oxidative stress

Background: The unwanted adverse toxicity displayed by synthetic antidiabetic medicine leads to the search for effective natural medicine to combat diabetes complications. This study investigated the cardioprotective of Anacardium occidentale nuts methanolic in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats.Materials and methods: Forty male adult Wistar were used and fed with HFD for 6 weeks before diabetes induction. The rats were grouped into 5 groups, 8 rats/group. Group I: normal control; Group II: diabetic control; Group III & IV: diabetic rats + 100 mg/kgb.wt & 200 mg/kgb.wt Anacardium occidentale nuts methanolic extract; Group V: diabetic rats + 200 mg/kgb.wt metformin. The rats were sacrificed on the experiment’s last day, blood samples were collected and the hearts were isolated for biochemical parameters estimation.Results: Food intake, water intake, plasmas insulin, Fasting Blood Glucose (FBG), glycosylated hemoglobin (HbA1c), cardiac enzymes, lipid profile, inflammatory cytokines, malondialdehyde, fibrotic marker, caspase-3 in cardiac of diabetic rats were elevated (p < 0.05) significantly. Body weight, cardiac antioxidant, and anti-apoptotic marker levels diminished (p < 0.05) significantly in diabetic rats. 100 mg/kgb.wt & 200 mg/kgb.wt of Anacardium occidentale nuts methanolic extract administration significantly suppressed the plasma insulin, FBG, HbA1c, cardiac lipid profile, cardiac enzymes biomarker, cardiac inflammatory cytokines, cardiac malondialdehyde, cardiac fibrotic marker, cardiac caspase-3, food intake & water intake and increased the body weight, cardiac antioxidant & cardiac anti-apoptotic marker in the diabetic rats.Conclusion: Anacardium occidentale nuts attenuate cardiac injury in diabetes. It could be a natural medicine to manage diabetes-cardiovascular complications.

The N-hydroxydodecanamide (HA12) and its complexes tri-hydroxamato-iron(III) and di-hydroxamto-iron(III) chloride (HA8Fe3 and HA12Fe3Cl, respectively) showed antibacterial and antimycobacterial activities. The proteomic analysis demonstrated that the targets of Hydroxamic Acid (HA) and their complexes were involved in the biosynthesis of mycobacterial cell walls. The Reactive Oxygen Species (ROS) is one of the key elements to cause oxidative stress, damaging DNA, and cell membranes impaired during the procedure to kill bacteria. Here, the ROS production was determined to evaluate the compounds HA12, HA8Fe3, HA12Fe3Cl, and ZnCl2 against bacteria using 2’,7’-dichlorofluorescein diacetate (DCFDA) by spectrofluorometric analysis. The low fluorescence was observed using the compounds HA12, HA8Fe3, HA12Fe3Cl, and ZnCl2 treating the S. aureus and E. coli, indicating that the ROS production could not be observed using the compounds used at a dose higher than the Minimum Inhibitory Concentration (MIC). It was noted that the ROS determination could be performed with a concentration less than or equal to the MIC. This would enable the mechanism of action linked to the ROS production by HA and their metal complexes to be determined.

Background: Linagliptin is an anti-diabetic drug that claims no adverse effects and treatment of gestational diabetes mellitus (GDM) demands a safe anti-diabetic medication. Therefore, this study investigates the anti-diabetic efficacy of linagliptin in an induced GDM.Materials and methods: Thirty-two matured female rats (100 - 200 g) were utilized. Sixteen non-pregnant/diabetic animals were fed with a normal diet and sixteen rats were fed with a high-fat (HFD), mated at the estrous stage in 2:1, and pregnancy was confirmed with a spermatozoa in a vaginal smear. The pregnant rats were intraperitoneally injected with a single dose (30 mg/kgb. wt)of streptozotocin (STZ) to induce GDM. The animals were grouped into 4 groups, 8 rats/groups. Group I: control; Group II: control + 10 mg/kgb.wt linagliptin; Group III: GDM; Group IV: GDM + 10 mg/kgb.wt linagliptin. The animals were sacrificed after 14 days of treatment. Blood samples were collected for biochemical parameters.Results: Fasting blood glucose (FBG) insulin, glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), malondialdehyde (MDA), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels significant (p < 0.05) elevated in GDM rats, with significant reduction in high-density lipoprotein-cholesterol (HDL-C), catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH). Linagliptin administration significantly (p < 0.05) decreased the FBG, insulin, HbA1c, TC, TG, LDL-C, MDA, IL-6, IL-1β, and TNF-α and ameliorates the HDL-C, CAT, SOD, and GSH levels significantly.Conclusion: Linagliptin remarkably showed anti-hyperglycemic, anti-oxidative, and anti-inflammatory properties. Linagliptin could be a promising drug for hyperglycemia treatment during gestation.

