Paternal exposure to arsenic resulted in oxidative stress, autophagy, and mitochondrial impairments in the HPG axis of pubertal male offspring.

Despite the knowledge of AS-induced reprotoxicity, the literature concerning arsenic trioxide (As2O3)-induced oxidative stress and consequent intracellular events, like autophagy process, in the hypothalamic-pituitary- gonadal (HPG) axis of F1- pubertal male mice is sparse to date. Hence, we made an attempt to study the reproductive toxicities and the underlying mechanisms induced by As2O3 in the HPG axis of pubertal F1- male mice in correlation with oxidative stress-induced autophagy. Parental mice were challenged with As2O3 (0, 0.2, 2, and 20 ppm) from five weeks before mating, and continued till puberty age for the male pups. It was recorded that higher As2O3 doses (2 and 20 ppm) were a potent inducer of oxidative stress and autophagy in the HPG axis. Concomitant with a decrease on mean body weight, total antioxidant capacity, and stereology indices, an increase in the number of MDC-labeled autophagic vacuoles, and MDA/GSH ratio in HPG axis of pubertal F1- male mice which were exposed to higher As2O3 doses was observed. Meanwhile, concomitant with a dose-dependent increment in the gene expression of ATG3, ATG5, Beclin, as well as protein expression of P62, ATG12, and Beclin in HPG axis tissues; a dose-dependent decrease in PI3K and mTOR gene expression was recorded in the HPG tissues of pubertal F1-males. Altogether, our observations suggest that higher doses of As2O3 have detrimental effects on the functionality of HPG axis in pubertal male mice offspring by increasing MDA/GSH ratio and autophagic cell death-related genes and proteins, as well as by reducing total antioxidant capacity.

Is immunosuppression, induced by neonatal thymectomy, compatible with poor reproductive performance in adult male rats?

With increasing knowledge that the immune system has a major impact on reproductive health, the potential for cells arising in organs such as the thymus to alleviate oxidative stress has been revealed. This study addresses the impact of neonatal thymectomy on male reproductive function in pubertal and adult animals. Neonatal Sprague Dawley rats were allotted to four treatments consisting of fully thymectomized, partially thymectomized, intact, and sham-operated rats. Half of the rats in each treatment were sacrificed at 40 and the other half at 80 days of age. Testicular volume, ventral prostate and spleen weight, several sperm attributes (concentration, motility, livability, membrane integrity, sperm penetration into mucus, total antioxidant capacity, mitochondrial dehydrogenase activity), plasma superoxide dismutase, glutathione, and testosterone level as well as fertility decreased in thymectomized rats. Adrenal gland weight, sperm malondialdehyde level, indices of oxidative stress, sperm abnormality, testicular and sperm lipid peroxidation, protein carbonylation, and sperm reactive oxygen species generation increased in thymectomized rats. In thymectomized rats, the testes contained high levels of malondialdehyde but low levels of glutathione and ferric-reducing antioxidant power. Epididymal sperm reactive oxygen species, blood lipid peroxidation, and oxidative stress indices in blood and spermatozoa were highest in fully thymectomized, intermediate in partially thymectomized, and lowest in both pubertal and mature control rats. Blood levels of superoxide dismutase, lipid peroxidation indices, and testosterone, and mitochondrial adenosine triphosphate and dehydrogenase activities in epididymal spermatozoa were lowest in fully thymectomized, intermediate in partially thymectomized, and highest in both pubertal and mature control rats. The data indicated that increased oxidative stress and mitochondrial dysfunction might play a role in the mechanism of immunosuppression-induced testicular and sperm abnormalities.

Comparative in vitro activity of BAY 12-8039 and five other antimicrobial agents against anaerobic bacteria.

The in vitro activity of BAY 12-8039 against 360 anaerobic clinical isolates was determined by the agar dilution method and compared to that of five other antimicrobial agents. BAY 12-8039 and imipenem were the most active agents tested. The following MIC90 values were determined for BAY 12-8039: Peptostreptococcus spp. (50 isolates), 1 mg/l; Propionibacterium acnes (30 isolates). 0.25 mg/l; Clostridium perfringens (30 isolates), 0.5 mg/l; Clostridium difficile (50 isolates), 2 mg/l; Bacteroides fragilis (50 isolates), 1 mg/l; non-fragilis Bacteroides, Porphyromonas, and Prevotella spp. (100 isolates), 2 mg/l; and Fusobacterium spp. (50 isolates), 0.25 mg/l. The results of the present study show that BAY 12-8039 may be useful in the treatment and prophylaxis of anaerobic infections.