Oral glutamine dipeptide or oral glutamine free amino acid reduces burned injury progression in rats

This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.

Effect of ramosetron, a 5-HT3 receptor antagonist on the severity of seizures and memory impairment in electrical amygdala kindled rats

The entorhinal cortex (EC) plays a pivotal role in epileptogenesis and seizures. EC expresses high density of serotonergic receptors, especially 5-HT3 receptors. Cognitive impairment is common among people with epilepsy. The present study investigated the role of 5-HT3 receptor on the severity of seizures and learning and memory impairment by electrical kindling of amygdala in rats. The amygdala kindling was conducted in a chronic kindling manner in male Wistar rats. In fully kindled animals, ramosetron (as a potent and selective 5-HT3 receptor antagonist) was microinjected unilaterally (ad doses of 1, 10 or 100 µg/0.5 µl) into the EC 5 min before the novel object recognition (NOR) and Y-maze tests or kindling stimulations. Applying ramosetron at the concentration of 100 μg/0.5 µl (but not at 1 and 10 µg/0.5 µl) reduced afterdischarge (AD) duration and increased stage 4 latency in the kindled rats. Moreover, the obtained data from the NOR test showed that treatment by ramosetron (10 and 100 µg/0.5 µl) increased the discrimination index in the fully kindled animals. Microinjection of ramosetron (10 and 100 µg/0.5 µl) in fully kindled animals reversed the kindling induced changes in the percentage of spontaneous alternation in Y-maze task. The findings demonstrated an anticonvulsant role for a selective 5-HT3 receptor antagonist microinjected into the EC, therefore, suggesting an excitatory role for the EC 5-HT3 receptors in the amygdala kindling model of epilepsy. This anticonvulsive effect was accompanied with a restoring effect on cognitive behavior in NOR and Y-maze tests.

Hyperlipidemia Diet Reduces Superoxide Dismutase Inhibition Rate in the Brain Organ of Rattus norvegicus

Quail (Coturnix coturnix japonica L.) egg yolk is one of the high-fat foods which can trigger hyperlipidemia. The condition of hyperlipidemia can have an oxidative stress effect on the brain. Superoxide dismutase (SOD) is a natural antioxidant that acts as a defense mechanism against oxidative stress. The inhibition rate of SOD decreases when oxidative stress occurs. This study aims to determine the effect of quail egg yolk on the SOD inhibition rate of brain organs on a rat. This study used male Wistar rats aged 2-3 months with 200-300 grams of weight. The rats were divided into two groups. Each group was fed with ad libitum for two weeks. The A groups as control continued ad libitum consumption, and the B group was given additional quail egg yolk 5 ml / 200 g BW for 2 weeks. At the end of the study, the rats were terminated. The brain organs were examined for SOD inhibition rate with spectrophotometry. The mean SOD inhibition rate in the A and B groups was 74.14% ± 6.16 and 24.14% ± 5.65, respectively. The independent t-test showed significant differences in SOD inhibition rate between groups (p 0.001). Furthermore, quail egg yolk significantly reduced the SOD inhibition rate in the brain organ of the rat.

Endogenous and exogenous serotonin, but not sumatriptan, ameliorate seizures and neuroinflammation in the pentylenetetrazole-induced seizure model in rats

ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

Effects of imidazoline agents in a rat conditioned place preference model of addiction

Agmatine (AG), idazoxan (IDZ), and efaroxan (EFR) are imidazoline receptor ligands with beneficial effects in central nervous system disorders. The present study aimed to evaluate the interaction between AG, IDZ, and EFR with an opiate, tramadol (TR), in a conditioned place preference (CPP) paradigm. In the experiment, we used five groups with 8 adult male Wistar rats each. During the condition session, on days 2, 4, 6, and 8, the rats received the drugs (saline, or TR, or IDZ and TR, or EFR and TR, or AG and TR) and were placed in their least preferred compartment. On days 1, 3, 5, and 7, the rats received saline in the preferred compartment. In the preconditioning, the preferred compartment was determined. In the postconditioning, the preference for one of the compartments was reevaluated. TR increased the time spent in the non-preferred compartment. AG decreased time spent in the TR-paired compartment. EFR, more than IDZ, reduced the time spent in the TR-paired compartment, but without statistical significance. AG reversed the TR-induced CPP, while EFR and IDZ only decreased the time spent in the TR-paired compartment, without statistical significance.

