Protective effects of 17-ß-estradiol on liver injury: The role of TLR4 signaling pathway and inflammatory response.

Liver injury, a major global health issue, stems from various causes such as alcohol consumption, nonalcoholic steatohepatitis, obesity, diabetes, metabolic syndrome, hepatitis, and certain medications. The liver's unique susceptibility to ischemia and hypoxia, coupled with the critical role of the gut-liver axis in inflammation, underscores the need for effective therapeutic interventions. The study highlights E2's interaction with estrogen receptors (ERs) and its modulation of the Toll-like receptor 4 (TLR4) signaling pathway as key mechanisms in mitigating liver injury. Activation of TLR4 leads to the release of pro-inflammatory cytokines and chemokines, exacerbating liver inflammation and injury. E2 down-regulates TLR4 expression, reduces oxidative stress, and inhibits pro-inflammatory cytokines, thereby protecting the liver. Both classic (ERα and ERß) and non-classic [G protein-coupled estrogen receptor (GPER)] receptors are influenced by E2. ERα is particularly crucial for liver regeneration, preventing liver failure by promoting hepatocyte proliferation. Furthermore, E2 exerts anti-inflammatory, antioxidant, and anti-apoptotic effects by inhibiting cytokines such as IL-6, IL-1ß, TNF-α, and IL-17, and by reducing lipid peroxidation and free radical damage. The article calls for further clinical research to validate these findings and to develop estrogen-based treatments for liver injuries. Overall, the research emphasizes the significant potential of E2 as a therapeutic agent for liver injuries. It advocates for extensive clinical studies to validate E2 hepatoprotective properties and develop effective estrogen-based treatments.

Caloric and time restriction diets improve acute kidney injury in experimental menopausal rats: role of silent information regulator 2 homolog 1 and transforming growth factor beta 1.

BACKGROUND: Estrogen has a protective impact on acute kidney injury (AKI); moreover, reducing the daily intake of calories impedes developing diseases. The present study aimed to determine the effects of calorie restriction (CR) and time restriction (TR) diets on the expression of silent information regulator 2 homolog 1 (SIRT1), transforming growth factor beta 1 (TGF-ß1), and other indicators in the presence and absence of ovaries in AKI female rats. METHODS: The female rats were divided into two groups, ovariectomized (OVX) and sham, and were placed on CR and TR diets for eight weeks; afterward, AKI was induced by injecting glycerol, and kidney injury indicators and biochemical parameters were measured before and after AKI. RESULTS: After AKI, the levels of urine albumin excretion rate, urea, and creatinine in serum, and TGF-ß1 increased, while creatinine clearance and SIRT1 decreased in kidney tissue. CR improved kidney indicators and caused a reduction in TGF-ß1 and an increase in SIRT1 in ovary-intact rats. Moreover, CR prevented total antioxidant capacity (TAC) decrease and malondialdehyde (MDA) increase resulting from AKI. Before AKI, an increase in body weight, fasting blood sugar (FBS), low-density lipoprotein (LDL), triglyceride (TG), and total cholesterol (TC), and a decrease in high-density lipoprotein (HDL) were observed in OVX rats compared to sham rats, but CR prevented these changes. The effects of TR were similar to those of CR in all indicators except for TGF-ß1, SIRT1, urea, creatinine, and albumin. CONCLUSION: The present study indicated that CR is more effective than TR in preventing AKI, probably by increasing SIRT1 and decreasing TGF-ß1 in ovary-intact animals.

Beneficial effects of time and energy restriction diets on the development of experimental acute kidney injury in Rat: Bax/Bcl-2 and histopathological evaluation.

