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.
3,4-Methylenedioxyamphetamine/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Hyperglycemia/complications/*metabolism ; Ischemic Attack, Transient/complications/*metabolism ; Lactates/metabolism ; *Lipid Peroxidation ; Male ; Rats ; Rats, Wistar

OBJECTIVETo explore the changes of methylenedioxyamphetamine (MDA), total antioxidants content (TAC) and sialic acid (SA) from the unilateral epididymis of experimental varicocele in adolescent rats, and to illuminate the effects of varicocele on unilateral epididymis epithelium.

METHODSExperimental left varicocele model of 16 adult male Sprague-Dawley rats were established by partial ligation of left renal vein. The epididymis were collected for detecting the content of MDA, TAC and SA by using spectrophotometry.

RESULTSThere was statistically significant differences in the contents of three substances between experimental varicocele and sham-operated groups.

CONCLUSIONThe content of MDA, TAC and SA will change and the sialic acid-secreting-function of unilateral epididymis will be injured because of varicocele.

Animals ; Antioxidants ; metabolism ; Epididymis ; metabolism ; Male ; N-Acetylneuraminic Acid ; metabolism ; N-Methyl-3,4-methylenedioxyamphetamine ; metabolism ; Rats ; Rats, Sprague-Dawley ; Varicocele ; metabolism

Adult ; Brain ; drug effects ; metabolism ; Female ; Hallucinogens ; adverse effects ; Humans ; Magnetic Resonance Imaging ; Motion Perception ; drug effects ; N-Methyl-3,4-methylenedioxyamphetamine ; adverse effects

OBJECTIVETo study the protective effect of peperphentonamine hydrochloride (PPTA) against gentamicin-induced cochlear damage and its mechanism to inhibit cell apoptosis.

METHODSGuinea 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.

RESULTSThe 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.

CONCLUSIONPPTA can protect against gentamicin-induced cochlear damage in guinea pigs by decreasing the protein expression of caspase-3 to inhibit cell apoptosis.

3,4-Methylenedioxyamphetamine ; analogs & derivatives ; pharmacology ; Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cochlea ; drug effects ; pathology ; Evoked Potentials, Auditory, Brain Stem ; Gentamicins ; adverse effects ; Guinea Pigs

OBJECTIVETo 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.

METHODSSixty 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.

RESULTSThe 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.

CONCLUSIONPPTA 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.

3,4-Methylenedioxyamphetamine ; analogs & derivatives ; pharmacology ; Animals ; Apoptosis Regulatory Proteins ; metabolism ; Beclin-1 ; Cochlea ; drug effects ; Endothelin-1 ; metabolism ; Gentamicins ; adverse effects ; Guinea Pigs ; Hearing Loss ; chemically induced ; prevention & control ; Microtubule-Associated Proteins ; metabolism ; Solute Carrier Family 12, Member 2 ; metabolism

3,4-Methylenedioxymethamphetamine (MDMA) is a substituted amphetamine with stimulating and hallucinogenic properties. Since MDMA induces "ecstasy" it is extensively used as a "recreational" drug. It has been well established that MDMA is neurotoxic and can result in long-term degeneration of cerebral 5-hydroxytryptamine (5-HT) nerve terminals in many species. The present study was undertaken to investigate the long-term neurotoxic effects of MDMA on cortical and hippocampal structures, by repeatedly administering MDMA in short time. Male Wistar rats were randomly assigned to control group and MDMA-treated group. MDMA (10 mg/kg) was administered to rats of MDMA-treated group, once per hour, total 40 mg/kg; rats of control group were treated with the same volume of saline. Thirty-two weeks after administering MDMA, the expression of serotonin transporter (SERT) mRNA and diazepam binding inhibitor (DBI) mRNA was detected by in situ hybridization. The expression of glial fibrillary acidic protein (GFAP) was detected by immunohistochemistry, and the degeneration of nerve terminals was demonstrated by Bielschowsky and Glee Marsland silver staining. The results showed that the expression of SERT mRNA in hippocampus decreased by 31.96%, while expression of DBI mRNA in neocortex increased by 40.51%, compared with the control group (P<0.05). The expression of GFAP in the brain tissue increased (P<0.05), while significant reduction of the nerve terminals in neocortex was demonstrated by silver staining, compared with the control group. These results suggest that the neurotoxicity of MDMA results in sustained cortical and hippocampal structural changes, which in turn result in disorder of the brain functions.
Animals ; Cerebral Cortex ; pathology ; physiopathology ; Diazepam Binding Inhibitor ; genetics ; metabolism ; Hippocampus ; pathology ; physiopathology ; Male ; N-Methyl-3,4-methylenedioxyamphetamine ; toxicity ; Neurotoxicity Syndromes ; etiology ; pathology ; physiopathology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Serotonin Plasma Membrane Transport Proteins ; genetics ; metabolism

