Protective effect of sesamin in lipopolysaccharide-induced mouse model of acute kidney injury via attenuation of oxidative stress,inflammation, and apoptosis

Abstract

Context: Acute kidney injury (AKI) is considered a major public health concern in today’s world. Sepsis‐induced AKI is large as a result of exposure to lipopolysaccharide (LPS) that is the major outer membrane component of Gram‐negative bacteria. Sesamin is the main lignan of sesame seeds with multiple protective effects.

Objective: In this research, we tried to demonstrate the protective effect of sesamin pretreatment in LPS-induced mouse model of AKI.

Methods: LPS was injected at a single dose of 10?mg/kg (i.p.) and sesamin was given p.o. at doses of 25, 50, or 100?mg/kg, one hour prior to LPS.

Results: Treatment of LPS-challenged mice with sesamin reduced serum level of creatinine and blood urea nitrogen (BUN) and returned back renal oxidative stress-related parameters including glutathione (GSH), malondialdehyde (MDA), and activity of catalase and superoxide dismutase (SOD). Moreover, sesamin alleviated inappropriate changes of renal nuclear factor-kappaB (NF-κB), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), tumor necrosis factor α (TNFα), interleukin-6, DNA fragmentation (an apoptotic index), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In addition, sesamin diminished magnitude of kidney tissue damage due to LPS.

Conclusion: In summary, sesamin could dose-dependently abrogate LPS-induced AKI via attenuation of renal oxidative stress, inflammation, and apoptosis.     

Protective effect of soy protein on collagen-induced arthritis in rat

To evaluate preventive and therapeutic effects of soy protein on collagen-induced arthritis rats. Sprague–Dawley rats immunized with bovine type II collagen emulsified in adjuvant and treated with soy protein (7?g/kg), dexamethasone (1?mg/kg), and casein (in control groups) by daily gavages feedings for 30?days. Score of arthritis recorded every day for each paws of animal. Tumor necrosis factor-alpha, interleukin6, leptin, and adiponectin were measured in serums. Treatment with soy protein resulted in significant delay in time to onset of arthritis as well as significantly decreased arthritis incidence, clinical arthritis severity score, histopathological arthritis severity score, and in vivo cell-mediated immunity to collagen (P?<?0.05). Administration of soy protein significantly suppressed the progression of collagen II-induced arthritis and inhibited the production of tumor necrosis factor-alpha, interleukin6, leptin, and adiponectin. Soy protein appeared to be a potent immunomodulatory inhibitor of collagen II-induced arthritis in rats. It could delay onset of RA and reduced cartilage erosion and synovitis inflammation. Therefore, it may be a useful protein in the prevention and treatment of rheumatoid arthritis patient.     

GABA(A) receptors of hippocampal CA1 regions are involved in the acquisition and expression of morphine-induced place preference.

In the present study, the effects of bilateral intra-hippocampal CA1 (intra-CA1) injections of GABA(A) receptor agonist and/or antagonist on the acquisition and expression of morphine-induced place preference in male Wistar rats have been investigated. The conditioning treatments with subcutaneous (s.c.) injections of different doses of morphine (0.5-7.5 mg/kg) induced a conditioned place preference (CPP) for the drug-associated place in a dose-dependent manner. Intra-CA1 administration of the GABA(A) receptor agonist, muscimol (0.25, 0.5 and 1 microg/rat) significantly inhibited the morphine (5 mg/kg, s.c.)-induced CPP. Intra-CA1 injections of different doses of the GABA(A) receptor antagonist, bicuculline (0.25, 0.5 and 1 microg/rat), in combination with an ineffective dose of morphine (0.5 mg/kg, s.c.) elicited a significant CPP. However, muscimol or bicuculline by themselves did not elicit any effect on place conditioning. Furthermore, the muscimol-induced inhibition of morphine response was reversed by bicuculline (1 microg/rat, intra-CA1) administration. On the other hand, the bilateral intra-CA1 injections of muscimol (0.25, 0.5 and 1 microg/rat) or bicuculline (0.5, 1 and 2 microg/rat) significantly decreased the expression of morphine-induced CPP. Intra-CA1 administration of different doses of muscimol or bicuculline had no effect on locomotor activity in the testing phase. Our data indicated that the GABA(A) receptors of the hippocampal CA1 regions may play an important role in the acquisition and expression of morphine-induced place preference.     

