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.

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.

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.

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.

Effects of Herbs and Derived Natural Products on Lipopolysaccharide-Induced Toxicity: A Literature Review.

Introduction: Oxidative stress (OS) during inflammation can increase inflammatory responses and damage tissue. Lipopolysaccharide (LPS) can induce oxidative stress and inflammation in several organs. Natural products have several biological activities including anti-inflammatory, antioxidant, and immunoregulatory properties. The aims of the study are to study the possible therapeutic effects of natural products on LPS inducing toxicity on the nervous system, lung, liver, and immune system. Methods: The in vitro and in vivo research articles that were published in the last 5 years were included in the current study. The keywords included "lipopolysaccharide," "toxicity," "natural products," and "plant extract" were searched in different databases such as Scopus, PubMed, and Google Scholar until October 2021. Results: The results of most studies indicated that some medicinal herbs and their potent natural products can help to prevent, treat, and manage LPS-induced toxicity. Medicinal herbs and plant-derived natural products showed promising effects on managing and treating oxidative stress, inflammation, and immunomodulation by several mechanisms. Conclusion: However, these findings provide information about natural products for the prevention and treatment of LPS-induced toxicity, but the scientific validation of natural products requires more evidence on animal models to replace modern commercial medicine.

Protective effects of Portulaca oleracea and vitamin E on cardiovascular parameters in rats with subclinical hyperthyroidism.

INTRODUCTION: Subclinical hyperthyroidism (SHT) is an endocrine disorder that is associated with abnormalities in heart structure and function. Oxidative stress plays an important role in the pathophysiology of cardiac disorders caused by SHT. Portulaca oleracea (P. Oleracea) is a herbaceous plant with many pharmacologic effects including antioxidant, and anti-inflammatory properties. In the present study, the effects of Portulaca oleracea and vitamin E on the biochemical, hemodynamic, and functional parameters of the cardiac tissue was studied in rats with subclinical hyperthyroidism. METHODS: Fifty-six male rats were divided into seven groups: 1-Control group: daily injection of saline, 2-SHT group: daily injection of levothyroxine sodium (LS) (20 µg/kg), 3- T4+Po groups were given LS and P. oleracea (100, 200, and 400 mg/kg in drinking water), 4- the T4+vit E groups received LS and a daily injection of vitamin E (100 and 200 mg/kg). Cardiac index, systolic blood pressure (SBP), also malondialdehyde and total thiol levels were measured in cardiac tissue. RESULTS: SBP and maximum dP/dt were significantly increased and minimum dP/dt was significantly decreased in SHT group. In P. oleracea groups, maximum dP/dt were significantly reduced and minimum dP/dt was increased. Malondialdehyde levels and cardiac index in groups receiving vitamin E and P. oleracea were significantly decreased. Maximum dP/dt was decreased in the group receiving LS+vitamin E. Minimum dP/dt was significantly higher in group received LS+ vitamin E. CONCLUSION: This study showed that Portulaca oleracea has a positive effect on cardiac dysfunction caused by subclinical hyperthyroidism.

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.

The effect of HTLV1 infection on inflammatory and oxidative parameters in the liver, kidney, and pancreases of BALB/c mice.

Viral infections are linked to the progression of inflammatory reactions and oxidative stress that play pivotal roles in systemic diseases. To confirm this phenomenon, in the present study, TNF-α level and oxidative stress markers were examined in the liver, kidney, and pancreas of HTLV1-infected male BALB/c mice. To this end, twenty BALB/c mice were divided into HTLV1-infected mice that were inoculated with 1-million HTLV1-infected cells (MT-2), and the control groups. Two months after inoculation, the peripheral blood, mesenteric lymph nodes, liver, kidney, and pancreas were collected after deep anesthetization of mice (ketamine, 30 mg/kg). The extracted DNA of mesenteric lymph nodes was obtained to quantify proviral load (PVL) using quantitative real-time polymerase chain reaction (qRT-PCR). The levels of lipid peroxidation, total thiol (SH), nitric oxide (NO), TNF-α, catalase (CAT), and superoxide dismutase (SOD) activities were examined in the liver, kidney, and pancreases. Furthermore, histopathological changes in the liver and kidney were evaluated. In liver tissue, the levels of MDA, TNF-α, and blood cell infiltration were significantly increased, and the levels of CAT and SOD were significantly decreased. In the kidney, a reduction in SOD, CAT, and total SH and an increase in MDA and NO were observed. In the pancreas, CAT activity, total SH, and SOD were decreased, and the levels of MDA and NO were enhanced. In terms of TNF-α production, it has been shown that the level of this inflammatory cytokine was increased in the liver, kidney, and pancreas. The HTLV1 may have a role in inducing inflammatory reactions and oxidative stress pathways in the tissues.

