Resveratrol, a novel inhibitor of GLUT9, ameliorates liver and kidney injuries in a d-galactose-induced ageing mouse model via the regulation of uric acid metabolism

Accumulating evidence has shown that chronic injection of d-galactose (d-gal) can mimic the natural aging, accompanying with liver and kindey injury. Previous studies have shown that d-gal-induced uric acid (UA)...

Reduced Levels of Intestinal Neuropeptides and Neurotrophins in Neurotoxin-Induced Parkinson Disease Mouse Models

Intestinal neuropeptides and neurotrophins as endocrine messengers play a key role in the bidirectional gut-brain interaction both in health and disease status. Their alterations in several neurological disorders have been reported, but whether a remarkable change occurs in Parkinson disease (PD) remains unexplored. In this study, we aimed to investigate the levels of 13 neuropeptides and 4 neurotrophins in the intestine of neurotoxin-induced PD mice. The PD mice were obtained by chronic injection of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) or MPTP/probenecid (MPTP/p). The levels of mRNA and protein expression in mouse intestines were measured by using real-time reverse transcription polymerase chain reaction and Western blotting, respectively. We found that the mRNA expression of 2 neuropeptides (cholecystokinin [CCK] and dynorphin A [Dyn A]) and 2 neurotrophins (brain-derived neurotrophic factor [BDNF] and neurotrophin-5) was significantly decreased in the colon of MPTP group compared to the vehicle-treated group. The protein levels of CCK, Dyn A, and BDNF were reduced in the colon of MPTP- or MPTP/p-treated mice compared to those of the vehicle-treated group. These data suggest that the intestinal expression of CCK, Dyn A, and BDNF was significantly reduced in PD animal models, and may play a role in the gut-brain axis in PD.

Reproductive toxicity of manganese dioxide in forms of micro- and nanoparticles in male rats

Background: Manganese Dioxide (MnO2) has long been used in industry, and its application has recently been increasing in the form of nanoparticle. Objective: The present study was an attempt to assess the effects of MnO2 nanoparticles on spermatogenesis in male rats. Materials and Methods: Micro- and nanoparticles of MnO2 were injected (100 mg/kg) subcutaneously to male Wistar rats (150 ± 20 gr) once a week for a period of 4 weeks, and the vehicle group received only normal saline (each group included 8 rats). The effect of these particles on the bodyweight, number of sperms, spermatogonia, spermatocytes, diameter of seminiferous tubes, testosterone, estrogen, follicle stimulating factor, and the motility of sperms were evaluated and then compared among the control and vehicle groups as the criteria for spermatogenesis. Results: The results showed that a chronic injection of MnO2 nanoparticles caused a significant decrease in the number of sperms, spermatogonia, spermatocytes, diameter of seminiferous tubes (p < 0.001) and in the motility of sperms. However, no significant difference was observed in the weight of prostate, epididymis, left testicle, estradiol (p = 0.8) and testosterone hormone (p = 0.2). Conclusion: It seems that the high oxidative power of both particles was the main reason for the disturbances in the function of the testis. It is also concluded that these particles may have a potential reproductive toxicity in adult male rats. Further studies are thus needed to determine its mechanism of action upon spermatogenesis.

Abstract P103: Anti-hypertensive Mechanisms of Action of G q/11 Inhibitor Ligands