People's lifestyles and, especially, their eating habits affect their health and the functioning of the organs in their bodies, including the kidneys. One's diet influences the cells' responses to stressful conditions such as acute kidney injury (AKI). This study aims to determine the preconditioning effects of four different diets: energy restriction (ER) diet, time restriction (TR) eating, intermittent fasting (IF), and high-fat diet (HF) on histopathological indices of the kidney as well as the molecules involved in apoptosis during AKI. Adult male rats underwent ER, TR, IF, and HF diets for eight weeks. Then, AKI was induced, and renal function indices, histopathological indices, and molecules involved in apoptosis were measured. In animals with AKI, urinary albumin excretion, serum urea, creatinine and, Bax/Bcl-2 ratio increased in the kidney, while renal eGFR decreased. ER and TR diets improved renal parameters and prevented an increase in the Bax/Bcl-2 ratio. The IF diet improved renal parameters but had no effect on the Bax/Bcl-2 ratio. On the other hand, the HF diet worsened renal function and increased the Bax/Bcl-2 ratio. Histopathological examination also showed improved kidney conditions in the ER and TR groups and more damage in the HF group. This study demonstrated that ER and TR diets have renoprotective effects on AKI and possibly cause the resistance of kidney cells to damage by reducing the Bax/Bcl-2 ratio and improving apoptotic conditions.

The Role of Inhaled Estradiol and Myrtenol, Alone and in Combination, in Modulating Behavioral and Functional Outcomes Following Traumatic Experimental Brain Injury: Hemodynamic, Molecular, Histological and Behavioral Study.

BACKGROUND: Traumatic brain injury (TBI) is an important and growing cause of disability worldwide, and its cognitive consequences may be particularly significant. This study assessed the neuroprotective impacts of estradiol (E2), myrtenol (Myr), and the combination of the two on the neurological outcome, hemodynamic parameters, learning and memory, brain-derived neurotrophic factor (BDNF) level, phosphoinositide 3-kinases (PI3K/AKT) signaling, and inflammatory and oxidative factors in the hippocampus after TBI. METHODS: Eighty-four adult male Wistar rats were randomly divided into 12 groups with seven rats in each (six groups to measure intracranial pressure, cerebral perfusion pressure, brain water content, and veterinary coma scale, and six groups for behavioral and molecular studies): sham, TBI, TBI/vehicle, TBI/Myr, TBI/E2, and TBI/Myr + E2 (Myr 50 mg/kg and E2 33.3 µg/kg via inhalation for 30 min after TBI induction). Brain injury was induced by using Marmarou's method. Briefly, a 300-g weight was dropped down from a 2-m height through a free-falling tube onto the head of the anesthetized animals. RESULTS: Veterinary coma scale, learning and memory, brain water content, intracranial pressure, and cerebral perfusion pressure were impaired following TBI, and inflammation and oxidative stress were raised in the hippocampus after TBI. The BDNF level and PI3K/AKT signaling were impaired due to TBI. Inhalation of Myr and E2 had protective effects against all negative consequences of TBI by decreasing brain edema and the hippocampal content of inflammatory and oxidant factors and also by improving BDNF and PI3K/AKT in the hippocampus. Based on these data, there were no differences between alone and combination administrations. CONCLUSIONS: Our results propose that Myr and E2 have neuroprotective effects on cognition impairments due to TBI.

The protective effects of 17-ß estradiol and SIRT1 against cardiac hypertrophy: a review.

One of the major causes of morbidity and mortality worldwide is cardiac hypertrophy (CH), which leads to heart failure. Sex differences in CH can be caused by sex hormones or their receptors. The incidence of CH increases in postmenopausal women due to the decrease in female sex hormone 17-ß estradiol (E2) during menopause. E2 and its receptors inhibit CH in humans and animal models. Silent information regulator 1 (SIRT1) is a NAD+-dependent HDAC (histone deacetylase) and plays a major role in biological processes, such as inflammation, apoptosis, and oxidative stress responses. Probably SIRT1 because of these effects, is one of the main suppressors of CH and has a cardioprotective effect. On the other hand, estrogen and its agonists are highly efficient in modulating SIRT1 expression. In the present study, we review the protective effects of E2 and SIRT1 against CH.

The effects of exercise on kidney injury: the role of SIRT1.

