Protective effect of peperphentonamine injection through the otocyst against gentamicin- induced cochlear damage in guinea pigs / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the relationship of gentamicin-induced cochlear damage with autophagy-related protein LC3, beclin1, Na(+-)K(+-)2Cl(-) cotransporter (NKCC1) mRNA and endothelin-1 (ET-1), and investigate the protective mechanism of PPTA against gentamicin-induced cochlear damage.</p><p><b>METHODS</b>Sixty guinea pigs were randomly divided into control group (with saline and artificial perilymph injections), model group (with gentamicin and artificial perilymph injections), concurrent treatment group (with gentamicin and PPTA injections), model control group (with artificial perilymph injection 7 days after gentamicin injection) and delayed treatment group (with PPTA injection 7 days after gentamicin injection). Saline and gentamicin (160 mg/kg) were injected intraperitoneally, and artificial perilymph and PPTA were injected into the otocysts on a daily basis for 7 consecutive days. Hearing impairment of the guinea pigs was analyzed with ABR, and the protein expressions of beclin1 and LC3 in cochlear tissue were tested. The expression of NKCC1 mRNA was detected with RT-PCR, and the expression of ET-1 was detected immunohistochemically.</p><p><b>RESULTS</b>The ABR thresholds in the model group and model control group were similar (P>0.05) , but significantly higher than those in the other 3 groups (P<0.05); the threshold was significantly lower in concurrent treatment group than in delayed treatment group (P<0.05). Compared with those in the other 4 groups, the expressions of LC3 II, beclin1, and NKCC1 mRNA were significantly increased in the model group (P<0.05); and those in delayed treatment group were significantly lower than those in the model control group (P<0.05). The expressions of ET-1 in the Corti organ, striavascularis and spiral ganglion were significantly higher in the model group but significantly lower in the control group than those in the other 4 groups; ET-1 expression was significantly lower in delayed treatment group than in the model control group.</p><p><b>CONCLUSION</b>PPTA offers protection against gantamicin-induced cochlear damage in guinea pigs by inhibiting cell autophagy and suppressing of NKCC1 and ET-1 expressions. Early intervention with PPTA produces better therapeutic effect, suggesting that gantamicin causes irreversible injury of the auditory cells.</p>

Peperphentonamine hydrochloride protects against gentamicin-induced cochlea damage by lowering cochlear caspase-3 expression in guinea pigs / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the protective effect of peperphentonamine hydrochloride (PPTA) against gentamicin-induced cochlear damage and its mechanism to inhibit cell apoptosis.</p><p><b>METHODS</b>Guinea pigs with normal hearing were randomized into control, gentamicin, and PPTA treatment groups, and the guinea pigs models of gentamicin-induced cochlear damage received intraperitoneal injection of PPTA. The changes of hearing of the guinea pigs were evaluated with auditory brainstem response (ABR) test, and the protein expression of caspase-3 in the cochlear tissue was detected using Western blotting. TUNEL staining, scanning and transmission electron microscopy were performed to observe the morphological changes of the cochlea.</p><p><b>RESULTS</b>The threshold in ABR in PPTA treatment group was significantly higher than that in the control group (P<0.05) but significantly lower than that in gentamicin group. Western blotting showed a significantly increased caspase-3 expression in gentamicin group (P<0.001); caspase-3 expression in PPTA group was obviously higher than that in the control group but much lower than that in gentamicin group (P<0.001). TUNEL assay and electron microscopy revealed serious damages of the hair cells in gentamicin group with numerous apoptotic cells in the organ of Corti, stria vascularis and spiral ganglion, and such cochlear damages were obviously alleviated in PPTA group.</p><p><b>CONCLUSION</b>PPTA can protect against gentamicin-induced cochlear damage in guinea pigs by decreasing the protein expression of caspase-3 to inhibit cell apoptosis.</p>

Effect of piperphentonamine hydrochloride on expressions of interleukin-1β and TNF-α mRNA and Fas protein in guinea pigs with cochlear ischemia/reperfusion injury / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between IL-1β and TNF-α mRNA and Fas protein expressions and cochlear ischemia reperfusion injury and investigate the protective mechanism of PPTA against cochlear reperfusion injury.</p><p><b>METHODS</b>Sixty-four guinea pigs were randomly divided into normal control group, blank control group, ischemia/reperfusion (by clamping the bilateral vertebral artery and right common carotid artery for 1 h) control group, and ischemia/reperfusion with PPTA treatment group. In PPTA group, PPTA was injected via the femoral vein immediately after reperfusion, and ischemia/reperfusion control group received saline injection. In 6 guinea pigs from each group, the cochlear tissues were removed after 24 h of reperfusion for examination of expressions of IL-1β and TNF-α mRNA by real-time PCR, and the rest animals were used for immunohistochemical detection of Fas protein.</p><p><b>RESULTS</b>Compared with those of normal group and blank control group, the expressions of IL-1β and TNF-β mRNA increased significantly after cochlear ischemia/reperfusion (P<0.001), but were lowered significantly by PPTA (P<0.001). Positive expression of Fas protein expression was detected in the Corti organ, spiral ganglion and stria vascularis in ischemia/reperfusion control group with significantly higher IOD values than those of the other 3 groups (P<0.05). The IOD value showed no significant difference between PPTA-treated group, normal control group, and blank control group (P>0.05).</p><p><b>CONCLUSIONS</b>PPTA can suppress the expression of Fas protein and IL-1β and TNF-β mRNAs in the cochlea of guinea pigs with cochlear ischemia/reperfusion. The protective effect of PPTA against cochlear ischemia/reperfusion is mediated probably by inhibition of inflammatory responses and cell apoptosis.</p>

