Vitamin B12 Supplement Exerts a Beneficial Effect on the Seminiferous Epithelium of Cimetidine-Treated Rats

Abstract

Treatment of gastric ulcer with cimetidine reduces acid secretion and interferes in the vitamin B₁₂ absorption. Regarding the harmful effect of cimetidine on the seminiferous tubules, the aim of the present study was to verify if prolonged treatment with cimetidine causes vitamin B₁₂ deficiency and whether the testicular damages are attenuated by vitamin B₁₂ supplementation. Adult male rats received, for 50 days, cimetidine (CMTG), cimetidine and vitamin B₁₂ (CMT/B₁₂G), vitamin B₁₂ (B₁₂G) and saline solution (CG). Vitamin B₁₂ and homocysteine plasma levels were evaluated and the testes were embedded in glycol methacrylate for the morphometric analyses of total, epithelial and luminal areas of the seminiferous tubules, number of Sertoli cells and frequencies of tubules according to stages and containing Sertoli and germ cells in the lumen. Terminal deoxynucleotidyl-transferase mediated dUTP nick end labeling (TUNEL) method and proliferating cell nuclear antigen (PCNA) immunohistochemistry were carried out. CMTG showed TUNEL-positive Sertoli cells and significant reductions in the epithelial and total tubular areas, number of Sertoli cells and frequency of tubules VII-VIII. In the CMT/B₁₂G, the number of Sertoli cells and the epithelial and total tubular areas were similar to CG. The number of Sertoli cells (in B₁₂G) and the frequency of tubules at stages VII-VIII (in B₁₂G and CMT/B₁₂G) increased significantly; PCNA-positive Sertoli cells were found in these groups. Although cimetidine was not able to induce vitamin B₁₂ deficiency, this drug causes tubular atrophy due to Sertoli cell damage and loss of germ cells. However, vitamin B₁₂ supplement is able to stimulate spermatogenesis and restore the number of Sertoli cells, softening the harmful effect of cimetidine on spermatogenesis.