In patients with kidney injury, muscle mass and strength decrease with altered muscle protein synthesis and degradation along with complications such as inflammation and low physical activity. A treatment strategy to maintain muscle metabolism in kidney injury is important. One of the proposed strategies in this regard is exercise, which in addition to inducing muscle hypertrophy, reducing plasma creatinine and urea and decreasing the severity of tubal injuries, can boost immune function and has anti-inflammatory effects. One of the molecules that have been considered as a target in the treatment of many diseases is silent information regulator 1 (SIRT1). Exercise increases the expression of SIRT1 and improves its activity. Therefore, studies that examined the effect of exercise on kidney injury considering the role of SIRT1 in this effect were reviewed to determine the direction of kidney injury research in future regarding to its prevalence, especially following diabetes, and lack of definitive treatment. In this review, we found that SIRT1 can be one of renoprotective target pathways of exercise. However, further studies are needed to determine the role of SIRT1 in different kidney injuries following exercise according to the type and severity of exercise, and the type of kidney injury.

Nicotine-conditioned place preference, reversal learning and social interaction in MK-801-induced schizophrenia model: Effects of post-weaning enriched environment.

Based on the clinical observations of severe cognitive deficits in schizophrenia patients and the relationship between environmental parameters and the severity of schizophrenia symptoms, the present study investigated these parameters in an dizocilpine (MK-801)-induced schizophrenia model in rats. In addition to, it evaluated whether a post-weaning enriched environment (EE) would affect the nicotine-induced conditioned place preference (CPP) and the motor and cognitive deficits caused by MK-801 treatment. Male Wistar rat pups were injected peritoneally with MK-801 (1 mg/kg) on a daily basis between the 6th and the 10th postnatal days (P) and were exposed to either an enriched or a standard cage from P21 until the end of the experiments. The rats were evaluated in open-field and three-chamber social interaction tests. Moreover, spatial and reversal learning was assessed by the Morris water maze (MWM). The animals were conditioned with 0.6 mg/kg nicotine and tested for CPP. Increased self-grooming, exploratory behaviour, potentiated nicotine-CPP and decreased social behaviours, delayed spatial learning and memory and impaired reversal learning in the water maze were observed in the MK-801 treatment group. Housing in an EE improved cognitive and behavioural deficits associated with postnatal MK-801 treatment. The results suggested that neonatal N-methyl-d-aspartate (NMDA) receptor hypofunction may cause susceptibility to these behaviours and indicated the importance of environmental conditions in the development of schizophrenia and probably other neuropsychiatric disorders.

The effect of two types of diet on apoptosis indexes, lipid profile and histopathological outcome in acute kidney injury during exercise.

BACKGROUND: Exercise and some pre-AKI diets have been shown to improve injury, apoptosis, and lipid profile. In this study, the effect of two different diets along with exercise training on acute kidney injury (AKI) was investigated.  MATERIALS AND METHODS: Laboratory rats were randomly divided into four groups of control, standard diet + exercise, exercise + calorie restriction (CR) and exercise + time restriction (TR). Each group was divided into two subgroups of AKI and no AKI. The animals received endurance training and diet regimens before AKI. Fasting blood glucose, serum creatinine, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl2) and histopathological outcome of renal tissue as well as serum lipid profile of animals were assessed 24 h after AKI.  RESULTS: The percentage of changes in renal Bcl2 and Bax after AKI in the group with previous exercise was lower than the group without previous exercise (p < 0.01). After induction of AKI, serum lipid profile changed in non-exercised rats (p < 0.001). Also, after injury, fasting blood glucose levels increased in non-exercised rats (p < 0.05). After injury, the start of both CR and TR diets during exercise caused less change in Bcl2 and Bax of non-exercised rats compared to exercised rats (p < 0.001). CR diet along with exercise improved lipid profile, and also CR diet along exercise decreased fasting blood glucose levels (p < 0.001). Also, both the CR and TR diets during exercise caused fewer changes in histopathological outcome after AKI. CONCLUSION: Exercise alone decreased changes in apoptotic and histopathological indexes, fasting blood glucose, as well as lipid profile of rats after AKI. Reduction of apoptosis and improvement of histopathological outcome after AKI appeared more when CR and TR diets were commenced during exercise. The reduction of lipid profile changes was more pronounced in the group that received CR diet during exercise.

