Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary Study.

A particular attribute of the brain lies in the ability to learn, acquire information from the environment, and utilize the learned information. Previous research has noted that various factors (e.g., age, stress, anxiety, pathological issues), including antipsychotic medications, affect the brain and memory. The current study aimed to reveal the effects of chronic metformin treatment on the cognitive performance of rats and on commonly measured markers for oxidative stress. Wistar male rats (n = 40) were randomly divided into four groups: CTR (n = 10)-control group, METF (n = 10)-animals receiving metformin 500 mg/kg, HAL (n = 10)-animals receiving haloperidol 2 mg/kg, and HALMETF (n = 10)-animals receiving haloperidol 2 mg/kg and metformin 500 mg/kg. The medication was administered daily by oral gavage for 40 days. Memory and learning were assessed using the Morris Water Maze (MWM) test. At the end of the MWM, the rodents were decapitated under anesthesia, and the brain and blood samples were assayed by liquid chromatography for markers of oxidative stress (malondialdehyde, MDA, reduced/oxidized glutathione ratio, GSH/GSSG). The quantification of brain-derived neurotrophic factor (BDNF) was performed using the conventional sandwich ELISA technique. In the HALMETF group, metformin attenuated the negative effects of haloperidol. Brain and plasma MDA levels increased in the HAL group. Brain and plasma GSH/GSSG ratios and BDNF levels did not reveal any differences between groups. In conclusion, metformin treatment limits the deleterious cognitive effects of haloperidol. The effect on oxidative stress markers may also point toward an antioxidant-like effect of metformin, but this needs further tests for confirmation.

Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review.

Trimetazidine (TMZ), used for treating stable angina pectoris, has garnered attention in the realm of sports due to its potential performance-enhancing properties, and the World Anti-Doping Agency (WADA) has classified TMZ on the S4 list of prohibited substances since 2014. The purpose of this narrative mini-review is to emphasize the biochemical aspects underlying the abusive use of TMZ among athletes as a metabolic modulator of cardiac energy metabolism. The myocardium's ability to adapt its energy substrate utilization between glucose and fatty acids is crucial for maintaining cardiac function under various conditions, such as rest, moderate exercise, and intense effort. TMZ acts as a partial inhibitor of fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase (KAT), shifting energy production from long-chain fatty acids to glucose, reducing oxygen consumption, improving cardiac function, and enhancing exercise capacity. Furthermore, TMZ modulates pyruvate dehydrogenase (PDH) activity, promoting glucose oxidation while lowering lactate production, and ultimately stabilizing myocardial function. TMZs role in reducing oxidative stress is notable, as it activates antioxidant enzymes like glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). In conclusion, TMZs biochemical mechanisms make it an attractive but controversial option for athletes seeking a competitive edge.

The Lack of Standardization and Pharmacological Effect Limits the Potential Clinical Usefulness of Phytosterols in Benign Prostatic Hyperplasia.

The prevalence of benign prostatic hyperplasia (BPH) markedly increases with age. Phytotherapeutic approaches have been developed over time owing to the adverse side effects of conventional medications such as 5-reductase inhibitors and α1-adrenergic receptor antagonists. Therefore, dietary supplements (DS) containing active compounds that benefit BPH are widely available. Phytosterols (PSs) are well recognized for their role in maintaining blood cholesterol levels; however, their potential in BPH treatment remains unexplored. This review aims to provide a general overview of the available data regarding the clinical evidence and a good understanding of the detailed pharmacological roles of PSs-induced activities at a molecular level in BPH. Furthermore, we will explore the authenticity of PSs content in DS used by patients with BPH compared to the current legislation and appropriate analytical methods for tracking DS containing PSs. The results showed that PSs might be a useful pharmacological treatment option for men with mild to moderate BPH, but the lack of standardized extracts linked with the regulation of DS containing PSs and experimental evidence to elucidate the mechanisms of action limit the use of PSs in BPH. Moreover, the results suggest multiple research directions in this field.