Molecular Study of the Protective Effect of a Low-Carbohydrate, High-Fat Diet against Brain Insulin Resistance in an Animal Model of Metabolic Syndrome.

Brain insulin resistance is linked to metabolic syndrome (MetS). A low-carbohydrate, high-fat (LCHF) diet has been proposed to have a protective effect. Therefore, this study aimed to investigate the brain insulin resistance markers in a rat animal model of MetS and the protective effects of the LCHF diet. Four groups of male rats (10/group) were created. Group I (Control) was fed a regular diet. Groups II-IV were injected with dexamethasone (DEX) to induce MetS. Group II received DEX with a regular diet. Group III (DEX + LCHF) rates were fed a low-carbohydrate, high-fat diet, while Group IV (DEX + HCLF) rats were fed a high-carbohydrate, low-fat (HCLF) diet. At the end of the four-week experiment, HOMA-IR was calculated. Moreover, cerebral gene expression analysis of S-100B, BDNF, TNF-α, IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, Bax, Bcl-2, and caspase-3 was carried out. In the DEX group, rats showed a significant increase in the HOMA-IR and a decrease in the gene expression of IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, BDNF, and Bcl2, with a concomitant rise in S100B, TNF-α, Bax, and caspase-3. The LCHF diet group showed a significantly opposite effect on all parameters. In conclusion, MetS is associated with dysregulated cerebral gene expression of BDNF, S100B, and TNF-α and disturbed IGF-1 signaling, with increased apoptosis and neuroinflammation. Moreover, the LCHF diet showed a protective effect, as evidenced by preservation of the investigated biochemical and molecular parameters.

Insulin Resistance and Hypertension: Mechanisms Involved and Modifying Factors for Effective Glucose Control.

Factors such as aging, an unhealthy lifestyle with decreased physical activity, snacking, a standard Western diet, and smoking contribute to raising blood pressure to a dangerous level, increasing the risk of coronary artery disease and heart failure. Atherosclerosis, or aging of the blood vessels, is a physiological process that has accelerated in the last decades by the overconsumption of carbohydrates as the primary sources of caloric intake, resulting in increased triglycerides and VLDL-cholesterol and insulin spikes. Classically, medications ranging from beta blockers to angiotensin II blockers and even calcium channel blockers were used alone or in combination with lifestyle modifications as management tools in modern medicine to control arterial blood pressure. However, it is not easy to control blood pressure or the associated complications. A low-carbohydrate, high-fat (LCHF) diet can reduce glucose and insulin spikes, improve insulin sensitivity, and lessen atherosclerosis risk factors. We reviewed articles describing the etiology of insulin resistance (IR) and its impact on arterial blood pressure from databases including PubMed, PubMed Central, and Google Scholar. We discuss how the LCHF diet is beneficial to maintaining arterial blood pressure at normal levels, slowing down the progression of atherosclerosis, and reducing the use of antihypertensive medications. The mechanisms involved in IR associated with hypertension are also highlighted.

In Rats, Whole and Refined Grains Decrease Bone Mineral Density and Content through Modulating Osteoprotegerin and Receptor Activator of Nuclear Factor Kappa B.

Wheat is a staple grain in most parts of the world and is also frequently used in livestock feed. The current study looked at the impact of a wheat grain diet on bone turnover markers. Thirty male rats (n = 10) were separated into three groups of ten. The rats in Group 1 were fed a chow diet, while the rats in Group 2 were provided whole grains. The rats in Group 3 were fed refined grains. Each rat's bone mineral content (BMC) and bone mineral density (BMD) were measured after 12 weeks in the tibia of the right hind limb. We also looked at the amounts of bone turnover indicators in the blood. TRAP-5b (Tartrate-resistant acid Phosphatase 5b), NTx (N-telopeptide of type I collagen), DPD (deoxypyridinoline), alkaline phosphatase (ALP), and osteocalcin (OC), as well as the levels of Receptor Activator of Nuclear Factor Kappa B (RANK) and osteoprotegerin (OPG). Rats fed whole and refined grains showed lower BMC and BMD (p < 0.05) than the control group rats. The grain diet resulted in lower OPG, OC, and ALP levels than the chow-fed rats, as well as significantly higher (p < 0.05) levels of RANK, DPD, TRAB 5b, and NTx. In a rat model, an exclusive whole or refined grain diet lowered bone turnover and mass.

