Reduction of the prenatal hypoxic-ischemic brain edema with noscapine

Abstract

Cytotoxic free radicals and release of several neurotransmitters such as bradykinin contribute to the pathogenesis of hypoxic-ischemic brain damage. We have studied the efficacy of noscapine, an opium alkaloid and a bradykinin antagonist, in reducing post-hypoxic-ischemic damage in developing brain of 7-d-old rat pups. Hypoxic-ischemic injury to the right cerebral hemisphere was produced by legation of the right common carotid artery followed by 3 h of hypoxia with 8% oxygen. Thirty to 45 min before hypoxia the rat pups received noscapine (dose = 0.5-2 mg/kg) or saline. Pups were scarified at 24 h post recovery for the assessment of cerebral damage by histological methods. Our results showed that noscapine was an effective agent in reducing the extent of brain injury after hypoxic-ischemic insult to neonatal rats. Therefore, it is concluded that noscapine may be a useful drug in the managements of patients after stroke.

Noscapine protects OLN-93 oligodendrocytes from ischemia-reperfusion damage: Calcium and nitric oxide involvement

“…Our results are in accord with the findings of previous studies, which pointed to the effectiveness of noscapine on hypoxic-ischemic insults (31,32). Moreover, MK-801 and NBQX, antagonists of ionotropic glutamate receptors, significantly protected the OLN-93 oligodendrocytes against oxygen-glucose deprivation/reperfusioninduced damage.…”

“…< 1 μM) presented a specific antagonistic effect on bradykinin receptors through bradykinininduced smooth muscle contraction in the isolated ileum of the guinea-pig (29). Mahmoudian et al presented the usefulness of noscapine in decreasing the extent of brain injury after hypoxic-ischemic damage in neonatal rats (32). Moreover, through a clinical trial, they show that the oral administration of noscapine to the acute ischemic stroke patients effectively improved clinical prognosis and reduced mortality without any specific side effects (31).…”

“…Furthermore, noscapine induces apoptosis dose-dependently in high concentrations (12). The important effects of noscapine on reducing the extent of ischemic brain injury in an animal model and mortality rate in stroke patients were demonstrated by Mahmoudian et al in two separate studies (31,32).…”

Combination Therapy for Cerebral Ischemia: Do Progesterone and Noscapine Provide Better Neuroprotection Than Either Alone in the Treatment ?

“…We contemplated various aspects of NOS like the ability to cross BBB; antagonism of bradykinin receptors; effect of bradykinin antagonism, ultimately reduced in ammation, on ischemia; high safety pro le; its cytoprotective activity; ease of administration and inexpensive use for the treatment of other pathological conditions (Souza et al 2003;Landen et al 2004). Moreover, PG and NOS have been reported for their bene cial effect on the ischemic injury but both agents exhibited different mechanisms to reduce brain damage (Mahmoudian et al 2003;Mahmoudian et al 2015;Moscote -Salazar et al 2018;Guennoun 2019).…”

“…Noscapine, an alkaloid attenuates oxidative stress and inhibits in ammation to reduced cerebral damage in rats and prevent cell destruction in yeast (Rida et al 2015;Kawadkar et al 2021). It readily crosses BBB (Landen et al 2004) and decreases brain edema against hypoxic/ischemic insult in neonatal rats (Mahmoudian et al 2003). Moreover, it has been reported that oral administration of noscapine (NOS) to acute ischemic stroke patients improves clinical prognosis and reduces mortality rates .…”