Exploring the molecular mechanisms of PPARγ agonists in modulating memory impairment in neurodegenerative disorders.

Neurodegenerative diseases are characterized by progressive memory impairment and cognitive decline. This review aims to unravel the molecular mechanisms involved in the enhancement of memory function and mitigation of memory impairment through the activation of PPARγ agonists in neurodegenerative diseases. The findings suggest that PPARγ agonists modulate various molecular pathways involved in memory formation and maintenance. Activation of PPARγ enhances synaptic plasticity, promotes neuroprotection, suppresses neuroinflammation, attenuates oxidative stress, and regulates amyloid-beta metabolism. The comprehensive understanding of these molecular mechanisms would facilitate the development of novel therapeutic approaches targeting PPARγ to improve memory function and ultimately to alleviate the burden of neurodegenerative diseases. Further research, including clinical trials, is warranted to explore the efficacy, safety, and optimal use of specific PPARγ agonists as potential therapeutic agents in the treatment of memory impairments associated with neurodegenerative diseases.

Ethanol's impact on the brain: a neurobiological perspective on the mechanisms of memory impairment.

Alcohol consumption is known to have detrimental effects on memory function, with various studies implicating ethanol in the impairment of cognitive processes related to memory retention and retrieval. This review aims to elucidate the complex neurobiological mechanisms underlying ethanol-induced memory impairment. Through a thorough search of existing literature using electronic databases, relevant articles focusing on the neurobiological mechanisms of ethanol on memory were identified and critically evaluated. This review focuses on the molecular and neural pathways through which ethanol exerts its effects on memory formation, consolidation, and recall processes. Key findings from the included studies shed light on the impact of ethanol on neurotransmitter systems, synaptic plasticity, and neuroinflammation in relation to memory impairment. This review contributes to a better understanding of the intricate mechanisms by which alcohol impairs memory function, offering insights for future research directions and the development of targeted interventions to alleviate these cognitive impairments.

Beneficial effects of metformin treatment on memory impairment.

Memory issues are a prevalent symptom in different neurodegenerative diseases and can also manifest in certain psychiatric conditions. Despite limited medications approved for treating memory problems, research suggests a lack of sufficient options in the market. Studies indicate that a significant percentage of elderly individuals experience various forms of memory disorders. Metformin, commonly prescribed for type 2 diabetes, has shown neuroprotective properties through diverse mechanisms. This study explores the potential of metformin in addressing memory impairments. The current research gathered its data by conducting an extensive search across electronic databases including PubMed, Web of Science, Scopus, and Google Scholar. Previous research suggests that metformin enhances brain cell survival and memory function in both animal and clinical models by reducing oxidative stress, inflammation, and cell death while increasing beneficial neurotrophic factors. The findings of the research revealed that metformin is an effective medication for enhancing various types of memory problems in numerous studies. Given the rising incidence of memory disorders, it is plausible to utilize metformin, which is an affordable and accessible drug. It is often recommended as a treatment to boost memory.

Thymoquinone improved redox homeostasis in the heart and aorta of hypothyroid rats.

OBJECTIVES: Propylthiouracil (PTU) is a common drug that is used in medicine for treating hyperthyroidism. Furthermore, hypothyroidism can also be induced with PTU. Considering the antioxidant effects of thymoquinone (TMQ), this study was designed to find out whether TMQ could counteract the oxidative damage in the heart and aorta tissues induced by hypothyroidism in rats. METHODS: Animals were arranged into four groups: (1) Control, (2) PTU, (3) PTU-TMQ 5, and (4) PTU-TMQ 10. Hypothyroidism was induced in rats by giving 0.05% PTU in drinking water. PTU and TMQ (5 and 10 mg/kg, ip) treatments were done for 42 days. Finally, the animals were sacrificed and the serum of the rats was collected for thyroxine level assessment. The heart and aorta tissues were also removed for biochemical oxidative stress markers measurement. RESULTS: A lower serum thyroxine level was observed after PTU treatment compared to the control group. Hypothyroidism also was accompanied by a decrease of thiol content, and superoxide dismutase (SOD), and catalase (CAT) activities in the heart and aorta tissues while increased malondialdehyde (MDA). Furthermore, a significant reduction in oxidative damage was noted in the heart and aorta following the administration of TMQ (5 and 10 mg/kg) which was indicated by the reduction in MDA and improved activities of SOD, CAT, and thiol. CONCLUSION: In this study, TMQ was found to improve oxidative damages in the heart and aorta tissues of hypothyroid rats.