Atrazine Toxicity: The Possible Role of Natural Products for Effective Treatment.

There are various herbicides which were used in the agriculture industry. Atrazine (ATZ) is a chlorinated triazine herbicide that consists of a ring structure, known as the triazine ring, along with a chlorine atom and five nitrogen atoms. ATZ is a water-soluble herbicide, which makes it capable of easily infiltrating into majority of the aquatic ecosystems. There are reports of toxic effects of ATZ on different systems of the body but, unfortunately, majority of these scientific reports were documented in animals. The herbicide was reported to enter the body through various routes. The toxicity of the herbicide can cause deleterious effects on the respiratory, reproductive, endocrine, central nervous system, gastrointestinal, and urinary systems of the human body. Alarmingly, few studies in industrial workers showed ATZ exposure leading to cancer. We embarked on the present review to discuss the mechanism of action of ATZ toxicity for which there is no specific antidote or drug. Evidence-based published literature on the effective use of natural products such as lycopene, curcumin, Panax ginseng, Spirulina platensis, Fucoidans, vitamin C, soyabeans, quercetin, L-carnitine, Telfairia occidentalis, vitamin E, Garcinia kola, melatonin, selenium, Isatis indigotica, polyphenols, Acacia nilotica, and Zingiber officinale were discussed in detail. In the absence of any particular allopathic drug, the present review may open the doors for future drug design involving the natural products and their active compounds.

Low-Carbohydrate Ketogenic Diet for Improvement of Glycemic Control: Mechanism of Action of Ketosis and Beneficial Effects.

The incidence of metabolic syndrome and diabetes mellitus is increasing globally. A diet rich in carbohydrates increases the hyperglycemic state. While considering the lifestyle changes to combat life-threatening diseases, there is an effort to decrease the daily intake of carbohydrates. A low-carbohydrate diet also makes the body rely more on fat for energy, so there is less fat accumulation. A diet is considered to be low-carbohydrate ketogenic if the intake is ≤ 50 g per day. The 'low -carbohydrate ketogenic diet' (LCKD) produces ketosis. LCKD contains high-fat, moderateprotein, and low-carbohydrate components. The main objectives of the present review are to discuss insulin resistance in different viscera of the body, describe the role of adipokines in insulin resistance, understand the mechanism of ketogenesis, and determine the impact of LCKD in overcoming insulin resistance in the body. In the present review, we also highlight the beneficial effects of LCKD in metabolic, neurodegenerative, cardiovascular, and lipid disorders and discuss the effect on longevity and aging. LCKD may help in combating the morbidity and mortality arising from the above-mentioned diseases and also help in leading a better quality of life.

Resveratrol Modulates Bone Mineral Density and Bone Mineral Content in A Rat Model of Male Hypogonadism.

OBJECTIVE: To determine whether resveratrol (Res) can correct osteoporosis induced in a rat model of male hypogonadism. METHODS: Thirty-two rats were randomly divided into 4 groups, 8 in each group; 1) a control sham group: underwent a similar surgical procedure for induction of orchiectomy (ORCD) without ligation of any arteries or veins or removal of the testis and epididymis; 2) a control + Res-treated group (Con+Res): underwent sham surgery similar to the control, but was then treated with Res, as described below; 3) an ORCD-induced group: bilateral ORCD surgery as described above, and 4) a ORCD+Res-treated group: bilateral ORCD surgery followed by Res treatment. Res treatment began 4 weeks after ORCD and continued for 12 weeks. After 12 weeks, bone mineral density (BMD) and bone mineral content (BMC) were measured in the tibia and femur of each rat's right hind leg. Blood levels of bone turnover indicators such as deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTX I), alkaline phosphatase (ALP), and osteocalcin (OC), as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG) were assessed. RESULTS: ORCD significantly decreased BMD (P<0.01) and significantly increased bone resorption, manifested by increased RANK. In addition, it inhibited serum levels of OPG and OC. Res treatment after ORCD effectively increased serum levels of bone formation markers such as OPG and OC, compared with testisectomized rats (P<0.05). CONCLUSION: Res could ameliorate bone loss induced by male hypogonadism, possible via restoration of the normal balance between RANK and OPG.