OBJECTIVETo 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.

METHODSSixty-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.

RESULTSCompared 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).

CONCLUSIONSPPTA 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.

3,4-Methylenedioxyamphetamine ; analogs & derivatives ; pharmacology ; Animals ; Cochlea ; blood supply ; metabolism ; pathology ; Female ; Guinea Pigs ; Interleukin-1beta ; genetics ; metabolism ; Male ; Neuroprotective Agents ; pharmacology ; Organ of Corti ; metabolism ; RNA, Messenger ; metabolism ; Random Allocation ; Reperfusion Injury ; metabolism ; Spiral Ganglion ; metabolism ; Stria Vascularis ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; fas Receptor ; metabolism

OBJECTIVETo investigate whether 3,4-methylenedioxymethamphetamine (MDMA) abuse produces another neurotoxicity which may significantly inhibit the acetylcholinesterase activity and result in severe oxidative damage and liperoxidative damage to MDMA abusers.

METHODS120 MDMA abusers (MA) and 120 healthy volunteers (HV) were enrolled in an independent sample control design, in which the levels of lipoperoxide (LPO) in plasma and erythrocytes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and acetylcholinesterase (AChE) in erythrocytes were determined by spectrophotometric methods.

RESULTSCompared with the average values of biochemical parameters in the HV group, those of LPO in plasma and erythrocytes in the MA group were significantly increased (P < 0.0001), while those of SOD, CAT, GPX and AChE in erythrocytes in the MA group were significantly decreased (P < 0.0001). The Pearson product-moment correlation analysis between the values of AChE and biochemical parameters in 120 MDMA abusers showed that significant linear negative correlation was present between the activity of AChE and the levels of LPO in plasma and erythrocytes (P < 0.0005-0.0001), while significant linear positive correlation was observed between the activity of AchE and the activities of SOD, CAT and GPX (P < 0.0001). The reliability analysis for the above biochemical parameters reflecting oxidative and lipoperoxidative damages in MDMA abusers suggested that the reliability coefficient (alpha) was 0.8124, and that the standardized item alpha was 0.9453.

CONCLUSIONThe findings in the present study suggest that MDMA abuse can induce another neurotoxicity that significantly inhibits acetylcholinesterase activity and aggravates a series of free radical chain reactions and oxidative stress in the bodies of MDMA abusers, thereby resulting in severe neural, oxidative and lipoperoxidative damages in MDMA abusers.

Acetylcholinesterase ; metabolism ; Adolescent ; Adult ; Amphetamine-Related Disorders ; blood ; enzymology ; metabolism ; Catalase ; blood ; Cholinesterase Inhibitors ; adverse effects ; urine ; Erythrocytes ; enzymology ; Female ; Humans ; Lipid Peroxidation ; drug effects ; Lipid Peroxides ; blood ; Male ; N-Methyl-3,4-methylenedioxyamphetamine ; adverse effects ; urine ; Oxidative Stress ; drug effects ; Superoxide Dismutase ; blood