The brain neuropeptides and STAT3 mediate the inhibitory effect of 17-ß Estradiol on central leptin resistance in young but not aged female high-fat diet mice.

Aging and menopause effect on body composition and energy balance. Estrogen (E2) plays an important role in body's metabolism. The aim of the present study was to determine changes in leptin function in young intact and ovariectomized (OVX) animals in comparison to the aged animals treated with E2. Young (Intact and OVX 4 months) and aged (19-21 months) female mice were fed High-fat diet (HFD) for 12 weeks and, then they were divided into eight groups including: Intact + OIL, Intact + E2, Intact + Pair body weight (PBW), OVX + OIL, OVX + E2, OVX + PBW, Aged + OIL, and Aged + E2. E2 was administered subcutaneously every four days for four weeks. Responsiveness to leptin was assessed by measuring energy balance components. Results showed that eating HFD increased weight and calorie consumption in young mice, and chronic treatment with E2 decreased both these variables in young animals. E2 only improved the sensitivity to leptin in young animals. Treatment with E2 resulted in increased α-MSH neuropeptide, reduced NPY and AgRP neuropeptides in the brain, and decreased serum leptin in the young animals. Also, treatment with E2 increased the expression of p-STAT3 molecular level in the hypothalamic arcuate nucleus (ARC) in the young animals. Our results indicated that response to E2 depended on age and E2 protects young HFD fed mice from obesity and improves leptin sensitivity.

Protective effects of early exercise on neuroinflammation, and neurotoxicity associated by traumatic brain injury: a behavioral and neurochemical approach.

OBJECTIVE: The benefits of exercise in TBI have been proven. However, the time-dependent effects of exercise initiation and the involved mechanisms are controversial. We investigated the effects of preconditioning, continuous, early, and delayed treadmill exercise on motor behavior, brain edema, inflammation, and oxidative stress in experimental traumatic brain injury (TBI). MATERIALS AND METHODS: 48 male rats were assigned into two groups: sedentary control (Sham and TBI) and exercise groups: 1MB (preconditioning, initiation beginning at 1 month before trauma), 1MBA (continuous, initiation beginning at 1 month before and continuing 1 month after trauma), 24hA (early, initiation beginning at 24 h after trauma), and 1WA (delay, initiation beginning at 1 week after trauma). The rats in exercise groups were forced to run on a treadmill five days a week for 30 min per day. Rotarod and open file were used to assess motor behavior. ELISA was also used to measure total antioxidant capacity (TAC), tumor necrosis factor-alpha (TNF-α), and malondialdehyde (MDA) in serum and CSF. RESULTS: Exercise significantly decreased neurological impairments, motor deficits, and apoptosis compared with the sedentary group. Early (within 24 h) and ongoing (1 MBA) exercise significantly improved motor behavior after TBI. In addition, these exercise programs inhibited brain edema and the number of apoptotic cells. MDA and TNF-α levels increased in all exercise groups, but the effects were greater after early exercise than after delayed exercise, resulting in a significant decrease in TAC levels in serum and CSF. We discovered a positive correlation between MDA, TAC, and TNF-α concentration in serum and CSF. CONCLUSION: Our finding suggests that early exercise (24hA) and 1MBA groups afford neuroprotection and reduce the second injury consequence, probably by reducing neuronal apoptosis and oxidative stress.

Spiritual Well-being in Patients with Chronic Diseases: A Systematic Review and Meta-analysis.

As a significant health challenge, chronic disease can have critical spiritual consequences for patients. Therefore, the study of spiritual well-being as an aspect of health is essential but has been less considered with regard to chronic diseases. Thus, this systematic review and meta-analysis were conducted to investigate spiritual well-being in patients with chronic diseases. For this purpose, in the initial search that was performed of valid databases, a total of 615 descriptive studies published between 2000 and 2018 were found. After carefully assessing these, only 24 studies were included in the review. Overall, the spiritual well-being of 3289 patients with chronic disease was investigated. This study showed that the total mean score of the spiritual well-being of patients with chronic diseases was 86.65 (P < 0.001, 95%, CI: 80.34-92.96), indicating a moderate level of spiritual well-being in these patients. Thus, patients with chronic diseases are recommended to consider spiritual consultation programs.