Low-Carbohydrate High-Fat Diet: A SWOC Analysis.

Insulin resistance (IR) plays a role in the pathogenesis of many diseases, such as type 2 diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, obesity, and neurodegenerative diseases, including Alzheimer's disease. The ketogenic diet (KD) is a low-carbohydrate/high-fat diet that arose in the 1920s as an effective treatment for seizure control. Since then, the KD has been studied as a therapeutic approach for various IR-related disorders with successful results. To date, the use of the KD is still debatable regarding its safety. Some studies have acknowledged its usefulness, while others do not recommend its long-term implementation. In this review, we applied a SWOC (Strengths, Weaknesses, Opportunities, and Challenges) analysis that revealed the positive, constructive strengths of the KD, its potential complications, different conditions that can make used for it, and the challenges faced by both physicians and subjects throughout a KD. This SWOC analysis showed that the KD works on the pathophysiological mechanism of IR-related disorders such as chronic inflammation, oxidative stress and mitochondrial stress. Furthermore, the implementation of the KD as a potential adjuvant therapy for many diseases, including cancer, neurodegenerative disorders, polycystic ovary syndrome, and pain management was proven. On the other hand, the short and long-term possible undesirable KD-related effects, including nutritional deficiencies, growth retardation and nephrolithiasis, should be considered and strictly monitored. Conclusively, this review provides a context for decision-makers, physicians, researchers, and the general population to focus on this dietary intervention in preventing and treating diseases. Moreover, it draws the attention of scientists and physicians towards the opportunities and challenges associated with the KD that requires attention before KD initiation.

Natural Products in Mitigation of Bisphenol A Toxicity: Future Therapeutic Use.

Bisphenol A (BPA) is a ubiquitous environmental toxin with deleterious endocrine-disrupting effects. It is widely used in producing epoxy resins, polycarbonate plastics, and polyvinyl chloride plastics. Human beings are regularly exposed to BPA through inhalation, ingestion, and topical absorption routes. The prevalence of BPA exposure has considerably increased over the past decades. Previous research studies have found a plethora of evidence of BPA's harmful effects. Interestingly, even at a lower concentration, this industrial product was found to be harmful at cellular and tissue levels, affecting various body functions. A noble and possible treatment could be made plausible by using natural products (NPs). In this review, we highlight existing experimental evidence of NPs against BPA exposure-induced adverse effects, which involve the body's reproductive, neurological, hepatic, renal, cardiovascular, and endocrine systems. The review also focuses on the targeted signaling pathways of NPs involved in BPA-induced toxicity. Although potential molecular mechanisms underlying BPA-induced toxicity have been investigated, there is currently no specific targeted treatment for BPA-induced toxicity. Hence, natural products could be considered for future therapeutic use against adverse and harmful effects of BPA exposure.

Location-Linked QR Code as a Safe Tool for Recording Classroom Attendance During COVID-19 Pandemic: Perspectives of Medical Students.

COVID-19 lockdowns affected educational programs. Online learning has suddenly become the main form of medical education. However, attendance enhances a student's competency and professionalism. Rising student numbers and the COVID-19 pandemic make in-class learning challenging. This study investigates medical students' perceptions of a recently implemented tool for recording attendance using a QR code that detects students' location while scanning. An online questionnaire was designed to collect responses. One hundred thirty-two students completed the survey. Students agreed that the method was usable, reliable, accurate, secure, and convenient. This method should be investigated as a standard tool for attendance recording. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01625-7.

Modulation of Dyslipidemia Markers Apo B/Apo A and Triglycerides/HDL-Cholesterol Ratios by Low-Carbohydrate High-Fat Diet in a Rat Model of Metabolic Syndrome.

