Arsenic-induced toxicity and the protective role of ascorbic acid in mouse testis.
Oxidative stress has been suggested to be a major cause of male reproductive failure. Here, we investigated whether arsenic, which impairs male reproductive functions in rodent models, acts by inducing oxidative stress. Male 8-week-old ICR mice were given drinking water containing 20 or 40 mg/l sodium arsenite with or without 0.75 or 1.5 g/l of the antioxidant ascorbic acid for 5 weeks. The arsenic-treated mice showed decreased epididymidal sperm counts and testicular weights compared to untreated mice. These effects were reversed in mice that were co-treated with ascorbic acid. Similarly, arsenic treatment lowered the activities of testicular 3beta-hydroxysteroid dehydrogenase (HSD) and 17beta-HSD, which play important roles in steroidogenesis, and this was reversed by co-treatment with ascorbic acid. The testicles of arsenic-treated mice had decreased glutathione (GSH) levels (which correlate inversely with the degree of cellular oxidative stress) and elevated levels of protein carbonyl (a marker of oxidative damage to tissue proteins). Ascorbic acid co-treatment reversed both of these effects. Thus, ascorbic acid blocks both the adverse effects of arsenic on male reproductive functions and the arsenic-induced testicular oxidative changes. These observations support the notion that arsenic impairs male reproductive function by inducing oxidative stress.
Chang
Soo Im
SI
College of Veterinary Medicine, BK21 Program for Veterinary Science, Seoul National University, Seoul, 151-742, Republic of Korea.
Jin
Bohwan
B
Youn
Pilju
P
Park
Changbo
C
Park
Jung-Duck
JD
Ryu
Doug-Young
DY
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001151:Arsenic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D001205:Ascorbic Acid / Q000494:pharmacology*; D015415:Biomarkers; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D012098:Reproduction / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013733:Testicular Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D013737:Testis / Q000201:enzymology / Q000473:pathology; D013739:Testosterone / Q000097:blood
D000975:Antioxidants; D015415:Biomarkers; D013739:Testosterone; D008315:Malondialdehyde; D005978:Glutathione; D001151:Arsenic; D001205:Ascorbic Acid