The effect of coadministration of α-tocopherol and ascorbic acid on arsenic trioxide-induced testicular toxicity in adult rats.
BACKGROUND
Arsenic, acting as an endocrine disruptor, causes reproductive malfunctions. Studies have been undertaken to find out whether the co-supplementation of α-tocopherol and ascorbic acid (AT-AA) could reduce the arsenic-induced testicular toxicity caused by oxidative stress and resulting DNA damage.


METHODS
Adult male Wistar rats (120±10 g) were given arsenic trioxide [3 mg/kg body weight (b.wt.) per day] for 30 consecutive days and the supplement group received α-tocopherol (400 mg/kg b.wt. per day) and ascorbic acid (200 mg/kg b.wt. per day). Reproductive functions were evaluated with respect to the histoarchitecture, gametokinetic activity, androgenic potential, glutathione-dependent antioxidant status and DNA damage of the testis.


RESULTS
Arsenic treatment caused marked reduction in the relative weight of the testis (p<0.05) but showed no effect on body weight. The number of germ cells at stage VII of the spermatogenic cycle (p<0.01), the seminiferous tubular diameter (p<0.001) and Leydig cell nuclear area (p<0.01) were significantly reduced. Notable decrease in the activities of testicular Δ5, 3β-HSD (p<0.05) and 17β-HSD (p<0.01) with a concomitant fall in serum testosterone level (p<0.01) along with significant diminution in testicular glutathione S-transferase (p<0.05) activity and reduced glutathione level (p<0.01) were observed. Significant DNA damage (p<0.001) in spermatogenic cells was also noted. All these alterations including DNA strand breakage were seen to be protected with the coadministration of AT-AA.


CONCLUSIONS
The data suggest that the protection of testicular toxicity in arsenic-exposed adult rats is possible with combined coadministration of AT-AA.
Prabir Kumar
PK
Mukhopadhyay
Avijit
A
Dey
Sanjit
S
Mukherjee
Nirmal Kumar
NK
Pradhan
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004249:DNA Damage; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D052244:Endocrine Disruptors / Q000633:toxicity*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000097:blood; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D001152:Arsenicals; D052244:Endocrine Disruptors; D010087:Oxides; D013739:Testosterone; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D000077237:Arsenic Trioxide