Metabolic syndrome (MetS) risks cardiovascular diseases due to its associated Dyslipidemia. It is proposed that a low-carbohydrate, high-fat (LCHF) diet positively ameliorates the MetS and reverses insulin resistance. Therefore, we aimed to investigate the protecting effect of the LCHF diet on MetS-associated Dyslipidemia in an experimental animal model. Forty male Sprague-Dawley rats were divided into four groups (10/group): the control group, dexamethasone-induced MetS (DEX) (250 µg/kg/day), LCHF-fed MetS group (DEX + LCHF), and High-Carbohydrate-Low-Fat-fed MetS group (DEX + HCLF). At the end of the four-week experiment, fasting glucose, insulin, lipid profile (LDL-C, HDL-C, Triglyceride), oxidized-LDL, and small dense-LDL using the ELISA technique were estimated. HOMA-IR, Apo B/Apo A1 ratio, and TG/HDL were calculated. Moreover, histological examination of the liver by H & E and Sudan III stain was carried out. In the DEX group, rats showed a significant (p < 0.05) increase in the HOMA-IR, atherogenic parameters, such as s-LDL, OX-LDL, Apo B/Apo A1 ratio, and TG/HDL. The LCHF diet significantly improved the parameters of Dyslipidemia (p < 0.05) by decreasing the Apo B/Apo A1 and TG/HDL-C ratios. Decreased steatosis in LCHF-fed rats compared to HCLF was also revealed. In conclusion, the LCHF diet ameliorates MetS-associated Dyslipidemia, as noted from biochemical results and histological examination.

Effect of Intermittent Fasting on Glucose Homeostasis and Bone Remodeling in Glucocorticoid-Induced Osteoporosis Rat Model.

BACKGROUND: The present study examined the effect of intermittent fasting (IF) on bone mineral content (BMC) and bone mineral density (BMD) and the markers of bone remodeling in a glucocorticoid-induced osteoporosis (GIO) rat model. METHODS: Forty male rats were allocated to 4 groups (N=10 per group): control group of normal rats; control+IF group (normal rats subjected to IF for 16-18 hr daily for 90 days); dexamethasone (DEX) group: (DEX [0.5 mg i.p.] for 90 days); and DEX+IF group (DEX and IF for 90 days). By the end of the experiment, BMD and BMC in the right tibia were measured. Serum levels of the following were measured: glucose; insulin; triglycerides (TGs); total cholesterol; parathyroid hormone (PTH); osteoprotegerin (OPG); receptor activator of nuclear factor-κB (RANK); bone-resorbing cytokines, including bone deoxypyridinoline (DPD), N-terminal telopeptide of collagen type I (NTX-1), and tartrate-resistant acid phosphatase 5b (TRAP-5b); and bone-forming cytokines, including alkaline phosphatase (ALP) and osteocalcin (OC). RESULTS: DEX administration for 90 days resulted in significantly increased serum levels of glucose, insulin, TGs, cholesterol, PTH, OPG, DPD, NTX-1, and TRAP-5b and significantly decreased BMD, BMC, and serum levels of RANK, OC, and ALP (all P<0.05). IF for 90 days significantly improved all these parameters (all P<0.05). CONCLUSIONS: IF corrected GIO in rats by inhibiting osteoclastogenesis and PTH secretion and stimulating osteoblast activity.

MORTALITY DUE TO TRANSPORT ACCIDENTS IN THE CITY OF SÃO PAULO: 2005-2015.

OBJECTIVE: To characterize cases of land transport accidents in the macro-regions of city of São Paulo in 2005, 2010, and 2015. METHODS: This is a population-based, longitudinal and retrospective study of time series, based on a quantitative survey of land transport accidents that occurred in the city of São Paulo in 2005, 2010 and 2015 using data from the Mortality Information System of the City of São Paulo. RESULTS: A total of 1,343, 1,567 and 1,088 deaths by accident recorded in the city' population in the years 2005, 2010 and 2015 respectively. The highest occurrences were in the age groups 15 to 24 years and 24 to 34 years. The highest number of deaths due to accidents was among males. The mortality rates observed in the macro-regions were South (23.8%), East (22%), North (21.6%), West (7.1%), and Center (3%). In comparing the years examined, there was a decline in the mortality rate per 100,000 inhabitants in most macro-regions. CONCLUSION: Despite the decrease in overall accident mortality in most macro-regions, it still deserves attention on preventive traffic actions focused on young males living in peripheral neighborhoods, since they represent the most susceptible group. Level of evidence II; Retrospective Study.