Activators of SIRT1 in the kidney and protective effects of SIRT1 during acute kidney injury (AKI) (effect of SIRT1 activators on acute kidney injury).

Acute kidney injury (AKI) is a complex disorder and a clinical condition characterized by acute reduction in renal function. If AKI is not treated, it can lead to chronic kidney disease, which is associated with a high risk of death. SIRT1 (silent information regulator 1) is an NAD-dependent deacetylase. This enzyme is responsible for the processes of DNA repair or recombination, chromosomal stability, and gene transcription. This enzyme also plays a protective role in many diseases, including AKI. In this study, we review the mechanisms that mediate the protective effects of SIRT1 on AKI, including SIRT1 activators.

The Hepatoprotective mechanisms of 17ß-estradiol after traumatic brain injury in male rats: Classical and non-classical estrogen receptors.

Protective effects of estrogen (E2) on traumatic brain injury (TBI) have been determined. In this study, the hepatoprotective effects of E2 after TBI through its receptors and oxidative stress regulation have been evaluated. Diffuse TBI induced by the Marmarou method in male rats. G15, PHTPP, MPP, and ICI182-780 as selective antagonists of E2 were injected before TBI. The results indicated that TBI induces a significant increase in liver enzymes [Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Glutamyl transferase (GGT)], and oxidants levels [Malondialdehyde (MDA), Nitric oxide (NO)] and decreases in antioxidant biomarkers [Glutathione peroxidase (GPx) and Superoxide dismutase (SOD)] in the brain and liver, and plasma. We also found that E2 significantly preserved levels of these biomarkers and enzymatic activity. All antagonists inhibited the effects of E2 on increasing SOD and GPx. Also, the effects of E2 on brain MDA levels were inhibited by all antagonists, but in the liver, only ICI + G15 + E2 + TBI group was affected. The impacts of E2 on brain and liver and plasma NO levels were inhibited by all antagonists. The current findings demonstrated that E2 probably improved liver injury after TBI by modulating oxidative stress. Also, both classic (ERß, ERα) and non-classic [G protein-coupled estrogen receptor (GPER)] receptors are affected in the protective effects of E2.

Acidified Nitrite Accelerates Wound Healing in Type 2 Diabetic Male Rats: A Histological and Stereological Evaluation.

Impaired skin nitric oxide production contributes to delayed wound healing in type 2 diabetes (T2D). This study aims to determine improved wound healing mechanisms by acidified nitrite (AN) in rats with T2D. Wistar rats were assigned to four subgroups: Untreated control, AN-treated control, untreated diabetes, and AN-treated diabetes. AN was applied daily from day 3 to day 28 after wounding. On days 3, 7, 14, 21, and 28, the wound levels of vascular endothelial growth factor (VEGF) were measured, and histological and stereological evaluations were performed. AN in diabetic rats increased the numerical density of basal cells (1070 ± 15.2 vs. 936.6 ± 37.5/mm3) and epidermal thickness (58.5 ± 3.5 vs. 44.3 ± 3.4 µm) (all p < 0.05); The dermis total volume and numerical density of fibroblasts at days 14, 21, and 28 were also higher (all p < 0.05). The VEGF levels were increased in the treated diabetic wounds at days 7 and 14, as was the total volume of fibrous tissue and hydroxyproline content at days 14 and 21 (all p < 0.05). AN improved diabetic wound healing by accelerating the dermis reconstruction, neovascularization, and collagen deposition.

The Changes of Brain Edema and Neurological Outcome, and the Probable Mechanisms in Diffuse Traumatic Brain Injury Induced in Rats with the History of Exercise.