Background: The impact of COVID-19 and long-term COVID-19 on gastrointestinal neoplasms remains underexplored. The current review investigates the potential link between these conditions and the role of gut microbiota in mediating oncogenic processes. Dysbiosis, characterized by alterations in gut microbial composition, may exacerbate inflammation and immune dysregulation, contributing to cancer development.Methods: A comprehensive literature review was conducted using databases including PubMed, Scopus, Embase, SciELO, and Web of Science. Inclusion criteria encompassed studies published between 2020 and 2024 that explored the intersection of COVID-19, long-term COVID-19, and gastrointestinal cancers. The articles were critically appraised for quality and relevance, and data were synthesized to elucidate common mechanisms and outcomes.Results: The review identifies several mechanisms by which gut microbiota may influence cancer risk in COVID-19 patients. Persistent inflammation, oxidative stress, and immune dysfunction observed in Long COVID were associated with dysbiosis. Specific microbial metabolites, such as secondary bile and short-chain fatty acids, were implicated in promoting tumorigenesis. Comparative analysis of studies suggests that SARS-CoV-2-induced dysbiosis may heighten susceptibility to gastrointestinal cancers, particularly in patients with prolonged post-infection symptoms.Conclusion: The findings underscore the need for further research to clarify the role of gut microbiota in cancer development among COVID-19 patients. These mechanisms could inform preventative strategies and therapeutic interventions, particularly for those experiencing COVID. The review highlights gaps in current knowledge and advocates for longitudinal studies to assess the long-term effects of COVID-19 on gastrointestinal health.

Treatment for HIV-associated neurocognitive disorders (HAND) remains elusive. 7,8-dihydroxyflavone (DHF), an analog of brain-derived neurotrophic factor (BDNF) and a high-affinity TrkB agonist, has been proposed as a viable therapeutic alternative to BDNF in crossing the Blood-Brain Barrier (BBB) and promoting growth, differentiation, maintenance, and survival of neurons. Here, we expand on our previous study investigating the therapeutic role of DHF on the cortical and hippocampal brain regions of the Tg26 mice, an animal model of HAND. We detected increased immunoreactivity for ion channels (SUR1, TRPM4) and the water channel aquaporin-4 (AQP4), suggesting an ionic and osmotic imbalance in the brains of Tg26 mice. Tg26 mice also exhibited loss of synaptic stability (SYN, SYP) and nicotinamide metabolism (NAMPT, SIRT1) that were associated with astrogliosis. Furthermore, Tg26 mice demonstrated increased iNOS and reduced HO-1/NRF2 expressions, implicating increased ER and oxidative stress. DHF treatment in Tg26 mice reversed these pathological changes. These data suggest crosstalk among TrkB, Akt, and related transcription factors (NF-κB, STAT3, and NRF2) as an underlying mechanism of Tg26-associated pathology in the brain. Finally, taken together with our prior study, these results further highlight a therapeutic role of DHF in promoting neuroprotection in HAND that may be applied in conjunction with current antiviral therapies.

Stroke and acute myocardial infarction are primary global causes of mortality. Statistical studies have shown that acute myocardial infarction is responsible for around 9 million deaths each year. Ischemic stroke and myocardial infarction have a significant role in global adult physical disabilities. While reperfusion is vital for tissue recovery, it may paradoxically, inadvertently increase damage through oxidative stress, inflammation, and cell death. Early reperfusion procedures are currently the sole therapy to reduce infarct size. There are many mysteries about heart biology. It is not known the source of energy for myocardial tissues. The heart-beating force (120 mm Hg) cannot explain how erythrocytes are impelled through almost 95,000 km of capillaries in less than 5 minutes. A better knowledge of how the heart is oxygenated should allow the development of new therapies.

