Chronic exposure of adult male Wistar rats to bisphenol A causes testicular oxidative stress: Role of gallic acid.

OBJECTIVES: Bisphenol A (BPA) has been reported that among other male reproductive dys-functions, it can cause marked estrogenic effects including alteration in serum hormones as well as testicular lesions in exposed animals. This work sought to study the role of gallic acid (GA), a known antioxidant, on the BPA-induced testicular oxidative stress in adult male Wistar rats using serum hormone analysis, histopathology, and biochemical assays. METHODS: Adult male rats were divided into four groups (n=10) including control (0.2 ml of corn oil), GA (20 mg/kg/day), BPA (10 mg/kg/day), BPA+GA (BPA, 10 mg/kg/day + GA, 20 mg/kg/day). All medications were given by oral gavage for 45 consecutive days. The body and testicular weights were measured. Blood and organ samples were collected for the serum hormonal assay: testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL), and tissue biochemistry analysis: superoxide dismutase (SOD), reduced glutathione (GSH), glutathione-S-transferase (GST), malondialdehyde (MDA), hydrogen peroxide (H2O2), respectively. RESULTS: The BPA-treated rats showed significant reduction in the gonadosomatic index. BPA also caused significant decrease in the levels of the serum testosterone and prolactin. Furthermore, BPA induced testicular oxidative stress by decreasing the activities of antioxidant enzymes and increasing reactive oxygen species. However, co-treatment with GA protected against these alterations. CONCLUSION: Findings from the present study confirmed the previously reported data and show that the ability of GA, as a potent antioxidant, may protect against BPA-induced alterations in the male reproductive function. Hence, GA protects against testicular oxidative stress in adult male Wistar rats following chronic exposure to BPA.

Maternal exposure to environmentally relevant doses of bisphenol A causes reproductive dysfunction in F1 adult male rats: protective role of melatonin.

This study investigated the protective effects of melatonin (MLT), a potent antioxidant, in male Wistar rats exposed to environmentally relevant doses of bisphenol A (BPA) in utero. Pregnant Wistar rats were randomly assigned into five groups. Group 1 (control) received 0.2 mL 1% dimethyl sulfoxide (DMSO)/99% canola oil as vehicle; group 2 received BPA at 25 µg/kg/day; group 3 received BPA at 250 µg/kg/day; group 4 received BPA at 25 µg/kg/day with concurrent MLT 1 mg/kg/day while group 5 received BPA at 250 µg/kg/day with concurrent MLT 1 mg/kg/day. Treatments were by gavage from gestational day (GD) 10-21. The BPA-treated rats showed dose-dependent significant reduction in body weight, gonosomatic index, sperm motility, livability and count. Also, BPA caused significant reduction in the levels of serum testosterone and luteinizing hormone while it caused significant increases in the levels of follicle stimulating hormone as well as estradiol. Furthermore, BPA induced testicular oxidative stress including significant decreases in the activities of testicular SOD, GSH and GPx as well as GST, increasing the levels of testicular MDA and H2O2. It further induced interstitial necrosis and germinal cell degeneration in the testis with a subsequent diminution of the tubular and luminal diameter. However, co-treatment with MLT offered protection against testicular damage induced by BPA. Melatonin is likely to protect against alterations of the male reproductive system caused by BPA through a direct action on the mechanism of anti-oxidants as well as through the inhibition of necrosis.

Melatonin attenuates bisphenol A-induced toxicity of the adrenal gland of Wistar rats.

This study investigated the role of melatonin (MLT) on adrenal gland toxicity induced by bisphenol A (BPA). Adult male rats were divided into four groups of seven animals each: Group I (control) received oral 0.2 ml canola oil; group II received intra-peritoneal 10 mg/kg BW/day MLT; and group III received oral BPA (10 mg/kg BW/day). Group IV rats were treated with same dose of BPA as group III with a concomitant intra-peritoneal 10 mg/kg BW/day MLT. All treatments lasted for 14 days. BPA significantly increased (P < 0.05) adrenal index, circulating levels of corticosterone and adrenocorticotropic hormone (ACTH) in the rats. BPA caused marked vascular congestion, hyperplasia, cellular distortion, increased lipid peroxidation, decreased antioxidant enzymes, and decreased expression of αSmooth muscle actin as well as vimentin proteins. The concomitant treatment with MLT ameliorated these BPA-induced alterations. It is likely that melatonin attenuates BPA-induced alterations of the adrenal gland of rats through the antioxidant defense mechanism.

Melatonin ameliorates bisphenol A-induced perturbations of the prostate gland of adult Wistar rats.

Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that has been demonstrated to induce alterations in reproductive organs while melatonin (ML), an antioxidant, present in plants and animals, is capable of protecting against EDC-induced alterations. Adult male Wistar rats (average weight, 240 + 10 g) were divided into four groups of ten animals each: Rats in group I (control) received oral 0.2 ml 1% dimethyl sulfoxide (DMSO)/99% canola oil as vehicle; group II received intra-peritoneal 10 mg/kg BW/day ML. Group III received oral BPA dissolved in DMSO and solubilized in canola oil at 10 mg/kg BW/day. Group IV were treated with same dose of BPA as group III with a concomitant intra-peritoneal 10 mg/kg BW/day ML. All treatments lasted for 14 days. BPA significantly increased the prostatic index of the rats while ML ameliorated it. BPA significantly increased serum levels of estrogen as well as prostate-specific antigen but decreased serum testosterone in the rats while concomitant treatment with ML ameliorated these alterations. Also, BPA caused vascular congestion, hyperplasia (functional, reactive and atypical) of prostatic epithelium as well as tubular atrophy the rats while ML attenuated the observed lesions. Decreased localization of αSmooth muscle actin, vimentin and S100 proteins were observed in the BPA-treated rats while these decreases were ameliorated by ML. The present study has shown that sub-acute oral administration of BPA induced alterations in prostatic index, serum hormone levels, down-regulated protein localization and induced morphological lesions of the prostate gland in rats while concomitant treatment with intra-peritoneal ML ameliorated these conditions. Hence, low dose of ML can protect against BPA-induced toxicity of the prostate gland of rats.