Cardiovascular protective effects of PPARγ agonists in hypothyroid rats: protection against oxidative stress.

Hypothyroidism disturbs redox homeostasis and takes part in cardiovascular system dysfunction. Considering antioxidant and cardio-protective effects of PPAR-γ agonists including pioglitazone (POG) and rosiglitazone (RSG), the present study was aimed to determine the effect of POG or RSG on oxidants and antioxidants indexes in the heart and aorta tissues of Propylthiouracil (PTU)-induced hypothyroid rats. MATERIALS AND METHODS: The animals were divided into six groups: (1) Control; (2) propylthiouracil (PTU), (3) PTU-POG 10, (4) PTU-POG 20, (5) PTU-RSG 2, and (6) PTU-RSG 4. Hypothyroidism was induced in rats by giving 0.05% propylthiouracil (PTU) in drinking water for 42 days. The rats of PTU-POG 10 and PTU-POG 20 groups received 10 and 20 mg/kg POG, respectively, besides PTU, and the rats of PTU-RSG 2 and PTU-RSG 4 groups received 2 and 4 mg/kg RSG, respectively, besides PTU. The animals were sacrificed, and the serum of the rats was collected to measure thyroxine level. The heart and aorta tissues were also removed for the measurement of biochemical oxidative stress markers. RESULTS: Hypothyroidism was induced by PTU administration, which was indicated by lower serum thyroxine levels. Hypothyroidism also was accompanied by a decrease of catalase (CAT), superoxide dismutase (SOD) activities, and thiol concentration in the heart and aorta tissues while increased level of malondialdehyde (MDA). Interestingly, administration of POG or RSG dramatically reduced oxidative damage in the heart and aorta, as reflected by a decrease in MDA and increased activities of SOD, CAT, and thiol content. CONCLUSION: The results of this study showed that administration of POG or RSG decreased oxidative damage in the heart and aorta tissues induced by hypothyroidism in rats.

Beneficial effects of angiotensin converting enzyme inhibition on scopolamine-induced learning and memory impairment in rats, the roles of brain-derived neurotrophic factor, nitric oxide and neuroinflammation.

The effect of the brain-derived neurotrophic factor (BDNF), cytokines, and renin angiotensin system (RAS) on memory function have been demonstrated. In this study, the effects of RAS inhibitor captopril (Capto) on hippocampal BDNF, interleukin -6 (IL-6), oxidative stress indicators, and nitric oxide (NO) in scopolamine (Sco)-induced memory impairment in rats were examined. The groups were (1) control, (2) Sco in which Sco was applied 30 min prior to the behavioral tests, and (3-5) Sco-Capto 10, 50, and 100 groups, where Capto (10, 50, or 100 mg/kg), were applied 2 weeks prior to the experiment, as well as 30 min prior to each Sco injection. The Morris Water Maze (MWM) test was conducted, and BDNF, IL-6, NO metabolites, malondialdehyde (MDA), thiol, superoxide dismutase (SOD), and catalase (CAT) were measured. Sco increased the delay and distance to the platform in the MWM test (P < .01 to P < .001), while shortening the time and distance in the target area (P < .01 to P < .001). Additionally, Sco increased IL-6, NO metabolites, and MDA, while decreasing BDNF, thiol, SOD, and CAT (P < .01 to P < .001). Although the Capto reduced the latency and distance traveled to the platform (P < .05 to P < .001), it elevated the time and distance traveled in the target area (P < .05 to P < .01). Furthermore, Capto improved BDNF, thiol, SOD, and CAT levels, and decreased IL-6, NO metabolites, and MDA (P < .05 to P < .001). RAS has a role in learning and memory impairment due to cholinergic system dysfunction. The possible mechanism(s) are including its effects on BDNF, neuro-inflammation and oxidative stress.