Methylenetetrahydrofolate Reductase (MTHFR) is an important enzyme of the folate cycle, which is required to convert 5,10-methyltetrahydrofolate into 5-methyltetrahydrofolate (5-methylTHHF). 5-methyl THF is a methyl group donor for several cellular methylation processes. It also donates methyl group for the conversion of homocysteine into methionine, the higher concentration of which is toxic. MTHFR gene C677T polymorphism is clinically important polymorphism and the variant MTHFR (A222V) enzyme has reduced activity, hence increasing the requirement for folic acid. Less conversion of folate to 5-methyl-THF due to C677T polymorphism results in a higher plasma concentration of homocysteine (hyperhomocysteinemia). Individuals having C677T polymorphism are susceptible to various diseases, including reproductive problems like male infertility, polycystic ovary syndrome, Recurrent Pregnancy Loss (RPL), Preeclampsia (PE), placental abruption, and adverse pregnancy outcomes. MTHFR C677T polymorphism mimics folate deficiency, and folate is required for DNA synthesis, repair, methylation, and proper chromosome segregation, and all these processes are important for foetal growth and normal development. Methylation and demethylation processes control the gene expression of about 45% of human genes. Impaired methylation influences the expression of genes involved in the regulation of hormones, spermatogenesis, and oogenesis. In males, oxidative stress damages sperm DNA decreases sperm motility, and may impair fertilization capability. In pregnant women, hyperhomocysteinemia increases oxidative stress and inflammation within the placenta, which causes damage to placental tissue, impairs its function, and disrupts foetal development. Further, hyperhomocysteinemia (HHcy) is embryotoxic and neurotoxic and is responsible for congenital anomalies in the foetus. This review supports the idea that MTHFR C677T polymorphism is associated with an increased risk for male infertility, PCOS, RPL, PE, and congenital anomalies. This review may provide a clue toward a better understanding of the correlation between the MTHFR C677T polymorphism and its detrimental effects on human reproductive health.

The role of free radicals and antioxidants is often underestimated despite their involvement in key metabolic processes, although they participate in many important metabolic processes in the life of humans, animals and plants. Their quantity and quality differ from each other, which is not respected. Each cell is attacked approximately 10,000 times by free radicals. Oxidative stress is the cause of many problems, especially in viral diseases. Monitoring of redox potentials in body fluids is usually not carried out. Viral replication is influenced by oxidative energy, derived from either host metabolism or free radical activity, which is supplied by oxidation by free radicals or the host. Nucleic acid mutations due to the effect of free radicals can be the cause of carcinomas, and possible defense against mutations could help eradicate dangerous viruses. The importance of malondialdehyde and antibodies against it is discussed. Eliminating free radicals, reducing lipoperoxidation, and protecting against environmental oxidative stress are important factors for human health.Study objective: To highlight the importance of free radicals, antioxidants and redox potentials for patient diagnosis and therapy.Methods: This study synthesizes findings from multiple published sources, including our own research.Results: Findings highlight the role of free radicals in oxidative stress, DNA damage, and viral replication, with redox potential (ORP) and Malondialdehyde (MDA) identified as key diagnostic markers.Conclusion: Monitoring oxidative balance and targeting free radical activity are essential for preventing cellular damage and improving clinical outcomes in oxidative stress-related diseases.