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.

Human T-Cell Leukemia Virus Type 1 Changes Leukocyte Number and Oxidative Stress in the Lung and Blood of Female BALB/c Mice.

BACKGROUND: Human T-cell leukemia virus type 1(HTLV-1) infection is likely to induce nonneoplastic inflammatory pulmonary diseases. Therefore, an experimental study was conducted to evaluate the leukocytes' number alteration and oxidative stress in the lung and blood of HTLV-1-infected BALB/c mice, which could be of benefit for the recognition of HTLV-1 mechanism in the induction of pulmonary disorders. MATERIALS AND METHODS: Twenty female BALB/c mice were divided into two groups of control and HTLV-1-infected animals. The HTLV-1-infected group was inoculated with 106 MT-2 HTLV-1-infected cells. Two months later, the infection was confirmed using real-time polymerase chain reaction, and then lung pathological changes, total and differential inflammatory cell counts in the blood and bronchoalveolar lavage fluid (BALF), along with oxidative stress biomarker levels in the BALF and lung tissue were evaluated. RESULTS: In the HTLV-1-infected group, the peribronchitis score (P < 0.01), the number of total leukocytes, neutrophils, lymphocytes, and monocytes (P < 0.05) in the blood and BALF were increased. The number of eosinophils in the blood of the HTLV-1-infected group was higher than in the control group (P < 0.01), whereas the number of basophils of BALF was increased in the HTLV-1-infected group (P < 0.001). The lung and BALF oxidative stress results showed that the MDA level was increased, while the total thiol level and superoxide dismutase activity were decreased in the HTLV-1-infected group (P < 0.01). CONCLUSION: The HTLV-1 infection seems to induce pulmonary inflammatory reactions by recruiting leukocytes as well as inducing oxidative stress in the lung tissue.

A comprehensive review of long non-coding RNAs in the pathogenesis and development of non-alcoholic fatty liver disease.

One of the most prevalent diseases worldwide without a fully-known mechanism is non-alcoholic fatty liver disease (NAFLD). Recently, long non-coding RNAs (lncRNAs) have emerged as significant regulatory molecules. These RNAs have been claimed by bioinformatic research that is involved in biologic processes, including cell cycle, transcription factor regulation, fatty acids metabolism, and-so-forth. There is a body of evidence that lncRNAs have a pivotal role in triglyceride, cholesterol, and lipoprotein metabolism. Moreover, lncRNAs by up- or down-regulation of the downstream molecules in fatty acid metabolism may determine the fatty acid deposition in the liver. Therefore, lncRNAs have attracted considerable interest in NAFLD pathology and research. In this review, we provide all of the lncRNAs and their possible mechanisms which have been introduced up to now. It is hoped that this study would provide deep insight into the role of lncRNAs in NAFLD to recognize the better molecular targets for therapy.

The Role of Non-coding Genome in Cancer-associated Fibroblasts; Stateof- the-Art and Perspectives in Cancer Targeted Therapy.

Cancer-associated fibroblasts (CAFs) are senescent fibroblasts in tumor nest, which trigger a signaling center to remodel a desmoplastic tumor niche. CAF's functions in cancer are closely similar to myofibroblasts during the wound healing process. They can produce cytokines, enzymes, and protein- or RNA-containing exosomes to alter the function of surrounding cells. Non-- coding RNAs, including microRNAs and long non-coding RNAs, modulate pathologic mechanisms in cancer. Dysregulation of these RNAs influences the formation and function of CAFs. Furthermore, it has been demonstrated that CAFs, by releasing non-coding RNAs-containing exosomes, affect the tumor cells' behavior. CAFs also secrete mediators such as chemokines to alter the expression of non-coding RNAs in the tumor microenvironment. This study aimed to discuss the role of non-coding RNAs in CAF development in cancer. Additionally, we have shed light on the therapeutic approaches to develop the strategies based on the alteration of non-coding RNAs in cancer.

The role of myeloid-derived suppressor cells in rheumatoid arthritis: An update.

Rheumatoid arthritis (RA) is an autoimmune disease that generally affects the joints. In the late stages of the disease, it can be associated with several complications. Although the exact etiology of RA is unknown, various studies have been performed to understand better the immunological mechanisms involved in the pathogenesis of RA. At the onset of the disease, various immune cells migrate to the joints and increase the recruitment of immune cells to the joints by several immunological mediators such as cytokines and chemokines. The function of specific immune cells in RA is well-established. The shift of immune responses to Th1 or Th17 is one of the most essential factors in the development of RA. Myeloid-derived suppressor cells (MDSCs), as a heterogeneous population of myeloid cells, play a regulatory role in the immune system that inhibits T cell activity through several mechanisms. Various studies have been performed on the function of these cells in RA, which in some cases have yielded conflicting results. Therefore, the purpose of this review article is to comprehensively understand the pro-inflammatory and anti-inflammatory functions of MDSCs in the pathogenesis of RA.