Losartan modulates brain inflammation and improves mood disorders and memory impairment induced by innate immune activation: The role of PPAR-γ activation.

In recent years, the role of angiotensin II (Ang II) and Ang II type 1 receptor (AT1) in the crosstalk between the immune system and the central nervous system has received more attention. The present study aimed to investigate the role of losartan, an AT1 receptor blocker, in the modulation of long-lasting adverse effects of repeated systemic lipopolysaccharide (LPS) injection in the brain function. For this purpose, 110 male BALB/c mice were administrated LPS (250 µg/kg) intraperitoneally (i.p.) for seven consecutive days. Mice were i.p. injected with losartan (1 and 3 mg/kg) three days before and during the LPS injection. To determine the role of PPAR-γ activation in the protective actions of losartan, GW9662, a PPAR-γ antagonist, was also co-administrated with losartan. Then, behavioral tests, including Morris water maze (MWM), novel object recognition test, passive avoidance, forced swim test (FST), elevated plus maze, and marble burying task, were conducted. The results demonstrated that losartan improved learning and memory impairment, attenuated anxiety-like behaviors, modulated brain inflammation and oxidative stress, and decreased amyloid-ß accumulation. Losartan was unable to improve hippocampal BDNF and IL-10 levels as well as the retention trial in the MWM task and depressive-like behaviors. In addition, the PPAR-γ antagonist did not significantly influence the beneficial effects of losartan. Our findings suggest that AT1R blockade can protect the brain against most long-lasting hallmark effects of systemic inflammation. Also, based on the results, the beneficial actions of losartan were not mediated through PPAR-γ activation.

Neuronal Nitric Oxide Inhibitor 7-Nitroindazole Improved Brain-Derived Neurotrophic Factor and Attenuated Brain Tissues Oxidative Damage and Learning and Memory Impairments of Hypothyroid Juvenile Rats.

Hypothyroidism-associated learning and memory impairment is reported to be connected to oxidative stress and reduced levels of brain-derived neurotrophic factor (BDNF). The effects of neuronal nitric oxide inhibitor 7-nitroindazole (7NI) on brain tissues oxidative damage, nitric oxide (NO), BDNF and memory impairments in hypothyroid juvenile rats were investigated. Male Wistar juvenile rats (20 days old) were divided into five groups, including Martinez et al. (J Neurochem 78 (5):1054-1063, 2001). Control in which vehicle was injected instead of 7NI, (Jackson in Thyroid 8 (10):951-956, 1998) Propylthiouracil (PTU) where 0.05% PTU was added in drinking water and vehicle was injected instead of 7NI, (Gong et al. in BMC Neurosci 11 (1):50, 2010; Alva-Sánchez et al. in Brain Res 1271:27-35, 2009; Anaeigoudari et al. in Pharmacol Rep 68 (2): 243-249, 2016) PTU-7NI 5, PTU-7NI 10 and PTU-7NI 20 in which 5, 10, or 20 mg/kg7NI was injected intraperitoneally (i.p.). Following 6 weeks, Morris water maze (MMW) and passive avoidance learning (PAL) tests were used to evaluate the memory. Finally, the hippocampus and the cortex of the rats were removed after anesthesia by urethane to be used for future analysis. The escape latency and traveled path in MWM test was increased in PTU group (P < 0.001). PTU also reduced the latency to enter the dark box of PAL and the time spent and the distance in the target quadrant in MWM test (P < 0.001 and P < 0.01). Treatment with 7NI attenuated all adverse effects of PTU (P < 0.05 to P < 0.001). PTU lowered BDNF and thiol content and superoxide dismutase (SOD) and catalase (CAT) activities in the brain but increased malondialdehyde (MDA) and nitric oxide (NO) metabolites. In addition, 7NI improved thiol, SOD, CAT, thiol, and BDNF but attenuated MDA and NO metabolites. The results of the current study showed that 7NI improvement in the learning and memory of the hypothyroid juvenile rats, which was accompanied with improving of BDNF and attenuation of NO and brain tissues oxidative damage.