Background: Monotherapy for liver dysfunction in diabetes is less effective. This study investigated the effect of combined linagliptin and metformin therapy on liver function in diabetic rats. Methods and materials: Sixty-four mature male (200-300 g) Wistar rats were used. Streptozotocin (35 mg/kgb.wt) was repeatedly injected intraperitoneally to induce diabetes. The rats were grouped into eight groups (n = 8). Group I: control; Group II: control + 10 mg/kgb.wt linagliptin; Group III: control + 200 mg/kgb.wt metformin; Group IV; control + 10 mg/kgb.wt linagliptin + 200 mg/kgb.wt metformin; Group V: diabetic; Group VI: diabetic + 10 mg/kgb.wt linagliptin; Group VII: diabetic + 200 mg/kgb.wt metformin; Group VIII: diabetic + 10 mg/kgb.wt linagliptin + 200 mg/kgb.wt metformin. The animals were sacrificed on the last day of the experiment, blood and liver samples were collected for biochemical assay. Results: Insulin, blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-cholesterol), liver function biomarkers, liver glucose metabolic enzymes, malondialdehyde and inflammatory markers increased (p < 0.05) significantly. High-density lipoprotein-cholesterol (HDL-cholesterol), liver antioxidant, glycogen, and glycogen synthase were reduced significantly in diabetic rats. Linagliptin and metformin administration single and combined reduced the insulin, blood glucose, glycated hemoglobin, total cholesterol, triglycerides, LDL-cholesterol, liver function biomarkers, liver glucose metabolic enzymes, malondialdehyde, and inflammatory markers, and increased the HDL-cholesterol, liver antioxidant, glycogen and glycogen synthase in diabetic rats.Conclusion: Linagliptin monotherapy alone efficiently controls hyperglycemia and remarkably improves liver functions. Combining linagliptin and metformin could be used as safe and effective therapy for liver dysfunction progression in diabetes.

Cannabis sativum has long been used globally for hallucination. However, detrimental effects on female reproduction have never been studied. The aim of the present paper is to evaluate cannabinoid-induced oxidative stress and reproductive containment in female mice. Fifteen adult female Parkes strain mice were randomly chosen from institutional animal houses (n = 5/group) with ad libitum access to water and food. Animals were grouped into control (vehicle-treated), treated with 6mg of cannabis/100 g of body weight, and 12 mg of cannabis/100 g of body weight. After 15 days all animals were sacrificed and tissues were collected for histology, immunohistochemistry, and estimations of different parameters. Histology and immunohistochemistry (of Cannabinoid Receptor 1; CB1) were performed following standardized protocols. All parameters were estimated either by standard biochemical protocols or by kit following the manufacturer’s protocol. Stress parameters (Super Oxide Dismutase; SOD, Catalase, CAT; Malonaldehyde, MDA and Glutathione Peroxidase; GPx), apoptotic parameters of thecal cells (by Caspase-3 assay), serum level of Estrogen (E2), steroidogenic parameters (3β Hydroxy-steroid dehydrogenase; 3β HSD and 17β Hydroxy-steroid dehydrogenase; 17β HSD) and expression of CB1 were noted in ovary. Data were analyzed by One-way Analysis of Variance (One-way ANOVA) followed by Duncan’s Multiple Range post hoc Test. We found a significant (p < 0.05) decrease in steroidogenic parameters and a significant increase (p < 0.05)in free radical and apoptotic parameters and CB1 receptor expressions upon dose-dependent cannabis treatment. We may conclude that chronic treatment of cannabis causes reproductive containment in females which has never been addressed previously.

Microplastics (MPs) pose a significant risk to human health, particularly through seafood consumption. Once ingested, MPs can spread from the digestive system to other organs via phagocytosis and endocytosis, leading to toxicological effects. Accumulation of MPs in tissues causes swelling, blockages, oxidative stress, and Cytotoxicity. Studies show MPs alter metabolism, disrupt immune function, and contribute to autoimmune diseases. Chronic exposure has been linked to neurotoxicity, vascular inflammation, and increased cancer risk due to DNA damage. MPs can cross biological barriers, including the placenta, affecting fetal development. Additionally, they serve as vectors for pollutants and bacteria, further complicating health risks. MPs in the bloodstream can trigger inflammatory responses, endothelial adhesion, and red blood cell coagulation, leading to cardiovascular complications. In vitro studies indicate MPs impair renal function and cause long-term inflammation in distal tissues. Moreover, oxidative stress caused by MPs plays a critical role in carcinogenicity. Despite growing evidence of adverse health effects, further research is necessary to understand the full impact of MPs’ exposure on human health and develop effective mitigation strategies.