Attenuation of sodium arsenite mediated ovarian DNA damage, follicular atresia, and oxidative injury by combined application of vitamin E and C in post pubertal Wistar rats.

Arsenic being a toxic metalloid ubiquitously persists in environment and causes several health complications including female reproductive anomalies. Epidemiological studies documented birth anomalies due to arsenic exposure. Augmented reactive oxygen species (ROS) generation and quenched antioxidant pool are foremost consequences of arsenic threat. On the contrary, Vitamin E (VE) and C (VC) are persuasive antioxidants and conventionally used in toxicity management. Present study was designed to explore the extent of efficacy of combined VE and VC (VEC) against Sodium arsenite (NaAsO2) mediated ovarian damage. Thirty-six female Wistar rats were randomly divided into three groups (Grs) and treated for consecutive 30 days; Gr I (control) was vehicle fed, Gr II (treated) was gavaged with NaAsO2 (3 mg/kg/day), Gr III (supplement) was provided with VE (400 mg/kg/day) & VC (200 mg/kg/day) along with NaAsO2. Marked histological alterations were evidenced by disorganization in oocyte, granulosa cells and zona pellucida layers in treated group. Considerable reduction of different growing follicles along with increased atretic follicles was noted in treated group. Altered activities ofΔ5 3ß-Hydroxysteroid dehydrogenase and 17ß-Hydroxysteroid dehydrogenase accompanied by reduced luteinizing hormone, follicle-stimulating hormone and estradiol levels were observed in treated animals. Irregular estrous cyclicity pattern was also observed due to NaAsO2 threat. Surplus ROS production affected ovarian antioxidant strata as evidenced by altered oxidative stress markers. Provoked oxidative strain further affects DNA status of ovary. However, supplementation with VEC caused notable restoration from such disparaging effects of NaAsO2 toxicities. Antioxidant and antiapoptotic attributes of those vitamins might be liable for such restoration.

Vitamin C and E supplementation can ameliorate NaF mediated testicular and spermatozoal DNA damages in adult Wistar rats.

OBJECTIVE: Present study was designed to explore the efficacy of vitamin C and E (VC&VE) against fluoride mediated testicular, epididymal and spermatozoal anomalies. MATERIALS AND METHODS: Thirty two adult Wistar rats were divided into four groups. Group-I was control; Group-II received sodium fluoride (NaF) at 15 mg/kg/day dose; Group-III was provided with VC (200 mg/kg/day) and VE (400 mg/kg/day) plus NaF; Group-IV received only VC&VE. Structural integrity and oxidative stress markers (superoxide dismutase, catalase, malondialdehyde and protein carbonyl) of testis and epididymis were assessed. Spermatozoal parameters (count, motility, viability and hypo-osmotic swelling) were evaluated. Testicular functional maker enzymes (acid phosphatase, alkaline phosphatase and lactate dehydrogenase) were also assessed. Integrity of testicular and spermatozoal DNA was evaluated. Testicular fluoride content was measured. RESULT: Fluoride induced structural changes and alterations of oxidative stress markers were observed in testis and epididymis. Spermatozoal potentials were altered and reduced activities of testicular functional marker enzymes were observed. Fluoride caused testicular and spermatozoal DNA damages. VC&VE supplementation resulted in protection from all fluoride mediated alterations and helped in attenuating testicular fluoride accumulation. CONCLUSION: Antioxidant properties of VC&VE ameliorated fluoride mediated reproductive damages but only supplementation did not exhibit any notable effect compared to control rats.

High-Protein Diet Ameliorates Arsenic-Induced Oxidative Stress and Antagonizes Uterine Apoptosis in Rats.

Arsenic toxicity purportedly threats a broad spectrum of female reproductive functions. We investigated the remedial role of a casein- and pea protein-enriched high-protein diet (HPD) in combating the arsenic insult. Cyclic female rats maintained on standard diet (n = 6) or an isocaloric HPD (n = 6) were gavaged with As2O3 at 3 mg/kg BW/rat/day (n = 12) for 28 days. Vehicle-fed rats (n = 6) maintained on the standard diet served as the control. We monitored the estrus cycles and performed the histomorphometric analyses of the uterus and ovary. Uterine luminal epithelial (ULE) ultrastructure was appraised by scanning electron microscopy. Uterine oxidative stress was evaluated in the forms of ROS generation and activities of the ROS scavengers. The uterine apoptotic manifestation was blueprinted by Western blot analysis of caspase-3 and Bax expression. Arsenic treatment arrested the follicular maturation and disrupted the estrus cycles with a typical increase in the diestrus index. Shrunken endometrial glands and thinned microvilli density of the ULE reflected loss of cell polarity and mislaid uterine homeostasis. Increased ROS generation and attenuated activities of the ROS scavengers marked a state of uterine oxidative imbalance and loss of redox regulation. Superfluous expression of procaspase-3, cleaved caspase-3, and Bax mirrored an inflated state of uterine apoptosis. HPD supplementation, by and large, counteracted these arsenic impacts and maintained the frameworks close to the control levels. In conclusion, arsenic mediates its reproductive toxicity, at least in part, by upsetting the uterine ROS homeostasis and redox regulation. Pea proteins and casein-supplemented HPD can counteract the arsenic effects and maintain the reproductive functions.

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, 3ß-HSD (p<0.05) and 17ß-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.