Since no definitive treatment has been suggested for diffuse traumatic brain injury (TBI), and also as the effect of exercise has been proven to be beneficial in neurodegenerative diseases, the effect of endurance exercise on the complications of TBI along with its possible neuroprotective mechanism was investigated in this study. Our objective was to find out whether previous endurance exercise influences brain edema and neurological outcome in TBI. We also assessed the probable mechanism of endurance exercise effect in TBI. Rats were randomly assigned into four groups of sham, TBI, exercise + sham and exercise + TBI. Endurance exercise was carried out before TBI. Brain edema was assessed by calculating the percentage of brain water content 24 h after the surgery. Neurological outcome was evaluated by obtaining veterinary coma scale (VCS) at - 1, 1, 4 and 24 h after the surgery. Interleukin-1ß (IL-1ß), total antioxidant capacity (TAC), malondialdehyde (MDA), protein carbonyl and histopathological changes were evaluated 24 h after the surgery. Previous exercise prevented the increase in brain water content, MDA level, histopathological edema and apoptosis following TBI. The reduction in VCS in exercise + TBI group was lower than that of TBI group. In addition, a decrease in the level of serum IL-1ß and the content of brain protein carbonyl was reported in exercise + TBI group in comparison with the TBI group. We suggest that the previous endurance exercise prevents brain edema and improves neurological outcome following diffuse TBI, probably by reducing apoptosis, inflammation and oxidative stress.

Acidified nitrite improves wound healing in type 2 diabetic rats: Role of oxidative stress and inflammation.

PURPOSE: Decreased nitric oxide bioavailability in skin contributes to impaired wound healing in type 2 diabetes (T2D). This study aims at determining effects of acidified nitrite on wound closure as well as inflammatory and antioxidants markers in wound tissue of rats with T2D. MAIN METHODS: Skin wound was made on the back of rats 28 days after the induction of T2D (high-fat diet/low-dose of streptozotocin). Control and diabetic rats were subdivided into two subgroups: Untreated control (C), acidified nitrite-treated control (CN), untreated diabetes (D), and acidified nitrite-treated diabetes (DN). Acidified nitrite was applied once daily from day 3 to day 28 and the wounds were photographed for macroscopic changes. On days 3, 7, 14, 21, and 28 after wounding, wound levels of inflammatory and antioxidant markers were measured. RESULTS: Half closure time (CT50%) was significantly lower in acidified nitrite-treated diabetic rats compared to untreated ones (5.1 vs. 8.0 days, P < 0.001). Inflammatory response was delayed in diabetic rats and persistent inflammatory response was observed at day 14 after wounding. Acidified nitrite application restored the inflammatory response and antioxidant levels to control values. CONCLUSIONS: Acidified nitrite accelerated wound healing in rats with T2D by restoring delayed inflammatory response and augmentation of antioxidant defense.

CD36 gene polymorphism rs1761667 (G > A) is associated with hypertension and coronary artery disease in an Iranian population.

BACKGROUND: CD36 is associated with regulation of lipid metabolism, atherosclerosis, and blood pressure. Moreover, its variation may be involved in the development of hypertension and/or coronary artery disease (CAD). The present study was conducted to investigate the possible association of CD36 rs1761667 (G > A) polymorphism with hypertension and/or CAD in the southeastern of Iran. METHODS: The present observational study was composed of 238 subjects who were admitted for coronary angiography, and divided into four groups: 1) hypertensive without CAD (H-Tens, n = 52); 2) hypertensive with CAD (CAD + H-Tens, n = 57); 3) CAD without hypertension (CAD, n = 65); and 4) non-hypertensive without CAD as the control group (Ctrl, n = 64). The CD36 rs1761667 polymorphism was genotyped with PCR-RFLP method. Association between CD36 rs1761667 genotypes and the risk of CAD and hypertension was assessed using multinomial regression by adjusting for age, sex, creatinine, fasting blood sugar (FBS), systolic blood pressure (SBP) and diastolic blood pressure (DBP). RESULTS: In the present study, minor allele (A) frequency was 0.36. The genotype, but not allele frequency of the CD36 rs1761667 was significantly different between the four study groups (p = 0.003). Furthermore, using a recessive inheritance model CD36 rs1761667 polymorphism was significantly associated with an increased risk of CAD with hypertension (OR = 5.677; 95% CI = 1.053-30.601; p = 0.043). However, using the dominant model of CD36 rs1761667 had a protective effect on H-Tens and CAD patients. CONCLUSION: The present findings revealed an association between CD36 rs1761667 polymorphism and susceptibility to hypertension and/or CAD in a southeastern Iranian population.