OBJETIVO: Caracterizar os casos de acidentes de transporte terrestre nas macrorregiões do município de São Paulo nos anos de 2005, 2010 e 2015. MÉTODOS: Trata-se de estudo de base populacional, longitudinal e retrospectivo de séries temporais, embasado em um levantamento quantitativo dos acidentes de transporte terrestres ocorridos no município de São Paulo nos anos de 2005, 2010 e 2015, utilizando dados provenientes do Sistema de Informações sobre Mortalidade. RESULTADOS: Um total de 1.343, 1.567 e 1.088 óbitos por acidente foram registrados para a população do município nos anos de 2005, 2010 e 2015, respectivamente. A maior ocorrência se deu nas faixas etárias de 15 a 24 anos e 24 a 34 anos. O maior número de mortes por acidentes se deu no sexo masculino. As taxas de mortalidade observadas nas macrorregiões foram: Sul (23,8%), Leste (22%), Norte (21,6%), Oeste (7,1%) e Centro (3%). Comparando-se períodos, houve queda nos coeficientes padronizados de mortalidade geral por 100 mil habitantes na maioria das macrorregiões. CONCLUSÃO: Apesar da queda na mortalidade geral dos acidentes na maioria das macrorregiões, ela ainda merece atenção e foco em ações de trânsito preventivas direcionadas aos jovens do sexo masculino que residem em bairros periféricos, pois representam o grupo mais suscetível. Nível II - Estudo prognóstico - Investigação do efeito de características de um paciente sobre o desfecho da doença. Nível de Evidência II; Estudo retrospectivo.

Mortality due to transport accidents in the city of são paulo: 2005-2015 / Mortalidade por acidentes de transporte no município de são paulo: 2005-2015

ABSTRACT Objective: To characterize cases of land transport accidents in the macro-regions of city of São Paulo in 2005, 2010, and 2015. Methods: This is a population-based, longitudinal and retrospective study of time series, based on a quantitative survey of land transport accidents that occurred in the city of São Paulo in 2005, 2010 and 2015 using data from the Mortality Information System of the City of São Paulo. Results: A total of 1,343, 1,567 and 1,088 deaths by accident recorded in the city' population in the years 2005, 2010 and 2015 respectively. The highest occurrences were in the age groups 15 to 24 years and 24 to 34 years. The highest number of deaths due to accidents was among males. The mortality rates observed in the macro-regions were South (23.8%), East (22%), North (21.6%), West (7.1%), and Center (3%). In comparing the years examined, there was a decline in the mortality rate per 100,000 inhabitants in most macro-regions. Conclusion: Despite the decrease in overall accident mortality in most macro-regions, it still deserves attention on preventive traffic actions focused on young males living in peripheral neighborhoods, since they represent the most susceptible group. Level of evidence II; Retrospective Study.

RESUMO Objetivo: Caracterizar os casos de acidentes de transporte terrestre nas macrorregiões do município de São Paulo nos anos de 2005, 2010 e 2015. Métodos: Trata-se de estudo de base populacional, longitudinal e retrospectivo de séries temporais, embasado em um levantamento quantitativo dos acidentes de transporte terrestres ocorridos no município de São Paulo nos anos de 2005, 2010 e 2015, utilizando dados provenientes do Sistema de Informações sobre Mortalidade. Resultados: Um total de 1.343, 1.567 e 1.088 óbitos por acidente foram registrados para a população do município nos anos de 2005, 2010 e 2015, respectivamente. A maior ocorrência se deu nas faixas etárias de 15 a 24 anos e 24 a 34 anos. O maior número de mortes por acidentes se deu no sexo masculino. As taxas de mortalidade observadas nas macrorregiões foram: Sul (23,8%), Leste (22%), Norte (21,6%), Oeste (7,1%) e Centro (3%). Comparando-se períodos, houve queda nos coeficientes padronizados de mortalidade geral por 100 mil habitantes na maioria das macrorregiões. Conclusão: Apesar da queda na mortalidade geral dos acidentes na maioria das macrorregiões, ela ainda merece atenção e foco em ações de trânsito preventivas direcionadas aos jovens do sexo masculino que residem em bairros periféricos, pois representam o grupo mais suscetível. Nível II - Estudo prognóstico - Investigação do efeito de características de um paciente sobre o desfecho da doença. Nível de Evidência II; Estudo retrospectivo.

