Molecular Mechanisms Contributing to the Impairment of Steroid Hormones, Sperm Characteristics, and Testicular Architecture in Male Rabbits After Chronic Exposure to Cadmium: Role of Gallic Acid and Selenium as Antioxidants.

Abstract

One hazardous material that occurs naturally in the environment and induces oxidative stress is cadmium (Cd). Epidemiological data revealed that exposure to cadmium in the workplace and environment might be linked to many illnesses and serious testicular injuries.

Aims: It is taught that antioxidants can protect different organs against environmental toxic compounds. Therefore, the current investigation aims to show the role of antioxidants (gallic acid and selenium) in the protection against cadmium toxicity, including the architecture of the testes, semen properties, steroid hormones, protein expression of cytochrome P450 [CYP 19 and 11A1] contributing to the production of steroid hormones, and antioxidant enzyme activities, in male rabbits.

Methods: Male rabbits were given cadmium orally three times/week [1 mg/kg BW] for twelve weeks. In addition, gallic acid (20 mg/kg) or selenium (1 mg/kg BW) was administered two hours before cadmium treatment. This investigation included a spectrophotometer, histopathology, and Western immunoblotting techniques.

Results: Cadmium treatment significantly reduced sperm counts, testosterone, and estrogen levels after four, eight, and twelve weeks of treatment. In addition, after a 12-week treatment of rabbits with cadmium, the activity of 17β-hydroxysteroid dehydrogenase and antioxidant enzymes, including catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, and glutathione S-transferase, as well as the glutathione levels, were inhibited in the testes tissue. On the other hand, following cadmium treatment, rabbit's testes showed a discernible increase in free radical levels. Interestingly, the activity of antioxidant enzymes and level of free radicals were recovered in rabbits treated with gallic acid or selenium before cadmium treatment. In addition, after 12 weeks of cadmium treatment, the steroidogenic protein expressions of CYP 11A1 and CYP 19 were upregulated and downregulated in the testes, respectively. Interestingly, after pretreatment of rabbits with either gallic acid or selenium for two hours before cadmium administration, the downregulated CYP11A1 was restored to normal levels. In the histopathological investigation, immature spermatozoids and sloughed spermatogonium cells were observed in cadmium-treated rabbits' testes. On the other hand, pretreatments of rabbits with gallic acid or selenium mitigated and alleviated the adverse effects of cadmium on testes architecture and increased the production of healthy sperm.

Conclusions: The lower levels of steroid hormones could be due to the downregulation of CYP11A1, inhibition of 17β-hydroxysteroid dehydrogenase, antioxidant enzyme activities, and the induction of free radical levels. Furthermore, the pretreatment of rabbits with gallic acid or selenium mitigated the adverse effects of cadmium on the tissue architecture of testes and steroid hormone levels.