High-Salt Diet in the Pre- and Postweaning Periods Leads to Amygdala Oxidative Stress and Changes in Locomotion and Anxiety-Like Behaviors of Male Wistar Rats

High-salt (HS) diets have recently been linked to oxidative stress in the brain, a fact that may be a precursor to behavioral changes, such as those involving anxiety-like behavior. However, to the best of our knowledge, no study has evaluated the amygdala redox status after consuming a HS diet in the pre- or postweaning periods. This study aimed to evaluate the amygdala redox status and anxiety-like behaviors in adulthood, after inclusion of HS diet in two periods: preconception, gestation, and lactation (preweaning); and only after weaning (postweaning). Initially, 18 females and 9 male Wistar rats received a standard (n = 9 females and 4 males) or a HS diet (n = 9 females and 5 males) for 120 days. After mating, females continued to receive the aforementioned diets during gestation and lactation. Weaning occurred at 21-day-old Wistar rats and the male offspring were subdivided: control-control (C-C)—offspring of standard diet fed dams who received a standard diet after weaning (n = 9–11), control-HS (C-HS)—offspring of standard diet fed dams who received a HS diet after weaning (n = 9–11), HS-C—offspring of HS diet fed dams who received a standard diet after weaning (n = 9–11), and HS-HS—offspring of HS diet fed dams who received a HS diet after weaning (n = 9–11). At adulthood, the male offspring performed the elevated plus maze and open field tests. At 152-day-old Wistar rats, the offspring were euthanized and the amygdala was removed for redox state analysis. The HS-HS group showed higher locomotion and rearing frequency in the open field test. These results indicate that this group developed hyperactivity. The C-HS group had a higher ratio of entries and time spent in the open arms of the elevated plus maze test in addition to a higher head-dipping frequency. These results suggest less anxiety-like behaviors. In the analysis of the redox state, less activity of antioxidant enzymes and higher levels of the thiobarbituric acid reactive substances (TBARS) in the amygdala were shown in the amygdala of animals that received a high-salt diet regardless of the period (pre- or postweaning). In conclusion, the high-salt diet promoted hyperactivity when administered in the pre- and postweaning periods. In animals that received only in the postweaning period, the addition of salt induced a reduction in anxiety-like behaviors. Also, regardless of the period, salt provided amygdala oxidative stress, which may be linked to the observed behaviors.

Cucumeropsis mannii seed oil (CMSO) ameliorates adipokines dysfunction and dyslipidemia in male Wistar rats exposed to Bisphenol-A

Bisphenol-A (BPA) and its analog are extensively utilized in the production of plastics which are rather ubiquitous in our environment. At high temperatures, BPA is leached into water and food packed in plastic containers. This research investigated the ameliorative effects of CMSO on adipokines dysfunction and dyslipidemia in male Wistar rats exposed to Bisphenol-A. thirty-six (36) albino rats weighing 100 - 200 g were randomly assigned into six (6) different experimental groups of controls (1, 2, and 3) and the tests (4, 5, and 6). Group 1 was given only 1 ml of olive oil, group 2 received 100 mg/Kg body weight (b.w) of BPA, group 3 was given 7.5 ml/Kg b.w of CMSO, groups 4, 5, and 6 received 100 mg/Kg b.w of BPA and 7.5, 5 and 2.5 mg/Kg b.w of CMSO respectively. CMSO and BPA were concurrently administered via oral intubation for periods of 42 days. Lipid profile and adipokines levels were determined in plasma and adipose tissue. BPA in male rats significantly (p<0.05) elevated the levels of cholesterol, triglycerides, LDL-C, liptin, and coronary and atherogenic risk indices in plasma and adipose tissue with reductions in HDL-C and adiponectin levels. BPA plus CMSO in male rats significantly (p<0.05) decreased the levels of cholesterol, triglycerides, LDL-C, liptin, and coronary and atherogenic risk indices with an elevation of HDL-C and adiponectin levels in both plasma and adipose tissue. These results suggest that CMSO could be useful in the management of cardiovascular-related diseases induced by BPA.

