Sodium acetate abates lead-induced sexual dysfunction by upregulating testosterone-dependent eNOS/NO/cGMP signaling and activating Nrf2/HO-1 in male Wistar rat.

Oxidative stress has been linked with lead toxicity, including lead-induced sexual dysfunction. On the contrary, sodium acetate has been proven to exert antioxidant activity. However, the effect of sodium acetate on lead-induced sexual dysfunction has not been fully explored. This study investigated the effect of sodium acetate on lead-induced sexual dysfunction, exploring the involvement of testosterone, eNOS/NO/cGMP, and Nrf2/HO-1 signaling. Twenty male Wistar rats with similar weights were randomly assigned into four groups (n = 5 rats/group) after two weeks of acclimatization. Animals were vehicle-treated (0.5 ml/day of distilled water, per os), acetate-treated (200 mg/kg/day, per os), lead-treated (20 mg/kg/day, per os), or lead + acetate-treated. The results revealed that sodium acetate treatment attenuated lead-induced rise in penile lead, malondialdehyde and oxidized glutathione concentrations, and acetylcholinesterase activity. In addition, lead exposure prolonged mount, intromission, and ejaculation latency and reduced mount, intromission, and ejaculation frequency, as well as the motivation to mate and penile reflex, which were improved by acetate treatment. More so, acetate treatment ameliorated lead-induced reductions in absolute and relative penile weight, eNOS, NO, cGMP, luteinizing hormone, follicle-stimulating hormone, testosterone, dopamine, Nrf2, HO-1, and reduced glutathione concentrations, as well as glutathione reductase, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, and catalase activities. In conclusion, this study demonstrates that sodium acetate attenuated lead-induced sexual dysfunction by upregulating testosterone-dependent eNOS/NO/cGMP and Nrf2/HO-1 signaling. Despite the compelling data presented in this study, other possible associated mechanisms in the protective role of acetate should be explored.

Acetate Abates Arsenic-Induced Male Reproductive Toxicity by Suppressing HDAC and Uric Acid-Driven Oxido-inflammatory NFkB/iNOS/NO Response in Rats.

Arsenic is associated with male reproductive toxicity through histone deacetylation and oxido-inflammatory injury. Notwithstanding, short-chain fatty acids such as acetate exert anti-oxido-inflammatory activities and inhibit histone deacetylation. This study investigated the impact of acetate on arsenic-induced male reproductive toxicity. Forty eight adult male Wistar rats were allotted into any of these four groups (n = 12 rats per group): vehicle-treated, sodium acetate-treated, arsenic-exposed, and arsenic-exposed + sodium acetate-treated. The results revealed that arsenic exposure prolonged the latencies of mount, intromission, and ejaculation and reduced the frequencies of mount, intromission, and ejaculation, as well as mating and fertility indices, litter size and weight, anogenital distance, anogenital index, and survival rate in male F1 offspring at weaning. Also, arsenic reduced the circulating levels of gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone, and testosterone and testicular 3ß-hydroxysteroid dehydrogenase and 17ß-hydroxysteroid dehydrogenase activities. In addition, arsenic reduced the daily and total spermatid production, sperm count, motility, and viability but increased the percentage of sperm cells with abnormal morphology. Furthermore, arsenic increased testicular xanthine oxidase activity, uric acid, and malondialdehyde levels, and reduced glutathione content, superoxide dismutase and catalase activities, total antioxidant capacity, and Nrf2 level. More so, arsenic exposure increased testicular iNOS activity and nitric oxide (NO), TNF-α, IL-1ß, IL-6, and NFkB levels as well as Bax, caspase 9, and caspase 3 activities, and reduced Bcl-2. These findings were associated with arsenic-induced increase in testicular arsenic concentration, histone deacetylase activity, and reduced testicular weight. Histopathological examination revealed that arsenic also disrupted testicular histoarchitecture, which was accompanied by altered testicular planimetry and reduced spermatogenic cells. Notwithstanding, sodium acetate alleviated arsenic-induced sexual dysfunction as well as biochemical and histological alterations. These were accompanied acetate-driven downregulation of histone deacetylase (HDAC) activity. Succinctly, acetate attenuated arsenic-induced male reproductive toxicity by suppressing HDAC and uric acid-driven oxido-inflammatory NFkB/iNOS/NO response.