Abstract
Since its discovery in 1905 and its employment in everyday medical practice as a local anesthetic, to its highly controversial endorsement as an “anti-aging” molecule in the sixties and seventies, procaine is part of the history of medicine and gerontoprophylaxis. Procaine can be considered a “veteran” drug due to its long-time use in clinical practice, but is also a molecule which continues to incite interest, revealing new biological and pharmacological effects within novel experimental approaches. Therefore, this review is aimed at exploring and systematizing recent data on the biochemical, cellular, and molecular mechanisms involved in the antioxidant and potential geroprotective effects of procaine, focusing on the following aspects: (1) the research state-of-the-art, through an objective examination of scientific literature within the last 30 years, describing the positive, as well as the negative reports; (2) the experimental data supporting the beneficial effects of procaine in preventing or alleviating age-related pathology; and (3) the multifactorial pathways procaine impacts oxidative stress, inflammation, atherogenesis, cerebral age-related pathology, DNA damage, and methylation. According to reviewed data, procaine displayed antioxidant and cytoprotective actions in experimental models of myocardial ischemia/reperfusion injury, lipoprotein oxidation, endothelial-dependent vasorelaxation, inflammation, sepsis, intoxication, ionizing irradiation, cancer, and neurodegeneration. This analysis painted a complex pharmacological profile of procaine: a molecule that has not yet fully expressed its therapeutic potential in the treatment and prevention of aging-associated diseases. The numerous recent reports found demonstrate the rising interest in researching the multiple actions of procaine regulating key processes involved in cellular senescence. Its beneficial effects on cell/tissue functions and metabolism could designate procaine as a valuable candidate for the well-established Geroprotectors database.
Highlights
Procaine was synthesized by Alfred Einhorn in 1905 and introduced in clinical practice as Novocain, soon becoming a local anesthetic prototype
As early as 1892, the German chemist Alfred Einhorn began to model on the structural formula of cocaine, an alkaloid extracted from the leaves of Erythroxylum coca and the first known local anesthetic, in order to obtain less addictive molecules, but with similar or enhanced anesthetic qualities
There are reports of studies which comparatively examined the effects of procaine and other anesthetics in different age-related maladies reported a lack of efficacy, as well the presence of toxicity or even severe side-effects [13, 14, 120–123]
Summary
Procaine was synthesized by Alfred Einhorn in 1905 and introduced in clinical practice as Novocain, soon becoming a local anesthetic prototype. Recent progresses in the field of aging research led to the development of a new class of drugs—geroprotectors, with the ability to target fundamental mechanisms of aging common to multiple age-related diseases, such as response to oxidative damage, inflammation, hypermethylation, cellular senescence, and autophagy [18]. The aim of this review is to explore and systematize data on biochemical, cellular, and molecular mechanisms involved in the antioxidant and alleged geroprotective actions of procaine and GH3, focusing on the following aspects: (1) the research state-of-the-art, through an objective examination of scientific literature for the last 30 years—describing both positive and negative research outcomes; (2) the experimental data supporting the beneficial effects of procaine in preventing the agerelated pathology; and (3) the multitude of ways procaine impacts oxidative stress, atherogenesis, cerebral age-related pathology, and DNA methylation
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