Basic & Clinical Pharmacology & Toxicology最新文献

By 2050, roughly 60% of the population will have cardiovascular disease. While a substantial amount of data has been generated over the last few decades that has aided in our understanding of cardiovascular disease pathology, less is known about how to increase resiliency to cardiovascular risk factors that individuals are exposed to on a daily basis. The vascular endothelium is considered the first line of defence against circulating noxious stimuli and, when dysfunctional, is an early risk factor for the development of cardiovascular disease. A vast amount of data has been generated demonstrating how external stress impairs the vascular endothelium; however, there is a paucity of knowledge regarding how to amplify protective pathways and ward off stress and the development of disease, which is the focus of this review. Targeting known protective endothelial pathways may be feasible to increase resiliency to vascular stress. Leveraging stress to boost defence mechanisms within the vascular endothelium is also proposed and may help identify novel therapeutic targets to protect individuals from the stress of everyday life.

In the search for novel treatment strategies for alcohol use disorder (AUD), glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) approved for treating Type 2 diabetes and obesity have caught much attention. GLP-1 is a naturally occurring peptide produced in the small intestines and the brain, regulating plasma glucose levels and satiety. This focused review will report on the preclinical studies, case stories, register-based cohort studies, brain-imaging data and secondary analysis of clinical data supporting the role of GLP-1RAs as a novel treatment of AUD. Several clinical trials are ongoing, examining the potential effects of the GLP-1RA semaglutide in AUD.

Fluvoxamine (FLV), a selective serotonin reuptake inhibitor, is commonly used to treat anxiety, major depressive disorder and obsessive-compulsive disorder, among other psychiatric conditions. This study aims to evaluate the effectiveness of FLV in mitigating damage caused by lipopolysaccharide (LPS) to the female genital tract. Thirty-two female Wistar Albino rats were randomly divided into four groups: control, LPS, LPS-FLV and FLV. At the end of the experimental period, tissues from the ovaries, fallopian tubes and uterus were collected for histological, immunohistochemical and genetic analyses. Histological examination of the LPS group revealed mild to moderate bleeding, oedema and neutrophil infiltration. Additionally, there were signs of endometrial damage in the uterus and loss of cilia in the fallopian tubes. Immunohistochemical analysis showed that LPS increased the expressions of nuclear factor kappa beta (NF-κB) and cation-dependent mannose 6-phosphate receptors (CD-MPR) and reduced kisspeptin-1 (KISS-1) expression. Genetic analysis indicated that LPS increased the expression of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) and aquaporin4 (AQP4) genes while decreasing Claudin-1 expression. However, all these adverse effects were reversed by FLV treatment. The study's findings suggest that FLV may be beneficial in treating LPS-induced damage to the female reproductive system.

The pineal gland secretes melatonin, which regulates various physiological processes; damage to this gland disrupts these functions. This study aimed to investigate the effect of nonylphenol on the pineal gland and the pituitary–adrenal axis, which is associated with this system. The study was initiated using Wistar albino male rats on their postnatal 21st day, a critical developmental stage for endocrine regulation. Nonylphenol was administered via oral gavage at doses of 5, 25 and 125 mg/kg/day, while bisphenol-A was given at 50 mg/kg/day as a positive control. At the end of the treatment period, liver, kidney, pituitary, pineal and adrenal tissues were examined histopathologically. Hormone levels were analysed in serum samples. Significant changes in adrenocorticotropic hormone, melatonin and aldosterone levels were detected in hormone analyses. In contrast, no differences in corticosterone and glucose levels were detected. Histopathological findings showed structural changes in tissues. The effects of nonylphenol on the pituitary–adrenal axis and melatonin vary depending on the experimental protocols employed. However, it is clear that nonylphenol and bisphenol A have negative effects on the pituitary–adrenal axis, pineal gland, liver and kidney. In conclusion, future research should focus on elucidating the molecular mechanisms underlying these effects and developing environmentally friendly strategies to eliminate nonylphenol and bisphenol-A contamination.

Current chelation treatments used for cadmium poisoning may cause some serious side effects. Thus, safer novel treatments could be promising for clinical use. This study evaluated the effects of cannabidiol on Cd toxicity. Four groups of 10 mice were formed: Groups I and III were cadmium-free, while groups II and IV received 50 mg/L cadmium in drinking water. Groups III and IV received daily cannabidiol (25 mg/kg) via intragastric gavage. After 30 days, the animals were killed, and blood and tissue samples were collected. Oxidative stress and inflammation markers, including glutathione, catalase, myeloperoxidase, TNF-α, IL-1β and IL-6, were analysed using ELISA. Additionally, histological evaluations of the liver, kidney and testis were performed. Cadmium exposure reduced glutathione and catalase levels in the blood, liver, kidney and testis, while increasing myeloperoxidase. Cannabidiol mitigated these effects on oxidative stress markers. Cannabidiol also reduced the increase in proinflammatory cytokines. Histopathological analysis revealed reduced liver and kidney damage in cannabidiol-treated groups compared to cadmium-only groups. In addition, histopathological evaluation showed CBD had no protective effect on the testicular tissue against Cd toxicity. Our results indicate that cannabidiol protects against some toxic effects of cadmium. If confirmed by future studies, cannabidiol may be proposed as a novel treatment for cadmium toxicity.