Neuroprotective and long term potentiation improving effects of vitamin E in juvenile hypothyroid rats.

Protective effects of vitamin E (Vit E) on long term potentiation (LTP) impairment, neuronal apoptosis and increase of nitric oxide (NO) metabolites in the hippocampus of juvenile rats were examined. The rats were grouped (n=13) as: (1) control; (2) hypothyroid (Hypo) and (3) Hypo-Vit E. Propylthiouracil (PTU) was given in drinking water (0.05%) during 6 weeks. Vit E (20 mg/ kg) was daily injected (IP). To evaluate synaptic plasticity, LTP from the CA1 area of the hippocampus followed by high frequency stimulation to the ipsilateral Schafer collateral pathway was carried out. The cortical and hippocampal tissues were then removed to measure NO metabolites. The brains of 5 animals in each group were removed for apoptosis study. The hypothyroidism status decreased the slope, 10-90% slope and amplitude of field excitatory post synaptic potential (fEPSP) compared to the control group (P<0.01-P<0.001). Injection of Vit E increased the slope, 10-90% slope and amplitude of the fEPSP in the Hypo-Vit E group in comparison to the Hypo group (P<0.05-P<0.01). TUNEL positive neurons and NO metabolites were higher in the hippocampus of the Hypo rats, as compared to those in the hippocampus of the control ones (P<0.001). Treatment of the Hypo rats by Vit E decreased apoptotic neurons (P<0.01-P<0.001) and NO metabolites (P<0.001) in the hippocampus compared to the Hypo rats. The results of the present study showed that Vit E prevented the LTP impairment and neuronal apoptosis in the hippocampus of juvenile hypothyroid rats.

Effects of PPAR-γ agonist, pioglitazone on brain tissues oxidative damage and learning and memory impairment in juvenile hypothyroid rats.

Aim: The effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone on the brain tissues oxidative damage and learning and memory impairment in the juvenile hypothyroid rats was evaluated. Main methods: Rats were classified as: ( 1 ) Control; (2) Propylthiouracil (PTU); (3) PTU-Pio 10 and (4) PTU-Pio 20. PTU was given in drinking water (0.05%) during 6 weeks. Pioglitazone (10 or 20 mg/kg) was daily injected intraperitoneally. Passive avoidance (PA) and Morris water maze (MMW) were conducted. Later, the animals were sacrificed and the brain tissues were removed for biochemical measurements. Key funding: The results indicated that in the MWM escape latency as well as traveled path increased in the PTU group as compared to the control group. Also, the time spent in the target quadrant in the probe test of MWM and step-through latency in the PA test were decreased in the PTU group as compared to the control group. Pioglitazone reversed all the negative behavioral effects of hypothyroidism. Administration of PTU attenuated thiol and superoxide dismutase (SOD), and catalase (CAT) activities in the brain tissues, whereas increased malondialdehyde (MDA) and nitric oxide (NO) metabolites. PPARγ agonist improved thiol, SOD and CAT, while diminished MDA concentration. Significance: Our finding in the present study indicated that PPARγ agonist pioglitazone prevented the brain tissues from oxidative damage and learning and memory impairments in juvenile hypothyroid rats.

The effects of vitamin E on brain derived neurotrophic factor, tissues oxidative damage and learning and memory of juvenile hypothyroid rats.