Chronic blockade of individual G protein coupled receptors (GPCRs) has proven to be inadequate strategy for managing hypertension partly because the subcellular heterotrimeric G proteins that propagate intracellular signaling can simultaneously couple to several other vasopressor receptors. Whether blood pressure can better be controlled by directly targeting G proteins has not been thoroughly investigated due to paucity of selective, cell-permeable inhibitors. Here, we tested whether chemical inhibition of Gq/11 proteins in vivo and ex vivo using recently discovered small-molecule inhibitor ligands, YM-254890 (YM), FR-900359 (FR) and WU-07047 (WU) is sufficient to reverse hypertension in mice. Using ex vivo vessel reactivity assay, we found that Gq/11 inhibitors markedly reduced vasoconstriction evoked with phenylephrine (PE), vasopressin, endothelin-1, and the thromboxane analog U-46619. Blockade of PE-induced contractility by the Gq/11 inhibitors showed the following rank-order potency: FR LogIC50 -0.008 ± 0 > YM LogIC50 -0.49 ± 0 > WU LogIC50 -64.95 ± 6.4. YM and WU but not FR inhibited PE-induced vasoconstriction through G protein-dependent and independent pathways by blocking L-type calcium channel-mediated Ca 2+ influx. Acute subcutaneous injection of FR and YM (0.3 mg/kg, s.c.) in normotensive and N ω -Nitro-L-arginine methyl ester (L-NAME) hypertension mice elicited marked hypotension, which was more severe (ΔSBP = -25 ± 2.7 vs. ΔSBP = -21 ± 2.2 mmHg) and long lasting (FR t1/2 ≅ 12 hr vs. YM t1/2 ≅ 4 hr) after the injection of FR relative to YM. In DOCA-salt hypertension mice, chronic injection of FR (0.3 mg/kg, s.c., daily for seven days) reversed hypertension (vehicle SBP: 149 ± 5 vs. FR SBP: 117 ± 7 mmHg) and sustained blood pressure reduction several days after terminating the injection regimen (DOCA SBP: 141 ± 2 vs. SBP 5 days post FR: 128 ± 5 mmHg). Our results together support the hypothesis that increased Gq/11 activity in blood pressure-regulating organs is involved in the pathogenesis of hypertension, and that direct systemic blockade of Gq/11 reverses hypertension. The findings provide clear evidence for targeting Gq/11 in the cardiovascular system as an effective therapy for treating hypertension.

Polydatin attenuatesd-galactose-induced liver and brain damage through its anti-oxidative, anti-inflammatory and anti-apoptotic effects in mice

Accumulating evidence has shown that chronic injection ofd-galactose (d-gal) can mimic natural aging, with accompanying liver and brain injury.

Alleviation of Morphine Withdrawal Signs but Not Tolerance by the Essential Oil ofKelussia odoratissimaMozaff.

The aim of the present study was to assess the effects of chronic and acute treatment of the essential oil (EO) ofKelussia odoratissimaMozaff. on the development of morphine tolerance and dependence in mice. Mice were rendered tolerant to and dependent on morphine by subcutaneous injection of morphine over a period of 5 days. Tolerance was assessed using the tail-pinch test and withdrawal signs of morphine were precipitated by injecting naloxone 2 h after the final morphine injection. Repeated injection of the EO ofK. odoratissima(5 and 10 mg/kg) for 4 days significantly suppressed morphine-withdrawal jumps, a sign of the development of dependence to opiate as assessed by naloxone precipitation withdrawal on day 5 of testing. A single injection (25, 50, 100 mg/kg) of the EO on day 5, 1 h prior to morphine failed to produce any significant change in morphine withdrawal signs. Neither the acute nor the chronic administration of EO of theK. odoratissimadid significantly influence the development of tolerance to the analgesic effect of morphine. Alleviation in morphine signs of withdrawal after chronic injection withK. odoratissimais indicative of reversal of neuronal adaptation that takes place during morphine presence in the brain.

Effects of chronic progesterone injection on performance, plasma hormones and ovarian morphology of feed-satiated and fed restricted broiler breeder hens

Single injection of chronic dose of P4 in laying hens during the preovulatory open period has been shown to have positive effects on inducing a preovulatory LH surge and ovulation (Johnson et al., 1985). However, chronic injection of P4 has been shown to increase baseline concentrations of P4 and result in arrested laying and disrupted distribution of hierarchical follicles in turkeys (Bacon and Liu, 2004). The current study was designed to examine the effects of a simulated progesterone surge (by injection of chronic dose of P4) on broiler breeder hens performance, ovary morphology, plasma metabolites and hormones concentrations in either feed-satiated or feed-restricted hens.