Abstract:Introduction Riluzole (2-amino-6-trifluoromethoxy benzothiazole) is known as a neuroprotective, antioxidant, antiapoptotic agent. It may have beneficial effects on neuronal cell death due to cisplatin-induced ototoxicity.
Objective To evaluate the effect of riluzole on cisplatin-induced ototoxicity in guinea pigs.
Methods Twenty-four guinea pigs, studied in three groups, underwent auditory brainstem response evaluation using click and 8 kHz tone burst stimuli. Subsequently, 5 mg/kg of c… Show more
“… 30 Numerous pathways are believed to trigger the apoptosis of cochlear cells through ROS activity, such as the caspase-dependent pathway, caspase-independent pathway, lipid autoxidation, and induction of Ca 2+ influx. 31 Lipid peroxidation (autoxidation) is a chain reaction which continuously provides the supply of peroxide-free radicals and initiates the next peroxidation in the lipoprotein membrane by ROS; among which MDA belongs. 32…”
Introduction Aminoglycoside, as an antimicrobial medication, also has side-effects on the inner ears, bringing about hearing disorders. Curcumin has been proven to be a strong scavenger against various reactive oxygen species (ROS), and the increase in ROS production is considered to play an important role in the process of hearing disorder.
Objective To prove that curcumin is an effective antioxidant to prevent cochlear damage based on malondialdehyde (MDA) expression.
Methods The present research used 32 Rattus norvegicus, of the Wistar lineage, randomly divided into 8 groups: negative control, ototoxic control (a single dose of 40 mg/ml of gentamicin via intratympanic injection), 2 groups submitted to ototoxic control + curcumin treatment (100 mg/kg, 200 mg/kg), 2 groups who iunderwent ototoxic control + curcumin treatment for 7 days, and two groups submitted to curcumin treatment as prevention for 3 days + ototoxic induction.
Results The results showed that the lowest dosage of curcumin (100 mg/kg) could decrease MDA expression on the cochlear fibroblastic wall of the ototoxic model; however using greater doses of curcumin (200 mg/kg) for 7 days would provide a better effect. Curcumin could also significantly decrease MDA expression when it was administered during the preototoxic exposure.
Conclusion Curcumin can be used as a therapy for ototoxic prevention based on the decrease in MDA expression.
“… 30 Numerous pathways are believed to trigger the apoptosis of cochlear cells through ROS activity, such as the caspase-dependent pathway, caspase-independent pathway, lipid autoxidation, and induction of Ca 2+ influx. 31 Lipid peroxidation (autoxidation) is a chain reaction which continuously provides the supply of peroxide-free radicals and initiates the next peroxidation in the lipoprotein membrane by ROS; among which MDA belongs. 32…”
Introduction Aminoglycoside, as an antimicrobial medication, also has side-effects on the inner ears, bringing about hearing disorders. Curcumin has been proven to be a strong scavenger against various reactive oxygen species (ROS), and the increase in ROS production is considered to play an important role in the process of hearing disorder.
Objective To prove that curcumin is an effective antioxidant to prevent cochlear damage based on malondialdehyde (MDA) expression.
Methods The present research used 32 Rattus norvegicus, of the Wistar lineage, randomly divided into 8 groups: negative control, ototoxic control (a single dose of 40 mg/ml of gentamicin via intratympanic injection), 2 groups submitted to ototoxic control + curcumin treatment (100 mg/kg, 200 mg/kg), 2 groups who iunderwent ototoxic control + curcumin treatment for 7 days, and two groups submitted to curcumin treatment as prevention for 3 days + ototoxic induction.
Results The results showed that the lowest dosage of curcumin (100 mg/kg) could decrease MDA expression on the cochlear fibroblastic wall of the ototoxic model; however using greater doses of curcumin (200 mg/kg) for 7 days would provide a better effect. Curcumin could also significantly decrease MDA expression when it was administered during the preototoxic exposure.
Conclusion Curcumin can be used as a therapy for ototoxic prevention based on the decrease in MDA expression.
“…Recent studies have reported a prevalence of ALS between 4.1 and 8.4 per 100,000 people. In addition, a difference in ALS prevalence by ethnicity was reported in the United States [ 53 ]. Consequently, the need to find new alternatives to the current single treatment using riluzole is becoming increasingly urgent in order to treat ALS-affected patients.…”
Section: Treatments Against Chronic Neurodegenerative Disordersmentioning
The 1,3-benzothiazole (BTZ) ring may offer a valid option for scaffold-hopping from indole derivatives. Several BTZs have clinically relevant roles, mainly as CNS medicines and diagnostic agents, with riluzole being one of the most famous examples. Riluzole is currently the only approved drug to treat amyotrophic lateral sclerosis (ALS) but its efficacy is marginal. Several clinical studies have demonstrated only limited improvements in survival, without benefits to motor function in patients with ALS. Despite significant clinical trial efforts to understand the genetic, epigenetic, and molecular pathways linked to ALS pathophysiology, therapeutic translation has remained disappointingly slow, probably due to the complexity and the heterogeneity of this disease. Many other drugs to tackle ALS have been tested for 20 years without any success. Dexpramipexole is a BTZ structural analog of riluzole and was a great hope for the treatment of ALS. In this review, as an interesting case study in the development of a new medicine to treat ALS, we present the strategy of the development of dexpramipexole, which was one of the most promising drugs against ALS.
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