Biological Effects of Chitosan against Bisphenol- A Induced Endocrine Toxicity and Androgen Receptor Gene Expression Changes in Male Rats

Bisphenol A (BPA) is an endocrine disruptor which can mimic estrogen and has been shown to cause negative health effects in animal studies. The aim of this work was to study the protective effect of chitosan against BPA. Forty male albino rats were randomly divided into four equal groups. Group I, animals served as control. Group II, animals were injected by bisphenol A, intra-peritoneal, at a dose of 5 mg/kg body weight daily for 3 weeks. Group III, animals were gavaged with chitosan at a dose of 30 mg/kg body weight for 3 weeks. Group IV, animals were injected by bisphenol A, intra-peritoneal, at a dose of 5 mg /kg body weight and after two hours animals were gavaged with chitosan at 30 mg/kg body weight for 3 weeks. At the end of the experiment, blood samples were taken for subsequent biochemical analyses. Testosterone, estradiol, AST, ALT, alkaline phosphatase (Alk. ph.), bilirubin, plasma glutathione peroxidase (GPx) and malondialdehyde (MDA) were determined. In addition, sperm abnormalities, expression of androgen receptor (AR) gene in testis tissues and caspase 3 activity in liver samples were evaluated. Testis and liver specimens were dissected for histopathological examination. The results indicated a decrease in testosterone hormone level while estradiol increased after rats were injected by BPA. However, chitosan treatment restored the testosterone level. It was apparent that BPA caused dysfunction to hormonally regulated body systems. However, chitosan treatment adjusted the metabolic functions and controled fertility. The levels of AST, ALT, Alk. ph. bilirubin and (MDA) enzymes were significantly increased while glutathione peroxidase was significantly decreased in group II after injection with BPA. Chitosan treatment counteracted the effects of BPA. Chitosan decreased the liver inflammation and necrosis. Moreover, the results indicated that the frequency of the sperm abnormalities, induced by BPA treatment, decreased significantly with chitosan administration compared with BPA treatment alone. Also, the expression of AR gene was up-regulated significantly with chitosan treatment combined with BPA compared with BPA treatment alone. Furthermore, the high level of caspase-3 activity induced by BPA in liver tissues was significantly decreased with chitosan treatment compared with BPA treatment alone. Histopathological analysis indicated that BPA induced testis tissues degeneration as well as liver apoptosis and necrosis. Chitosan treatment ameliorated testis and liver damage. In conclusion, chitosan seams to act as an antioxidant against toxicity of the endocrine system, sperm abnormalities, alteration in the AR gene expression and liver apoptosis. The potential biological effect of chitosan may be due to its active ingredients.