The effects of vitamin E (Vit E) on brain derived neurotrophic factor (BDNF) and brain tissues oxidative damage as well as on learning and memory impairments in juvenile hypothyroid rats were examined. The rats were grouped as: (1) Control; (2) Propylthiouracil (PTU); (3) PTU-Vit E and (4) Vit E. PTU was added to their drinking water (0.05%) during 6 weeks. Vit E (20 mg/kg) was daily injected (IP). Morris water maze (MWM) and passive avoidance (PA) were carried out. The animals were deeply anesthetized and the brain tissues were removed for biochemical measurements. PTU increased the escape latency and traveled path in MWM (P < 0.001). It also shortened the latency to enter the dark compartment of PA as well as the time spent in the target quadrant in probe trial of MWM (P < 0.01-P < 0.001). All the effects of PTU were reversed by Vit E (P < 0.01-P < 0.001). PTU administration attenuated thiol and BDNF content as well as the activities of superoxide dismutase (SOD) and catalase (CAT) in the brain tissues while increased molondialdehyde (MDA). Moreover, Vit E improved BDNF, thiol, SOD and CAT while diminished MDA. The results of the present study showed that Vit E improved BDNF and prevented from brain tissues oxidative damage as well as learning and memory impairments in juvenile hypothyroid rats.

The effects of olibanum on male reproductive system damage in a lipopolysaccharide induced systemic inflammation model in rat.

Background: Lipopolysaccharide (LPS) as a particle of Gram-negative bacteria is a main contributer in the pathogenesis of the male reproductive system infectious. Male infertility due to LPS is reported to be related to overproduction reactive oxygen species. This study aimed to investigate the effects of olibanum on oxidative stress and apoptosis in testes and sperm dysfunction induced by LPS. Methods: The male (n = 28) rats were allocated in four groups: control, LPS (1 mg/kg, i.p., 14 days), LPS + Olibanum 100 (100 mg/kg, i.p., 14 days), and LPS + Olibanum 200 (200 mg/kg, i.p., 14 days). Germ cell apoptosis was determined by TUNEL assays and computed using the stereological method. Additionally, semen samples of the animals were analyzed for sperm count and morphology. Oxidative stress indicators were also determined. Results: The count of TUNEL-positive germ cells in LPS-treated rats was more than that in the controls. Treatment of the animals with olibanum significantly attenuated the number of apoptotic cells compared to the LPS group. The sperm count and those with a normal morphology in LPS-treated rats was lower than that in the controls. Administration of olibanum significantly improved the sperms with normal morphology and sperm count. Olibanum treatment also improved superoxide dismutase, catalase, and total thiol in testicular tissue and decreased malondialdehyde. Conclusion: Administering both doses of olibanum in LPS-treated rats had potentially a therapeutic value in reducing germ cell apoptosis, as well as improving sperm parameters.

Erythrocyte sedimentation rate and red blood cell indices association in pediatrics patients with fever and cough: A cross-sectional study.

Background and Aims: The erythrocyte sedimentation rate (ESR) is an essential inflammatory marker in treating some patients, particularly children. The level of ESR can be affected by red blood cell (RBC) indices, and not considering this can complicate the interpretation of ESR and the treatment and follow-up of patients. The study aimed to assess the association between ESR and RBC indices in children hospitalized with fever and cough in the pediatric ward of Imam Khomeini Hospital, Jiroft, in 2023. Methods: A cross-sectional study was conducted to measure the association between ESR and RBC indices in children hospitalized with fever and cough in the pediatric ward of Imam Khomeini Hospital, Jiroft, in 2023. A total of 156 patients participated in the study. SPSS software was used for statistical analysis. Results: The mean age of participants was 27.26 ± 3.14 months. The results showed that there is a significant negative correlation between ESR and RBC, r = -0.282 (p < 0.001), and ESR and hematocrit (HCT), r = -0.215 (p = 0.007). Also, the results demonstrated that there is a significant positive correlation between ESR and mean corpuscular volume (MCV), r = 0.159 (p = 0.048), ESR and mean corpuscular hemoglobin (MCH), r = 0.214 (p = 0.007), and ESR and mean cell hemoglobin concentration (MCHC), r = 0.209 (p = 0.009). There was a negative correlation between ESR and hemoglobin (Hb), r = -0.98 (p = 0.225), but this correlation was insignificant. Conclusion: This study showed an association between ESR and RBC indices in hospitalized children with complaints of fever and cough. So, it is necessary that physicians and treatment staff pay attention to the RBC indices while interpreting and following up the results of ESR to complete the treatment process of patients.

