The obligatory use of cytotoxic drugs to face the malignant tumors results in survivors that suffer from long term health problems. Fertility problems, especially in young boys, exert one of the major consequences of chemotherapy treatment that needs resolution. We investigate the potential effect of the cysteinyl leukotriene receptor antagonist montelukast on doxorubicin-induced testicular damage. Five groups of adult Wistar male rats were subjected to the following treatment; vehicle for the control group, montelukast (20 mg/kg orally daily for 10 days) for the drug control, doxorubicin (12 mg/kg intraperitoneal injection once at 5th day) for the toxic group, montelukast at 10 mg/kg + doxorubicin, montelukast at 20 mg/kg + doxorubicin. The period of the experiment was 10 days administration of montelukast, while doxorubicin was injected at the 5th day. Results of serum testosterone, testicular lipid peroxidation, antioxidant status, and histopathology revealed protection of montelukast against doxorubicin-induced testicular damage. The pro-apoptotic caspase 3 and the pro-inflammatory tumor necrosis factor-alpha were examined immunohistochemically and showed a significant decrease with montelukast treatment as compared to doxorubicin group. Doxorubicin increased gene expression of matrix metalloproteinase 9 and decreased peroxisome proliferator activated receptor gamma. Montelukast treatment restored their expressions to normal values. In conclusion, montelukast administration can ameliorate the testicular damage induced by doxorubicin based on its anti-inflammatory, antioxidant and anti-apoptotic effects as well as by of modulation of important genes expression.

中文翻译：

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白三烯受体拮抗剂孟鲁司特对阿霉素诱导的大鼠睾丸损伤的保护作用的潜在机制。

必须使用细胞毒性药物来面对恶性肿瘤，导致幸存者遭受长期健康问题的困扰。生育问题，特别是在年轻男孩中，是化学疗法需要解决的主要后果之一。我们调查半胱氨酰白三烯受体拮抗剂孟鲁司特对阿霉素诱导的睾丸损伤的潜在影响。五组成年Wistar雄性大鼠接受以下治疗：对照组的媒介物，孟鲁司特（每天口服20 mg / kg，连续10天）用于药物控制，阿霉素（第5天一次腹膜内注射12 mg / kg，第5天），孟鲁司特10 mg / kg +阿霉素，孟鲁司特20 mg / kg +阿霉素。实验期为孟鲁司特10天给药，而在第5天注射阿霉素。血清睾丸激素，睾丸脂质过氧化，抗氧化状态和组织病理学结果显示孟鲁司特对阿霉素诱导的睾丸损伤具有保护作用。免疫组化检查了促凋亡的半胱氨酸天冬氨酸蛋白酶3和促炎性肿瘤坏死因子-α，与阿霉素组相比，孟鲁司特治疗显着减少了凋亡。阿霉素可增加基质金属蛋白酶9的基因表达，并降低过氧化物酶体增殖物激活的受体γ。孟鲁司特治疗将其表达恢复到正常值。总之，孟鲁司特的抗炎作用可减轻阿霉素引起的睾丸损伤，