Whole and refined grains change behavior and reduce brain derived neurotrophic factor and neurotrophin-3 in rats.

In most of the world, wheat is one of the main staple foods, and is also widely used in livestock feed. In the current study, we investigated the effects of wheat grain consumption on the rat behavior and neurogenesis markers. Thirty male rats were divided into three equal groups (n = 10). Group 1 was the control group fed with chow diet (Carbohydrates 63%, fat 13% and protein 24%), the Group 2 rats were fed with whole grains and the Group 3 rats were fed with refined grains. After 12 weeks, we measured the hippocampal and prefrontal cortical brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), 5-hydroxytryptamine, dopamine, norepinephrine, malondialdehyde (MDA) and reduced glutathione (GSH) levels. Also, we evaluated the rat behavior by forced swimming test (FST) and elevated plus maze (EPM) test. Additionally, we measured serum level of glucose, lipid profile, insulin and cortisol. Weight gain at the end of the study was measured in each group. The rats on a diet of whole and refined grains had low BDNF, NT-3, norepinephrine, dopamine and serotonin significantly (p < .01) in both the hippocampus and prefrontal cortex as compared to control rats. Moreover, the MDA increased significantly with significant reduction in GSH versus the control rats. Moreover, in response to grain consumption, the performance in FST showed a significant (p < .01) shortage in the latency of the attempts to escape as well as a significant prolongation (p < .01) in behavioral immobility as compared to control rats with significant (p < .05) prolongation in time spent in closed arm in EPM. An exclusive diet of either whole or refined grain in a rat model induced anxiety and depressive behaviors and negatively affected the BDNF and NT-3 and modulated the level of the neurotransmitters with significant shift in their behavior. PRACTICAL APPLICATIONS: Grains are considered the major caloric source all over the world that may predispose to the development of chronic diseases. In this research, we evaluated the role of grains in modulating the rate of production of neurogenic factors in rats.

Chronic valproic acid administration enhances oxidative stress, upregulates IL6 and downregulates Nrf2, Glut1 and Glut4 in rat's liver and brain.

Valproic acid (VPA) is a powerful antiepileptic drug that was associated with several neurological and hepatic problems especially with increasing its dose and duration. These problems may be metabolic in origin and related to glucose homeostasis. So, the present study investigated the effect of different doses and durations of VPA on the expression of glucose transporters (Glut1 and Glut4), oxidative stress and inflammatory cytokine (IL-6) in the liver and specific brain regions. Seventy-two male Sprague-Dawley rats were randomly allocated into three equal groups: (1) saline group, (2) 200 mg VPA group and (3) 400 mg VPA group. By the end of experiments, the expressions of Glut1, Glut4 nuclear factor erythroid-like 2 related factor (Nrf2), IL-6 and oxidative stress markers [malondialdehyde (MDA) and glutathione (GSH)] in the liver, corpus striatum, prefrontal cortex (PFC) and cerebellum were assessed. We found that administration of VPA (200 mg and 400 mg) caused a significant decrease in the Glut1 and Glut4 expression in different tissues in a dose- and time-dependent manner (P < 0.01). Also, VPA (200 and 400 mg) caused a significant increase in MDA with a decrease in GSH in tissues at different times. Moreover, VPA (200 and 400 mg) caused significant upregulation in IL-6 expression and downregulation in Nrf2 expression (P < 0.01). The results suggest that increasing the dose and time of VPA therapy downregulates Glut1 and Glut4 in the liver and brain which may impair glucose uptake in these tissues. This effect was associated with enhanced oxidative stress, downregulation of nrf2 and upregulation of IL-6 in liver and brain tissues.

