Riluzole prevents morphine-induced apoptosis in rat cerebral cortex

Abstract

Neuronal apoptosis has been shown to be associated with the development of tolerance to morphine. In the present study, we investigated the effect of intracerebroventricular (icv) administration of an inhibitor of glutamate release, riluzole, on morphine-induced apoptosis in the rat cerebral cortex. Various groups of rats received either morphine (intraperitoneally, ip) and vehicle (icv) or morphine (ip) and different doses of riluzole (icv) once per day for 8 days. An in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method was used as an apoptosis assay. Levels of the anti-apoptotic factors Bcl-2 and HSP70 and the pro-apoptotic agent caspase-3 were evaluated by immunoblotting. The glutamate concentration in the cerebral cortex was measured by high performance liquid chromatography (HPLC). The results showed that icv administration of riluzole decreased the number of apoptotic cells in the cerebral cortex compared with the control group, which was treated with morphine (ip) and 1% Tween 80 in 0.9% normal saline (icv). The levels of the anti-apoptotic proteins Bcl-2 and HSP70 were higher in the riluzole groups than in the control. Furthermore, co-administration of riluzole with morphine significantly decreased caspase-3 protein levels and glutamate content of the cerebral cortex compared with the control. In conclusion, we found that icv administration of riluzole attenuates morphine-induced apoptosis in the cerebral cortex after the development of morphine tolerance.

n‐butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1G93A mouse model of amyotrophic lateral sclerosis

“…Based on these previous research reports, BP may decrease the expression of BH3‐only proteins to counter against the apoptosis of motor neurons . Consistent with the previous studies, we found that riluzole augmented the level of Bcl‐2 and suppressed the levels of cleaved caspase‐3, Bax, and cleaved PARP, and exhibit antiapoptosis activity . Interestingly, we documented that the expression levels of cleaved PARP and Bax in BP‐treated SOD1 G93A mice were significantly lower than that in riluzole‐treated SOD1 G93A mice (Figure F,H), indicating that regulating apoptosis may become an important action for BP to protect the motor neurons in this mouse model of ALS.…”

Geranylgeranylacetone protects against morphine-induced hepatic and renal damage in mice

“…Besides the cytoprotection in the liver and kidney, GGA also exerts protective effects against various stresses in other organs, including the heart and brain (37)(38)(39). The toxicities of morphine in a number of tissues, including the spinal cord and brain, have also been reported (40,41). Whether or not GGA is able to protect against morphine-induced toxicity in other organs remains to be elucidated.…”

“…The mouse model of morphine dependence was created as described in our previous study (29). The mice were injected with escalating morphine doses twice daily (10,20,40,60,80 and 100 mg/kg) for 7 days. Two hours following the last morphine injection, the mice were sacrificed using deep anesthesia, and then heart perfusion was performed using saline.…”

Impact of Prunus Cerasus on PGR and HAS2 in Cumulus Cells and Fertility Outcome

“…12 Recent studies have shown that reproductive processes may be influenced by hypothalamic-pituitarygonadal axis via scavenging free radicals. [13][14][15] However, interest in antioxidant has recently been intensified because of their possible effect on egg quality, fertilization, and pregnancy rates. 16,17 Antioxidant therapy has been attended to alleviate infertility, and dietary antioxidant has been beneficial for female reproductive disorder.…”