved the membrane integrity by mitigating the oxidative stress and associated cellular damage more effectively when compared to individual treatment groups. In our study, the protection conferred by FA and AA might be through the nitric oxide pathway and by their ability of quenching free radicals. In conclusion, these findings indicate the synergistic modulation of lysosomal hydrolases and membrane phosphatases by the combination of FA and AA.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2006.09.012DOI Listing

Publication Analysis

Top Keywords

lysosomal hydrolases
16
membrane-bound phosphatases
12
mg/kg bwt
12
ferulic acid
8
acid ascorbic
8
ascorbic acid
8
membrane integrity
8
myocardial necrosis
8
compared individual
8
acid
5

Similar Publications

Children with neurodegenerative disease often have debilitating gastrointestinal symptoms. We hypothesized that this may be due at least in part to underappreciated degeneration of neurons in the enteric nervous system (ENS), the master regulator of bowel function. To test this hypothesis, we evaluated mouse models of neuronal ceroid lipofuscinosis type 1 and 2 (CLN1 and CLN2 disease, respectively), neurodegenerative lysosomal storage disorders caused by deficiencies in palmitoyl protein thioesterase-1 and tripeptidyl peptidase-1, respectively.

View Article and Find Full Text PDF

Asparagine-linked glycosylation (N-glycosylation) is a common co- and post-translational modification that refers to the addition of complex carbohydrates, called N-linked glycans (N-glycans), to asparagine residues within defined sequons of polypeptide acceptors. Some N-glycans can be modified by the addition of phosphate moieties to their monosaccharide residues, thus forming phospho-N-glycans (PNGs). The most prominent such carbohydrate modification is mannose-6-phosphate (M6P) which plays a well-established role in trafficking of acid hydrolases to lysosomes.

View Article and Find Full Text PDF

Background: Iduronate-2-sulfatase (IDS) deficiency (MPS II; Hunter syndrome) is a disorder that exhibits peripheral and CNS pathology. The blood brain barrier (BBB) prevents systemic enzyme replacement therapy (ERT) from alleviating CNS pathology. We aimed to enable brain delivery of systemic ERT by using molecular BBB-Trojans targeting endothelial transcytosis receptors.

View Article and Find Full Text PDF

Thio-ProTide strategy: A novel HS donor-drug conjugate (DDC) alleviates hepatic injury innate lysosomal targeting.

Acta Pharm Sin B

December 2024

Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, Nanjing 210009, China.

Hydrogen sulfide (HS) is a gas signaling molecule with versatile bioactivities; however, its exploitation for disease treatment appears challenging. This study describes the design and characterization of a novel type of HS donor-drug conjugate (DDC) based on the thio-ProTide scaffold, an evolution of the ProTide strategy successfully used in drug discovery. The new HS DDCs achieved hepatic co-delivery of HS and an anti-fibrotic drug candidate named hydronidone, which synergistically attenuated liver injury and resulted in more sufficient intracellular drug exposure.

View Article and Find Full Text PDF

Upregulated astrocyte HDAC7 induces Alzheimer-like tau pathologies via deacetylating transcription factor-EB and inhibiting lysosome biogenesis.

Mol Neurodegener

January 2025

College of Life Sciences and Oceanography, Brain Disease and Big Data Research Institute, Shenzhen University, Shenzhen, 518060, Guangdong, China.

Background: Astrocytes, the most abundant glial cell type in the brain, will convert into the reactive state in response to proteotoxic stress such as tau accumulation, a characteristic feature of Alzheimer's disease (AD) and other tauopathies. The formation of reactive astrocytes is partially attributed to the disruption of autophagy lysosomal signaling, and inhibiting of some histone deacetylases (HDACs) has been demonstrated to reduce the molecular and functional characteristics of reactive astrocytes. However, the precise role of autophagy lysosomal signaling in astrocytes that regulates tau pathology remains unclear.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!