The Impact of Intermittent Fasting on Brain-Derived Neurotrophic Factor, Neurotrophin 3, and Rat Behavior in a Rat Model of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is known to be associated with an increased risk of dementia, specifically Alzheimer's disease and vascular dementia. Intermittent fasting (IF) has been proposed to produce neuroprotective effects through the activation of several signaling pathways. In this study, we investigated the effect of IF on rat behavior in type 2 diabetic rats. Forty male Wistar Kyoto rats were divided into four groups (n = 10 for each): the ad libitum (Ad) group, the intermittent fasting group (IF), the streptozotocin-induced diabetic 2 group (T2DM) fed a high-fat diet for 4 weeks followed by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) 25 mg kg-1, and the diabetic group with intermittent fasting (T2DM+IF). We evaluated the impact of 3 months of IF (16 h of food deprivation daily) on the levels of brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), serotonin, dopamine, and glutamate in the hippocampus, and rat behavior was assessed by the forced swim test and elevated plus maze. IF for 12 weeks significantly increased (p < 0.05) the levels of NT3 and BDNF in both control and T2DM rats. Additionally, it increased serotonin, dopamine, and glutamic acid in diabetic rats. Moreover, IF modulated glucose homeostasis parameters, with a significant decrease (p < 0.05) in insulin resistance and downregulation of serum corticosterone level. Interestingly, T2DM rats showed a significant increase in anxiety and depression behaviors, which were ameliorated by IF. These findings suggest that IF could produce a potentially protective effect by increasing the levels of BDNF and NT3 in both control and T2DM rats. IF could be considered as an additional therapy for depression, anxiety, and neurodegenerative diseases.

Impact of Dehydroepiandrosterone (DHEA) on Bone Mineral Density and Bone Mineral Content in a Rat Model of Male Hypogonadism.

OBJECTIVES: The present study examined the effect DHEA (dehydroepiandrosterone) on bone mineral content (BMC) and bone mineral density (BMD) and biomarkers of bone remodeling in orchidectomized male rats. MATERIAL AND METHODS: A total of 32 male rats were divided equally into four groups (n = 8): (i) control group (C), (ii) control treated with DHEA (Control + DHEA), (iii) orchidectomized (ORCH) group that underwent bilateral orchidectomy and (iv) orchidectomized (ORCH) rats treated with DHEA (ORCH+DHEA). DHEA treatment started 4 weeks after orchidectomy and continued for 12 weeks. After 12 weeks the bone mineral density (BMD) and bone mineral content (BMC) were assayed in the tibia and femur of the right hind limb of each rat. We also measured the serum levels of the bone turnover markers deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTx), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase 5b (TRAP-5b) and osteocalcin (OC) as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG). RESULTS: Orchidectomy in rats caused significant reduction in BMD, BMC, serum levels of testosterone, PTH (parathyroid hormone), OPG, OC and ALP with significant rise in serum levels of TRAP-5B, RANK, Dpd and NTx1 (p < 0.05). On the other hand, DHEA therapy for 12 weeks caused significant improvement in all studied parameters except NTx1 (p < 0.05). CONCLUSIONS: DHEA corrected hypogonadism-induced osteoporosis in male rats probably via inhibiting osteoclastogenesis, stimulating the activity of osteoblasts and stimulating the secretion of PTH and testosterone.

Melatonin Improves Memory Deficits in Rats with Cerebral Hypoperfusion, Possibly, Through Decreasing the Expression of Small-Conductance Ca2+-Activated K+ Channels.