Effects of adrenoceptor agonists and antagonists on morphine-induced Straub tail in mice

Straub-tail behavior was induced by subcutaneous injection of different doses (10-60 mg/kg) of morphine to mice. The maximum response was obtained with 20-40 mg/kg of the drug. The response induced by morphine (40 mg/kg) was decreased by intraperitoneal administration of different doses of clonidine (0.05-0.1 mg/kg). Pretreatment of animals with yohimbine (1-4 mg/kg i.p.) reversed the inhibitory action of clonidine. Yohimbine did not elicit any response by itself. Administration of prazosin (0.25, 0.5, and 1 mg/kg) reduced the morphine response. The combination of prazosin with yohimbine (1 mg/kg), but not with clonidine (0.05 mg/kg), caused a potentiated inhibition of the morphine effect. Phenylephrine (2-6 mg/kg i.p.) did not elicit any effect by itself and also did not alter the response induced by morphine or morphine plus clonidine. Dobutamine (2.5-10 mg/kg i.p.), atenolol (2.5-10 mg/kg i.p.), salbutamol (2.5-10 mg/kg i.p.), and propranolol (2.5-10 mg/kg i.p.) did not alter morphine-induced Straub-tail behavior in mice. In conclusion, activation of alpha2-adrenergic pathways contributes to morphine-induced Straub tail, while alpha1- and beta2-adrenergic may not be involved in this phenomenon.     

Failure of gated single photon emission computer tomography scan to detect imminent acute plaque rupture causing acute ST-elevation myocardial infarction: case report

The negative predictive value of a gated single photon emission computer tomography (SPECT) scan is very high, with an event rate of < 1% in the first year. However, the presence of nonobstructive coronary artery plaque should yield normal SPECT scan findings. On the other hand, most plaque ruptures, which are a major cause of acute myocardial infarction, occur in nonobstructive coronary artery plaque. Therefore, the findings of a gated SPECT scan should be normal if a ruptured plaque has not created significant obstruction despite the imminent threat of coronary artery occlusion. We present the first case report of a documented gated SPECT scan in a patient who had experienced an acute anterior Q-wave myocardial infarction showing no significant ischemia in the anterior wall in the last minute of data acquisition.     

Cholecystokinin and GABA interaction in the dorsal hippocampus of rats in the elevated plus-maze test of anxiety

In the present study, we have investigated the effects and interaction of CCK and GABAergic systems in the dorsal hippocampus of rats using the elevated plus-maze test of anxiety. Bilateral injection of different doses of CCK(8s) (0.01, 0.05 and 0.1 microg/rat) into the dorsal hippocampus (intra-CA1) decreased percentage of open arm time (%OAT) and open arm entries (%OAE) that are representative of anxiogenic-like behavior. The bilateral injection of three doses of LY225910, a selective CCK2 receptor antagonist (0.01, 0.1 and 0.5 microg/rat) produced significant anxiolytic behavior. Although muscimol (GABA(A+)) (0.1, 0.5 and 1 microg/rat, intra-CA1) produced dose dependent increase in %OAT and a slight increase in %OAE, bicuculline (GABA(A-)), (1, 2 and 4 microg/rat, intra-CA1) failed to change the anxiety profile. Both muscimol (0.1 microg/rat) and bicuculline (1 microg/rat), when co-administered with LY225910, reversed the effect of latter drug on anxiety but when co-administered with CCK8s (0.05 microg/rat) showed no effect on anxiety profile. In conclusion, it seems that both CCK and GABAergic systems not only play a part in the modulation of anxiety in the dorsal hippocampus of rats but also have demonstrated a complex interaction as well.     