Relationship of Anti-interleukin-6 Receptor Antibody to Interleukin-6 Level and Inducible Nitrite Oxide Levels in Peripheral Nerve Injury in Chronic Constriction Injury-Induced Rats: A Case-Control Study in Indonesia

BACKGROUND: Interleukin-6 (IL-6) and inducible Nitric oxide Synthase (iNOS) have an effect on neuropathic pain in the inflammatory process in peripheral nerve injuries. AIM: This study aims to examine the effect of anti-IL-6 receptor antibody on IL-6 and iNOS levels as a consideration for the treatment of neuropathic pain in a rat model of peripheral nerve injury. METHODS: Twenty-eight young adult male Wistar rats were treated for peripheral nerve injury and then divided into two groups. Fourteen treatment groups (Group P) were given anti-IL-6 receptor antibody by injection at a dose of 100 g/day by injection into the saphenous vein in the rat’s leg for 3 days. In both groups, the serum IL-6 and iNOS levels were assessed on the 3rd day after administration of anti-IL-6 receptor antibody in group P, using the sandwich ELISA method. RESULTS: The results showed that the administration of anti-IL-6 receptor antibody did not have a significant effect on reducing IL-6 and iNOS levels in group P (p > 0.05). Administration of anti-IL-6 receptor antibody had more effect on IL-6 levels on iNOS levels, where a decrease in IL-6 levels caused a decrease in iNOS levels in group P (p = 0.004 and r = 0.693). CONCLUSIONS: We conclude that the present administration of anti-IL-6 receptor antibody cannot be considered as a treatment for neuropathic pain in peripheral nerve injuries, but can be used to influence IL-6 levels on iNOS levels.

Ameliorative Effect of Trevo Dietary Supplement Against Lead Acetate Nephrotoxicity

Background: Trevo is a nutritional supplement with numerous bioactive natural products, with detoxifying and antioxidant properties. The purpose of this study was to investigate the ability of Trévo to protect against oxidative stress induced by lead in the kidneys of male Wistar rats. Methods: Thirty-five healthy male Wistar rats were divided into five groups of seven rats each, using a randomized design. I=control; II=15 mg/kg of lead acetate (PbA); III=2 ml/kg of trevo+PbA; IV=5 ml/kg of trevo+PbA; V=5 ml/kg of trevo. Animals were treated with trevo for five days before co-administration with lead intraperitoneally for 10 consecutive days. Animals were sacrificed 24hr after the last administration, blood samples were collected via cardiac puncture, and processed for assessment of urea, creatinine, and uric acid (UA), while the kidney samples were excised and processed for the following biochemical assays: Malondialdehyde (MDA), Glutathione-S-Transferase (GST), Catalase (CAT), Superoxide Dismutase (SOD), and Reduced Glutathione (GSH). Results: Injection of PbA caused a significant increase in the serum levels of urea, creatinine, and uric acid, and a significant increase (P<0.001) in the MDA concentration, and decreases in GSH concentration, CAT, SOD, and GST activities (P<0.05) as compared to the controls. Pretreatment with trevo prevented the oxidative stress induced by lead acetate in the kidney tissue samples and improve the renal function. The protective effect was evident at 5 ml/kg of trevo. Conclusion: The results showed that trevo was nephroprotective against lead toxicity and the activity might be linked to the presence of numerous antioxidant phytochemicals present in trevo.