This study investigated the expression pattern, regulation of expression, and the role of hippocampal small-conductance Ca2+-activated K+ (SK) channels in memory deficits after cerebral hypoperfusion (CHP) with or without melatonin treatment, in rats. Adults male Wistar rats (n = 20/group) were divided into (1) a sham (2) a sham + melatonin (3) a two-vessel occlusion (2-VO) model, and (4) a 2-VO + melatonin. Melatonin was administered (i.p.) to all rats at a daily dose of 10 mg kg-1 for 7 days starting at the time of 2-VO-induction. In contrast to 2-VO rats, melatonin increased the latency of the passive avoidance learning test and decreased time to find the hidden platform in Water Morris Test in all tested rats. In addition, it concomitantly downregulated SK1, SK2, and SK3 channels, downregulated mRNA levels of TNFα and IL-1ß, enhanced BDNF levels and activity of PKA levels, and restored the levels of cholinergic markers in the hippocampi of the treated-rats. Mechanistically, melatonin significantly prevented CHP-induced activation of ERK1/2, JNK, and P38 MAPK at least by inhibiting ROS generation and enhancing the total antioxidant potential. In cultured hypoxic hippocampal neurons, individual blockage of MAPK signaling by the MEK1/2 inhibitor (U0126), but not by the P38 inhibitor (SB203580) or JNK inhibitor (SP600125), completely prevented the upregulation of all three kinds of SK channels. These data clearly confirm that upregulation of SK channels plays a role in CHP-induced memory loss and indicate that melatonin reverses memory deficits after CHP in rats, at least by, downregulation of SK1, SK2, and SK3 channels in their hippocampi.

Swim exercise inhibits hemostatic abnormalities in a rat model of obesity and insulin resistance.

BACKGROUND: We sought to determine whether swim exercise can inhibit high carbohydrate and fat diet (HCFD)-induced biomarkers of coagulation and thrombosis. MATERIAL AND METHODS: Rats were either fed with HCFD (model group) or a standard laboratory chow (control group) for 15 weeks. Swim exercise-'treated' rats started swim exercise training from the 11th week until being sacrificed, on Week 15. RESULTS: HCFD caused a significant increase in blood glucose, insulin resistance (HOMA-IR), lipidemia, and inflammatory biomarkers. In addition, HCFD significantly modulated coagulation and thrombosis biomarkers; fibrinogen, plasminogen activator inhibitor-1, von Willebrand factor, prothrombin time, activated partial thromboplastin time, blood clotting and bleeding time, and ADP-induced platelet aggregation that was effectively inhibited by swimming exercises. CONCLUSIONS: We demonstrate that in an animal model of obesity and insulin resistance, there is a significant change in hemostasis, which is ameliorated by swim exercise.

Possible mechanisms underlying fatty liver in a rat model of male hypogonadism: A protective role for testosterone.

AIMS: To investigate the effects of testosterone (Test) deficiency and testosterone replacement therapy (TRT) on the development of non-alcoholic fatty liver disease (NAFLD) and associated peripheral insulin resistance (IR) in male rats and to illustrate the underlying mechanisms of action. MATERIALS AND METHODS: male Sprague Dawley rats were divided into 3 groups as follows: 1) sham-operated group (n = 11), 2) ORCD-induced group (n = 9) exposed to orchidectomy (ORCD), achieved by complete surgical removal of testicles, and 3) ORCD + Test treated group (n = 10) (11 ng/mL Test propionate, 3x/week, S.C.). RESULTS: Data revealed significant increases in final body, liver, visceral and subcutaneous fats weights with significant increases in fasting plasma glucose and insulin levels and HOMA-IR. Additionally, ORCD rats had higher UAC for measured glucose levels and insulin levels during OGTT and higher AUC for measured glucose levels during ITT. Interesting, higher serum and hepatic levels of TGs and CHOL and higher serum levels of LDL were seen in ORCD-induced rats. Mechanistically, significant increases in mRNA levels of SREBP-1, SREBP-2, ACC-1, FAS, HMGCOAR and HMGCOAS with significant increases in protein levels of both precursor and mature SREBP-1 and SREBP-2, PPAR-α, p-PPAR-α, CPT-1 and UCP-2 and significant lower protein levels p-AMPK and p-ACC-1 were detected in livers of ORCD rats. Test administration to ORCD-induced rats significantly ameliorated all of the above mentioned biochemical endpoints and reversed the effect of ORCD on mRNA and protein levels of these targets. In conclusion, Test deficiency could be an independent risk factor for the development of NAFLD by upregulation of lipid synthesis and disturb fatty acids oxidation whereas Test therapy is a protective strategy.