Protective effect of orange and grapefruit peel extracts against testicular toxicity induced by sulfasalazine in male albino rats

Sulfasalazine is a drug commonly used for the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. However, the histological changes in the testes are not well defined. Also, orange and grapefruit peels are powerful antioxidants that have come into use recently for the treatment of infertility. This study aimed to elucidate the histological, immunohistochemical, and ultrastructural changes in the testes after sulfasalazine treatment and evaluate the possible protective role of orange and grapefruit peel extracts. This study included 48 adult male albino rats divided into six equal groups: the control group [group I]; the orange peel extract group [group II]; the grapefruit peel extract group [group III]; the sulfasalazine group [group IV]; the sulfasalazine and orange peel extract group [group V]; and the sulfasalazine and grapefruit peel extract group [group VI]. At the end of the experiment [2 weeks], all animals were sacrificed and their testes were excised. Paraffin sections were prepared and stained with H and E and immunohistochemical staining was performed for proliferating cell nuclear antigen. Other pieces of the testis were used for ultrastructural study. Sulfasalazine was shown to affect the testes. The changes were in the form of irregular degenerated seminiferous tubules, germ cells, decrease in proliferating cell nuclear antigen, ultrastructural alterations of spermatogenic cells, and thickened basement membranes. These changes were present in some tubules in the testes. Treatment with orange or grapefruit peel extracts proved to improve these changes. Sulfasalazine has deleterious effects on the structure of the testes and supplementation with orange or grapefruit peel extracts with sulfasalazine can overcome the toxicity of sulfasalazine on the testis and protect testicular tissue from the detrimental effects of sulfasalazine

Reversible germ cell toxicity of sulphasalazine and ampicillin combination in male rats

The antifertility effect of ampicillin [AMP, 40 mg/kg] and sulphasalazine or salicylazosulfapyridine [SASP, 300, 450 and 600 mg/kg] in male rats has been reported earlier. The combination of AMP and SASP is generally used in certain pathological conditions, but the combined effect of these two drugs on the fertility is not clear. So, the aim of this study was to investigate the antifertility effect of ampicillin and sulphasalazine combination in male rats. In the present study, forty rats were randomly divided into five groups [n=8]. Group 1 served as the control, while Group 2 and 3 received AMP and SASP at the doses of 20 mg/kg and 200 mg/kg respectively. Moreover, group 4 and 5 received the combination of SASP [100 mg/kg] and AMP [10 mg/kg]. However, for evaluating the reversible effect of the combination, a washout period of 30 days was given in group 5. After 45 days of drug treatment, each rat was sacrificed. The testes, seminal vesicles and epididymis were dissected and weighed. Furthermore, fertility tests, sperm characteristic analysis, histopathological studies, testosterone assay and tissue biochemistry were performed. The data were analyzed using ANOVA and in case ANOVA shows statistical differences, post hoc analysis was performed. A decrease in parameters related to fertility of males such as sperm count, sperm motility, fertility ratio, serum testosterone level, glycogen and protein content in sexual organs was observed. Although AMP and SASP significantly [p<0.001] reduced the reproductive activity separately, but their combination was found to be impairing the reproductive activity at a considerably lower dose. However, on withdrawing the treatment, all these parameters were restored which was confirmed by the histopathological analysis of the testis. The combination produces synergistic antifertility effect in male rats and the effect was reversible. The dose and efficacy of results could be extrapolated in future clinical trials