The Role of Chemokines in Cardiovascular Diseases and the Therapeutic Effect of Curcumin on CXCL8 and CCL2 as Pathological Chemokines in Atherosclerosis.

Curcumin, as a vegetative flavonoid, has a protective and therapeutic role in various adverse states such as oxidative stress and inflammation. Remedial properties of this component have been reported in the different chronic diseases including cancers (myeloma, pancreatic, breast, colorectal), vitiligo, psoriasis, neuropathic pains, inflammatory disorders (osteoarthritis, uveitis, ulcerative colitis, Alzheimer), cardiovascular conditions, and diabetes.Cardiovascular disorders include atherosclerosis and various manifestations of atherosclerosis such as stroke, and myocardial infarction (MI) is the leading cause of mortality globally. Studies have shown varying expressions of inflammatory and non-inflammatory chemokines and chemokine receptors in cardiovascular disease, which have been highlighted first in this review. The alteration in chemokines secretion and chemokine receptors has an essential role in the pathophysiology of cardiovascular disease. Chemokines as cytokines with low molecular weight (8-12 kDa) mediate white blood cell (WBC) chemotactic reactions, vascular cell migration, and proliferation that induce endothelial dysfunction, atherogenesis, and cardiac hypertrophy.Several studies reported that curcumin could be advantageous in the attenuation of cardiovascular diseases via anti-inflammatory effects and redress of chemokine secretion and chemokine receptors. We present these studies with a focus on two chemokines: CXCL8 (IL-8) and CCL2 (chemoattractant protein 1 or MCP-1). Future research will further elucidate the precise potential of curcumin on chemokines in the adjustment of cardiovascular system activity or curcumin chemokine-based therapies.

The role of non-coding genome in the behavior of infiltrated myeloid-derived suppressor cells in tumor microenvironment; a perspective and state-of-the-art in cancer targeted therapy.

Cancer is one of the healthcare problems that affect many communities around the world. Many factors contribute to cancer development. Besides, these factors are counted as the main impediment in cancer immunotherapy. Myeloid-derived suppressor cells (MDSCs) are one of these impediments. MDSCs inhibit the immune responses through various mechanisms such as inhibitory cytokine release and nitric oxide metabolite production. Several factors are involved in forming these cells, including tumor secreted cytokine and chemokines, transcription factors, and non-coding RNA. In the meantime, micro-RNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the vital gene regulatory elements that affect gene expression. In this study, we are going to discuss the role of miRNAs and lncRNAs in MDSCs development in a cancer situation. It is hoped that miRNA and lncRNAs targeting may prevent the growth and development of these inhibitory cells in the cancer environment.

HTLV-1 infection-induced motor dysfunction, memory impairment, depression, and brain tissues oxidative damage in female BALB/c mice.

AIMS: The HTLV-1 infection is associated with a neuro-inflammatory disease. In the present study, the behavioral consequences and brain oxidative damages were evaluated in HTLV-1-infected BALB/c mice. MATERIAL AND METHODS: 20 female BALB/c mice were divided into two groups comprising control and HTLV-1-infected. The HTLV-1-infected group was inoculated with a 106 MT-2 HTLV-1-infected cell line. Two months later, the behavioral tests were conducted. Finally, oxidative stress was assessed in the cortex and hippocampus tissues. KEY FINDINGS: In the HTLV-1-infected group, running time and latency to fall, travel distance and time spent in the peripheral zone, total crossing number and total traveled distance in open field test, the latency of entrance into the dark compartment in the passive avoidance test, the new object exploration percentage, and discrimination ratio were significantly lower than in the control group. The immobility time, time spent in the dark compartment in passive avoidance test, and total exploration time significantly increased in the HTLV-1-infected group compared to the control group. In the cortical tissue of the HTLV-1 group, the malondialdehyde levels were elevated while the total thiol levels decreased in comparison to the control group. The activity of superoxide dismutase in the cortical and hippocampal tissues, and catalase activity in cortical tissue significantly decreased in the HTLV-1 group in comparison to the control group. SIGNIFICANCE: The HTLV-1 infection seems to induce depression-like behavior, motor dysfunction, disruption in working and fear memory and also oxidative stress in the cortex and hippocampus.