Downregulation of IL-22 can be considered as a risk factor for onset of type 2 diabetes.

There is some controversy as for the roles played by tumor growth factor-ß (TGF-ß), interleukin-1ß (IL-1ß), and IL-22 in the onset process of type 2 diabetes (T2D). The main aim of this project was to examine serum levels of TGF-ß, IL-1ß, and IL-22 in the new cases and long period T2D patients as well as healthy controls. In this study, 115 new T2D patient cases (group 1), 434 T2D patients who have suffered from the disease more than 2 years (group 2), and 104 healthy controls have been selected from 6240 (3619 females) patients who were under study population from Kerman Coronary Artery Disease Risk Factor Study. Serum levels of TGF-ß, IL-1ß, and IL-22 have been evaluated using commercial kits. Serum levels of TGF-ß and IL-1ß significantly increased, while IL-22 decreased in 2 groups in comparison to healthy controls. Serum levels of IL-22, but not TGF-ß and IL-1ß, were significantly decreased in group 1 in comparison to healthy controls. There were no significant differences between groups 1 and 2 as for the cytokine levels. Serum levels of IL-22 increased in the females in group 2 when compared to females in group 1. It appears that TGF-ß and IL-1ß participate in the induction of inflammation after establishment of T2D, while decrease in IL-22 may be considered as a key factor for onset of the disease. Gender can also be considered as the main risk factor for variation in cytokine levels.

Does the administration of melatonin during post-traumatic brain injury affect cytokine levels?

Increased levels of inflammatory cytokines after traumatic brain injury (TBI) can lead to brain edema and neuronal death. In this study, the effect of melatonin on pro-inflammatory (IL-1ß, IL-6, and TNF-α) and anti-inflammatory (IL-10) cytokines following TBI was investigated considering anti-inflammatory effect of melatonin. Male Wistar rats were divided into five groups: Sham, TBI, TBI + VEH (vehicle), TBI + 5 mg dose of melatonin (MEL5), TBI + 20 mg dose of melatonin (MEL20). Diffuse TBI was induced by Marmarou method. Melatonin was administered 1, 24, 48 and 72 h after TBI through i.p. Brain water content and brain levels of pro-inflammatory (IL-1ß, IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines were measured 72 h after TBI. The IL-1ß levels decreased in the TBI + MEL5 and TBI + MEL20 groups in comparison to TBI + VEH group (p < 0.001). The levels of IL-6 and TNF-α also decreased in melatonin-treated groups compared to control group (p < 0.001). The amount of IL-10 decreased after TBI. But melatonin administration increased the IL-10 levels in comparison with TBI + VEH group (p < 0.001). The results showed that melatonin administration affected the brain levels of pro-inflammatory and anti-inflammatory cytokines involving in brain edema led to neuronal protection after TBI.

Characterization of the CA1 pyramidal neurons in rat model of hepatic cirrhosis: insights into their electrophysiological properties.

Although the key contributors of altering neurological function in hepatic encephalopathy are relatively well known, the electrophysiological mechanism of CA1 damage, a key vulnerable area during hyperammonemia, have not yet been defined. Therefore, here we focus on the electrophysiological mechanisms of cognitive impairments following bile duct ligation (BDL). We performed patch-clamp recordings from the CA1 pyramidal neurons in hippocampus of male Wistar rats, which underwent sham or BDL surgery. A striking electrophysiological change of hippocampal neurons in experimental model of BDL was observed in the present study. Spontaneous firing frequency and rate of action potential (AP) rebound was decreased and afterhyperpolarization amplitude (AHP) was increased significantly in hippocampal cells of BDL animals compared to sham group. Together, the results suggest that altered intrinsic properties of the hippocampal neurons may contribute to the cognitive abnormalities during hepatic encephalopathy (HE), highlighting the electrophysiological mechanisms for providing new treatments against HE.