Selenium prevented renal tissue damage in lipopolysaccharide-treated rats.

OBJECTIVES: Kidney diseases are one of the common diseases, which are one of the main causes of death in society and impose costs on the health system of the society. A growing body of evidence has well documented that inflammatory responses and oxidative damage play a significant role in the progress of various kidney diseases. METHODS: This study examined whether selenium (Sel) could prevent the detrimental influences of lipopolysaccharide (LPS) in rats. Four groups of Wistar rats were considered: control, LPS (1 mg/kg, i.p., for 14 days), LPS-Sel 1 (0.1 mg/kg, i.p., for 14 days), and LPS-Sel 2 (0.2 mg/kg, i.p., for 14 days). RESULTS: Sel treatment markedly attenuated oxidative stress damage in the kidney tissue in LPS-induced renal toxicity. Generally, the administration of Sel resulted in improved antioxidant indicators such as catalase (CAT) and superoxide dismutase (SOD) activities, or total thiol content, and decreased malondialdehyde (MDA) in the kidney tissue. It also decreased interleukin-6 in kidney homogenates. Furthermore, Se treatment significantly inhibited the elevation of serum biochemical markers of kidney function including serum, BUN, and creatinine. CONCLUSIONS: Based on the findings of the current study, it seems that the administration of Sel to LPS-treated rats improves renal function by reducing oxidative damage and inflammation in kidney tissue. However, more research is needed to reveal the accurate mechanisms for the effect of Sel on renal outcomes of LPS in human subjects.

The effects of pioglitazone and rosiglitazone on liver function in hypothyroid rats.

OBJECTIVES: This study aimed to investigate the antioxidant effect of rosiglitazone (ROG) and pioglitazone (POG) on oxidative damage and dysfunction of hepatic tissue in hypothyroid rats. METHODS: The male rats were classified into six groups: (1) Control; (2) Hypothyroid, (3) Hypothyroid-POG 10, (4) Hypothyroid-POG 20, (5) Hypothyroid-ROG 2, and (6) Hypothyroid-ROG 4. To induction hypothyroidism in rats, propylthiouracil (PTU) (0.05 %w/v) was added to drinking water. In groups 2-6, besides PTU, the rats were also intraperitoneal administrated with 10 or 20 mg/kg POG or 2 or 4 mg/kg ROG for six weeks. Finally, after deep anesthesia, the blood was collected to measure the serum biochemical markers and hepatic tissue was separated for biochemical oxidative stress markers. RESULTS: Administration of PTU significantly reduced serum thyroxin concentration, total thiol levels, activity of superoxide dismutase (SOD) and catalase (CAT) enzymes, and increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (Alk-P) and malondialdehyde (MDA) in the liver. Additionally, our results showed that prescription of POG or ROG for six weeks to hypothyroid rats resulted in an improvement in liver dysfunction (decrease in serum levels of AST, ALT, and ALK-P) through reducing oxidative damage in hepatic tissue (increase in CAT, SOD, or total thiols and decrease in MDA levels). CONCLUSIONS: The findings of the present study presented that the IP administration of POG and ROG for six weeks improves liver dysfunction induced by hypothyroidism in juvenile rats by reducing oxidative damage.

The effects of PPARγ agonists on long­termpotentiation and apoptosis in the hippocampusarea of juvenile hypothyroid rats.

