Preliminary Investigation on the Ameliorative Role Exerted by D-Aspartic Acid in Counteracting Ethane Dimethane Sulfonate (EDS) Toxicity in the Rat Testis

Abstract

Herein is reported the first evidence of the protective role of D-aspartic acid (D-Asp) in preventing the toxic effect exerted by the alkylating agent ethane dimethane sulfonate (EDS) in the rat testis. We confirmed that EDS treatment specifically destroyed Leydig cells (LC), resulting in the drastic decrease of the serum testosterone level and producing morphological changes in the germinal tubules, i.e., altered organization of the epithelium, loss of cell contacts and the consequent presence of empty spaces between them, and a reduce number of spermatozoa. Moreover, an increase of TUNEL-positive germ cells, other than alteration in the protein level and localization of two LC “markers”, StAR and PREP, were observed. Interestingly, results obtained from rats pre-treated with D-Asp for 15 days before EDS-injection showed that all the considered parameters were quite normal. To explore the probable mechanism(s) involved in the protection exerted by D-Asp, we considered the increased oxidative stress induced by EDS and the D-Asp antioxidant effects. Thiobarbiturc acid-reactive species (TBARS) levels increased following EDS-injection, while no change was observed in the D-Asp + EDS treated rats. Our results showed that D-Asp may be used as a strategy to mitigate the toxic effects exerted by environmental pollutants, as endocrine disrupters, in order to preserve the reproductive function.

Preliminary study of the ameliorative effects of melatonin on cadmium‐induced morphological and biochemical alterations in the rat Harderian gland

“…On the contrary, several experimental data proved that testosterone negatively correlated with MCN (Dias et al, 2022). For instance, the use of ethane dimethane sulphonate, an alkylating agent that selectively disrupts Leydig cells (Venditti et al, 2021c), increased MCN in testis (Di Matteo et al, 1992; Minucci et al, 1992) and in the HG (Di Matteo et al, 2000). Here, using the toluidine blue staining (Figure 3a,b), we observed a significant increase in the MCN in the HG treated with Cd ( p < 0.01) as compared with those of control group.…”

Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis

“…Indeed, it accumulates in neuroendocrine tissues and interferes with the HPT axis [ 56 , 57 ]; thus, the altered protein levels of StAR and 3β-HSD, key enzymes involved in testosterone (T) biosynthesis, may consequently have an impaired steroid availability and production at the central and local level, resulting in the reduction in serum and testicular T concentrations [ 7 ]. It must be pointed out that T regulates the whole spermatogenetic process, acting as a “survival factor” to protect GC from apoptosis, and its depletion may be an additional cause of the augmented apoptosis, together with the alteration of the histological structure [ 58 ]. Data confirmed that MLT effectively reduced oxidative stress and Cd-induced apoptosis, underlined by the reduced TBARS concentration and the increased CAT and SOD antioxidant activity as well as the reduced number of TUNEL-positive cells and BAX protein levels, respectively.…”

Oral D-Aspartate Treatment Improves Sperm Fertility in Both Young and Adult B6N Mice

“…Notably, it stimulates tyrosine phosphorylation, facilitates cholesterol efflux, and enhances cAMP generation, all of which are necessary cellular processes implicated in the regulation of sperm capacitation and acrosome reaction [ 58 ]. On the other hand, there are also some reports on the antioxidant effect of D-Asp [ 59 , 60 ]. It would be of interest to investigate the pro-oxidant environment generated by the D-Asp treatment and its potential influence on sperm quality and fertility in future studies.…”