Involvement of nitric oxide in myotoxicity produced by diisopropylphosphorofluoridate (DFP)-induced muscle hyperactivity.

Arch Toxicol

Toxicology Department, Breathitt Veterinary Center, Murray State University, PO Box 2000, Hopkinsville, KY 42240, USA.

Published: December 2002

Oxidative stress, as determined by increased lipid peroxidation, has been implicated in the pathology of myotoxicity. As a model system to study the response of muscle to oxidative insults, we have studied the effects of diisopropylphosphorofluoridate (DFP)-induced muscle hyperactivity on levels of nitric oxide (NO) and energy metabolites in rat skeletal muscles. In in vivo experiments, citrulline levels as indicators of NO and NO synthase (NOS), and ATP and phosphocreatine (PCr) as indicators of mitochondrial dysfunction, were determined using HPLC methods 15 min, 30 min, 60 min, 2 h, and 24 h after intoxication. Within 15 min of DFP exposure, with onset of fasciculations, citrulline levels were significantly elevated in all three muscles [soleus, extensor digitorum longus (EDL), and diaphragm]. Maximum increases in citrulline (272-288%) were noted 60 min after DFP injection. At this time point, acetylcholinesterase activity was reduced by 90-96% (soleus < diaphragm < EDL). The levels of ATP and PCr were maximally reduced (30-43%), and total adenine nucleotides, and total creatine compounds showed declines. The findings revealed that the increase in NOS activity and NO was greater than the decrease of ATP and PCr. Since memantine (MEM) has been shown to reduce nerve and muscle hyperactivity, we have studied the possible protective effect of MEM on the DFP-induced biochemical changes. Pretreatment with MEM (18 mg/kg s.c.) and atropine sulfate (16 mg/kg s.c.), 60 min and 15 min, respectively, before DFP injection prevented the increase in citrulline and muscle hyperactivity and the decrease in ATP and PCr. These data suggest that free radical reactions by depleting high-energy phosphates may be initiating the cascade of events leading to myotoxicity during DFP-induced muscle hyperactivity.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00204-002-0400-4DOI Listing

Publication Analysis

Top Keywords

muscle hyperactivity
20
dfp-induced muscle
12
min min
12
min dfp
12
atp pcr
12
nitric oxide
8
diisopropylphosphorofluoridate dfp-induced
8
citrulline levels
8
dfp injection
8
decrease atp
8

Similar Publications

Osteoma is a rare benign tumor primarily affecting the craniofacial skeleton. Coronary osteomas in the coronoid process are uncommon and asymptomatic until they affect mandibular function. This report presents a case of coronoid osteoma with its diagnosis, treatment and surgical approach.

View Article and Find Full Text PDF

Objective: To investigate the effect of hyperbaric oxygen (HBO) on paroxysmal sympathetic hyperexcitation (PSH) after brain injury.

Methods: A multicenter retrospective study was conducted. Fifty-six patients with PSH who received HBO treatment from four hospitals in Henan Province from January 2021 to September 2023 were selected as the HBO group, and 36 patients with PSH who did not receive HBO treatment from Zhengzhou People's Hospital from May 2018 to December 2020 were selected as the control group.

View Article and Find Full Text PDF

Background: Gender-affirming surgery (GAS) for transgender females developed relatively late and limited in China due to some reasons. To introduce GAS surgical experiences for Chinese transgender females is necessary.

Aims: To report surgical choices and experience including clitoral/urethral reconstruction, vaginoplasty, and vulvoplasty, and their outcomes.

View Article and Find Full Text PDF

Background: Stiff Person Spectrum Disorders (SPSD) are classically defined by the presence of muscle stiffness, spasms and hyperactivity of the central nervous system. There is a notable correlation between neurophysiological features and the clinical hallmark of SPSD, which has greatly encouraged the use of these techniques for diagnostic purposes. Besides, electrophysiological techniques allow for a functional evaluation of the 'hyperactivity of the CNS', thus offering the opportunity to clarify the mechanisms underlying this disorder.

View Article and Find Full Text PDF

One of the long-standing questions in cell signaling field to identify and characterize key signaling nodes out of a complex network. Phospholipase Cγ1 ( ) was identified as the most frequently mutated gene in adult T-cell leukemia/lymphoma, suggesting a critical function of PLCG1 in driving T cell activation. However, it remains unclear how these mutations regulate T cell physiology and pathology.

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!