The aim of the present study was to evaluate the effect of rosiglitazone (RSG) or pioglitazone (POG) on the synaptic plasticity, neuronal apoptosis, brain-derived neurotrophic factor (BDNF), and nitric oxide (NO) metabolites in the hippocampus of juvenile hypothyroid rats. The animals were divided into four groups: control; propylthiouracil (PTU), 0.05% dose in drinking water for 42 days; PTU-POG; and PTU-RSG. The POG (20 mg/kg) and the RSG (4 mg/kg) were administered by IP injection. We conducted long­term potentiation (LTP) in the cornu ammonis 1 area of the hippocampus using high­frequency stimulation of the Schaffer collateral pathway. Then, the hippocampal tissues were collected to determine BDNF and NO levels and the degree of apoptosis. PTU administration decreased the slope (10-90%) and amplitude of the fEPSPs compared to control. Injection of RSG or POG increased the slope, slope (10-90%), and amplitude of the fEPSP in the PTU­POG or PTU­RSG groups compared to the PTU group. TUNEL­positive neurons and NO metabolites in the hippocampus of the PTU group were higher than those of the control group. RSG or POG increased BDNF content in PTU-POG or PTU-RSG groups. Treatment of the rats with POG or RSG decreased apoptotic neurons and NO metabolites in the hippocampus of PTU-POG or PTU-RSG groups, respectively, compared to the PTU group. This study's results revealed that POG or RSG normalized LTP impairment, neuronal apoptosis, and improved BDNF content in the hippocampal tissue of juvenile hypothyroid rats.

Rosiglitazone attenuates amyloid beta and glial fibrillary acidic protein in the hippocampus and neuroinflammation associated learning and memory impairments in rats.

OBJECTIVE: The aim of the current study was to investigate the beneficial effects of rosiglitazone (Rosi) on amyloid beta(Aß) and glial fibrillary acidic protein (GFAP) in the hippocampus and neuroinflammation-associated learning and memory impairments in rats. MATERIALS AND METHODS: The rats were grouped and treated as follows: (1) Control in which saline and vehicle were administered instead of LPS and Rosi respectively. (2) Lipopolysaccharide (LPS) group in which LPS was dissolved in saline and injected (1 mg/kg) intraperitoneally. Vehicle was administered instead of Rosi in this group. (3-5) LPS+ Rosi 1, LPS+ Rosi 3, and LPS+ Rosi 5 groups in them 1, 3, or 5 mg/kg of Rosi respectively was administered 30 min before LPS. The treatments were done for two weeks. In the first week, Rosi or its vehicle was injected 30 min before LPS. In the second week, the treatments were the same as the first week and behavioral tests were also carried out in the second week. The hippocampal tissues were finally detached for biochemical assessment. RESULTS: The results showed that Rosi reversed increased levels of Aß, GFAP, interleukin (IL)- 6, tumor necrosis factor-α (TNF-α), nitric oxide (NO) metabolites, and malondialdehyde (MDA) due to LPS injection. Rosi also reversed attenuating effects of LPS on IL-10 and thiol concentration and activities of catalase (CAT) and superoxide dismutase (SOD). In the Morris water maze test, the LPS group had a longer latency to find the platform while spent a shorter time spent in the target quadrant in the probe trial than the control group. In the passive avoidance test, the animals of the LPS group had a shorter delay to enter the dark chamber than the animals of the control group. Treatment with Rosi reversed these parameters. CONCLUSION: The findings showed Rosi attenuated Aß, GFAP, and oxidative stress in the hippocampus and neuroinflammation-associated learning and memory impairments in rats.

Vitamin E Prevented Hepatic and Renal Tissue Damage in Hypothyroid Rats.

Background: Considering antioxidant effects of vitamin E (Vit E), in the present study, the effect of Vit E on liver and kidney functions and oxidative stress parameters in tissues of these organs of hypothyroid (Hypo) rats were reported. Materials and Methods: The animals were included in three groups:(1) control, (2) hypo, and (3) hypo-hypo-Vit E. Hypothyroidism was induced in rats by giving 0.05% propylthiouracil (PTU) in drinking water. Besides PTU, the rats in group 3 were daily injected with Vit E (20 mg/kg) for 42 days. The animals were deeply anesthetized and sacrificed, and the serum of the rats was immediately removed to measure thyroxin level and subsequent analysis. The liver and kidney tissues were also immediately removed for biochemical oxidative stress criteria. Results: PTU administration reduced serum thyroxin level and also thiol content, superoxide dismutase (SOD), and catalase (CAT) activities in the liver and kidney tissues while increasing malondialdehyde (MDA). Hypothyroidism also increased alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine while decreasing albumin. Vit E increased thiol, SOD, and CAT in the liver and kidney tissues while diminished MDA. Vit E also decreased ALT, BUN, and creatinine while increased albumin. Conclusion: The results of this study showed that Vit E prevented liver and renal tissue damage in hypothyroid rats.