Effects of piperphentonamine hydrochloride on cognitive deficits in rats induced by cerebral ischemia-reperfusion / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of piperphentonamine hydrochloride (PPTA) on cognitive deficits induced by ischemia-reperfusion and explore the possible mechanisms.</p><p><b>METHODS</b>SD rats were randomly divided into sham-operated group, ischemia-reperfusion group (with saline injection), PPTA-treated groups (2.5, 5, 10 mg/kg) and edaravone-treated group (6 mg/kg). Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion, and the agents were administrated 1 h after ischemia. At 24 h after ischemia, step-through passive avoidance test was carried out, and 24 h later IL-1β, TNF-α, caspase-3 and HSP-70 mRNA expressions in the ischemic brain tissues were measured with RT-PCR.</p><p><b>RESULTS</b>In the step-through passive avoidance test, the rats in the ischemia-reperfusion group showed significantly shorter latency and more error times than those in the sham group, and these behavioral changes were improved significantly by treatments with PPTA and edaravone. Cerebral ischemia-reperfusion caused significantly increased expressions of IL-1β, TNF-α, caspase-3 and HSP-70 mRNA, and these changes were obviously reversed by PPTA, but not by edaravone.</p><p><b>CONCLUSIONS</b>PPTA can reverse cognitive deficits induced by cerebral ischemia-reperfusion probably by decreasing the inflammatory responses and cell apoptosis in the brain, suggesting its potential as a new therapeutic agent for improving the cognitive function following cerebral ischemia-reperfusion.</p>

Modulaçäo do estresse oxidativo em glândulas submandibulares de rato / Modulation of oxidative stress in rat submandibular glands

As espécies reativas de oxigênio geradas in vivo têm sido implicadas em vários mecanismos como apoptose, crescimento e diferenciação celular, câncer e inflamação. O estresse oxidativo é o produto do desbalanço entre os agentes pro-oxidantes e antioxidantes celulares, causando danos por meio da peroxidação lipídica, oxidação de proteínas e de DNA. Neste trabalho, avaliou-se o efeito do estresse oxidativo em glândulas submandibulares de rato e em células acinares dispersas tratadas com isoproterenol (ISO), cicloheximida (CHX), carbacol (CA) e propanolol (PROP). Observou-se aumento dos níveis de MDA em homogenados de glândulas de ratos tratados com ISO e CHX e em células acinares dispersas incubadas com ISO e CHX...

Drogas desenhadas: novas drogas de abuso? / Designer drugs: new drugs of abuse

Os autores fazem uma revisäo das "drogas desenhadas" - específicamente o MDMA, a metcatinona e o alfa-metil-fentanil, substâncias sintéticas produzidas ilegalmente em laboratório; enfatizam suas propriedades, seu uso crescente na populaçäo e a importância do diagnóstico de manifestaçöes pelo uso dessas drogas

Identificaçäo de 3, 4-metilenodioximetanfetamina (MDMA) e compostos relacionados por cromatografia em fase gasosa e espectrometria de massas em comprimidos de Ecstasy apreendidos em Säo Paulo / Identification of 3, 4-methylenedioxymethamphetamine (MDMA) and related compounds by gas chromatography-mass spectrometry in Ecstasy tablets seized in Säo Paulo, Brazil

Foram analisados comprimidos de Ecstasy provenientes de sete diferentes lotes da droga apreendidos em Säo Paulo, visando à pesquisa de metilenodioxifenilalquilaminas. Em seis amostras foi detectada a presença de 3, 4-metilenodioximetanfetamina (MDMA), sendo que numa delas foi encontrada também cafeína. Apenas numa, foi identificada a 3, 4-metilenodioxietilanfetamina (MDEA). A cromatografia em fase gasosa com detector de nitrogênio/fósforo (CG/DNP) e a espectrometria de massas acoplada à cromatografia em fase gasosa (CG/EM) foram utilizadas como técnica de triagem e confirmaçäo, respectivamente

The effect of hyperglycemia on lipid peroxidation in the global cerebral ischemia of the rat

To investigate the influence of hyperglycemia on ischemic brain damage, we measured brain ATP, lactate and malondialdehyde (MDA) levels in global cerebral ischemic models of Wistar rats. We induced global cerebral ischemia by the 4-vessel occlusion method. After 30 or 60 min of occlusion, and after 30 min of reperfusion, we measured brain ATP, lactate and MDA levels. During the ischemic period, brain ATP levels decreased to 30-70% of sham groups both in normoglycemic and hyperglycemic groups. But during the reperfusion period, the recovery rate of ATP levels was significantly lower in the hyperglycemic than in the normoglycemic groups (p less than 0.05). After 60 min of global ischemia, brain lactate increased much more in the hyperglycemic than in the normoglycemic group, and, during reperfusion, was washed out slowly in the hyperglycemic group. The MDA level, a parameter of lipid peroxidation, increased more in the hyperglycemic group than in the normoglycemic group during reperfusion periods (p less than 0.05). We conclude that hyperglycemia increases lactate accumulation, delays the recovery of energy metabolism, and enhances the lipid peroxidation in the transient global ischemia of rat brain. These findings may suggest the harmfulness of hyperglycemia in clinical cerebral ischemia.