Morphine state-dependent learning: sensitization and interactions with dopamine receptors

In the present study, the effects of morphine sensitization on impairment of memory formation and the state-dependent learning by morphine have been investigated in mice. Pretraining administration of morphine (0.5, 2.5 and 5 mg/kg) dose dependently decreased the learning of a one-trial passive avoidance task. Pretest administration of morphine (0.5, 2.5 and 5 mg/kg) induced state-dependent retrieval of the memory acquired under pretraining morphine influence. Pretraining or pretest administration of naloxone (0.25, 0.5 and 1 mg/kg) reversed both responses to morphine (5 mg/kg). Amnesia induced by pretraining morphine was significantly reversed in morphine-sensitized mice which had previously received once daily injections of morphine [20 and 30 mg/kg, subcutaneously (s.c.)] for 3 days. Morphine sensitization tended to reverse but did not significantly affect morphine state-dependent memory. The inhibition of morphine-induced amnesia in morphine-sensitized mice was decreased by once daily administration of naloxone (0.5, 1 and 2 mg/kg) 30 min prior to injection of morphine (20 mg/kg/day x 3 days). Three-days administration of 1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine HCL (SKF 38393; 8, 16 and 32 mg/kg) or SCH 23390; R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCL (0.01, 0.05 and 0.1 mg/kg) before morphine (for 3 days) and during morphine-sensitization, decreased and increased, the amnesia induced by pretraining morphine, respectively. Similar administration of quinpirole (0.5, 1 and 2 mg/kg) or sulpiride (25, 50 and 100 mg/kg) before morphine also decreased and increased the amnesia induced by pretraining morphine, respectively. The results suggest that morphine sensitization affects the impairment of memory formation, but not the facilitation of retrieval induced by morphine and thus it is postulated that dopamine receptors may play an important role in this effect.     

Iridoid glycosides from Eremostachys glabra

Reversed-phase preparative HPLC of a methanol extract of the rhizomes of Eremostachys glabra yielded three new iridoid glycosides, namely, 6,9-epi-8-O-acetylshanziside methyl ester, 5,9-epi-penstemoside, and 5,9-epi-7,8-didehydropenstemoside. Their structures were elucidated on the basis of spectroscopic data interpretation. The free-radical scavenging activity of these compounds was assessed using the DPPH assay.     

Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial [ISRCTN64132371]

Background  

Attention-deficit hyperactivity disorder is an early-onset, clinically heterogenous disorder of inattention, hyperactivity, and impulsiveness. The diagnosis and treatment of attention-deficit hyperactivity disorder continues to raise controversy, and, there is also an increase in treatment options. In this 6-week double blind, placebo controlled-trial, we assessed the effects of zinc plus methylphenidate in the treatment of children with attention deficit hyperactivity disorder. To the best of our knowledge, this study is the first double blind and placebo controlled clinical trial assessing the adjunctive role of zinc in ADHD.     

Nitric oxide agents and apomorphine-induced rat behaviors

BACKGROUND: Nitric oxide (NO) may alter dopamine release in the brain. Activation of D2-dopamine receptors may suppress NO synthase, and inhibition of NO synthase prevents behaviors induced by psychostimulants. We have investigated the modulatory actions of the precursor of NO synthesis (L-arginine) and the broad-spectrum NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on apomorphine-induced behaviors in the rat. METHODS: Apomorphine was injected subcutaneously, and behaviors induced by the drug were examined in the presence or absence of intracerebroventricular administration of L-arginine and L-NAME. RESULTS: Our data indicate that L-arginine or L-NAME treatment decreased licking and yawning, but not penile erection induced by apomorphine. CONCLUSION: Apomorphine-induced behaviors may be modulated by NO levels.