Exacerbated immune response of the brain to peripheral immune challenge in post-septic mice.

BACKGROUND: Mounting evidence indicates that sepsis can induce long-lasting brain dysfunction. Recently, it has been proposed that the brain may become more sensitive to systemic inflammation if microglial cells are already primed. Microglial priming has been demonstrated in aging, traumatic brain injury, and neurodegenerative diseases. There is evidence suggesting that systemic inflammation may also prime microglia. This study aimed to investigate the brain's response to a second immune challenge in sepsis survivors and the possible role of microglial priming. METHODS: Adult BALB/c mice were intraperitoneally (ip) injected with 5 mg/kg lipopolysaccharide (LPS) for sepsis induction. One month later, mice received a second immune challenge (LPS, 0.33 mg/kg). A cohort of mice was sacrificed 2 h post-LPS injection to measure inflammatory mediators mRNA expression. The second cohort of mice was tested on a battery of behavioral tests and then sacrificed, and brain tissues were removed for biochemical analyses. RESULTS: Results showed that in septic mice, secondary LPS challenge induced heightened neuroinflammation compared to the control mice, as evident by a significant increase of IL-1ß, TNF-α, and iNOS mRNA expression. In the immunochallenged septic mice, the anti-inflammatory cytokine IL-10 expression was also significantly increased compared to the control mice. Sepsis induction significantly disrupted the recognition ability in the novel object recognition, but the second immune challenge had no significant effect. However, immunochallenged septic mice exhibited more anxiety-like behavior in the marble burying task and intensive depressive-like behavior in the forced swim test. Additionally, the second immune challenge reduced arginase-1 levels in septic but not control mice. On the other hand, CIITA levels were increased more significantly in the LPS injected control mice compared to septic mice. Neither sepsis nor the second immune challenge significantly affected inhibitory avoidance behavior and Aß1-42 levels in brain tissue. CONCLUSION: Our finding suggests that low-grade immune challenge can induce exacerbated behavioral change and exaggerated inflammatory response in the brain of post-septic mice.

The effect of Cinnamomum cassia extract on oxidative stress in the liver and kidney of STZ-induced diabetic rats.

OBJECTIVES: Many diabetes-related complications are caused by oxidative stress. In the current study, the protective effect of Cinnamomum cassia against diabetes-induced liver and kidney oxidative stress was evaluated. METHODS: The male Wistar rats (n=48) were randomly divided into six groups including; control group received 500 µL normal saline orally for 42 days. Diabetes groups received intraperitoneally (i.p.) streptozotocin (STZ) as single-dose (60 mg/kg, i.p.). Cinnamon extract (100, 200, 400 mg/kg) and metformin (300 mg/kg) were orally administered to diabetic rats for 42 days. After the experiment period, the animals were anesthetized and the liver and kidney tissues were quickly removed and restored for oxidative stress evaluation. The levels of malondialdehyde (MDA), total thiol content, glutathione (GSH), nitric oxide (NO) metabolites, as well as, superoxide dismutase (SOD) and catalase (CAT) activities were measured in kidney and liver tissue. RESULTS: The level of MDA, SOD, and CAT activities increased significantly, while the total thiol content, and NO production were significantly reduced in diabetic animals compared to the control group (from p<0.05 to p<0.001). Treatment with cinnamon extract significantly decreased the MDA level, as well as, SOD and CAT activities in the liver and kidney of diabetic rats (from p<0.05 to p<0.001). In the liver and kidney of cinnamon treated groups, GSH and total thiol contents and NO production were significantly higher than diabetic group (from p<0.05 to p<0.001). CONCLUSIONS: Cinnamon extract due to its potent antioxidant property could be effective in decrease of diabetes-induced oxidative stress that plays a major role in renal and hepatic complications.