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吡咯并[3,4 -]哒嗪酮的1,3,4 - 恶二唑衍生物可减轻三硝基苯磺酸诱导的结肠炎且无明显睾丸毒性。

1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-]pyridazinone Alleviate TNBS-Induced Colitis and Exhibit No Significant Testicular Toxicity.

作者信息

Merwid-Ląd Anna, Ziółkowski Piotr, Nowak Beata, Świątek Piotr, Szczukowski Łukasz, Kwiatkowska Joanna, Piasecka Katarzyna, Szeląg Adam, Szandruk-Bender Marta

机构信息

Department of Pharmacology, Wroclaw Medical University, Mikulicza-Radeckiego 2, 50-345 Wrocław, Poland.

Department of Clinical and Experimental Pathology, Wroclaw Medical University, Marcinkowskiego 1, 50-368 Wrocław, Poland.

出版信息

Pharmaceuticals (Basel). 2025 Apr 8;18(4):546. doi: 10.3390/ph18040546.

Abstract

Inflammatory bowel disease significantly impairs the patient's quality of life. In young individuals, both the disease and the drugs used for the treatment may impact fertility. Our study aimed to assess the action of new 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone on the rat testes in a model of TNBS-induced colitis in rats. In the current study, testes from eight randomly chosen rats were taken from each of the following groups: the control group (K), the colitis group (C), and the groups receiving compounds 7b, 10b, and 13b in higher doses (20 mg/kg). Colitis did not affect the testicular index (expressed as a percentage of the body weight), but in group 13b, this parameter was significantly higher than in group K. No significant differences between groups were noticed in malondialdehyde, superoxide dismutase, interleukin-1, or metalloproteinase 9 levels. In the colitis group, lactate dehydrogenase activity in the testes was not increased; however, the administration of compound 10b significantly increased this parameter when compared to both groups K and C. Histological evaluation also did not reveal abnormalities, and the morphology of the testicular tissues was comparable in all groups. The results may suggest that the new 1,3,4-oxadiazole derivatives of pyrrolo[3,4-]pyridazinone did not exert significant testicular toxicity.

摘要

炎症性肠病严重损害患者的生活质量。在年轻个体中,该疾病以及用于治疗的药物都可能影响生育能力。我们的研究旨在评估吡咯并[3,4-d]哒嗪酮的新型1,3,4-恶二唑衍生物在大鼠三硝基苯磺酸诱导的结肠炎模型中对大鼠睾丸的作用。在本研究中,从以下每组中随机选取八只大鼠的睾丸:对照组(K)、结肠炎组(C)以及接受高剂量(20mg/kg)化合物7b、10b和13b的组。结肠炎并未影响睾丸指数(以体重的百分比表示),但在13b组中,该参数显著高于K组。在丙二醛、超氧化物歧化酶、白细胞介素-1或金属蛋白酶9水平上,各组之间未观察到显著差异。在结肠炎组中,睾丸中的乳酸脱氢酶活性未增加;然而,与K组和C组相比,给予化合物10b显著增加了该参数。组织学评估也未发现异常,且所有组中睾丸组织的形态学相当。结果可能表明,吡咯并[3,4-]哒嗪酮的新型1,3,4-恶二唑衍生物未产生显著的睾丸毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f809/12030013/d941338e6acf/pharmaceuticals-18-00546-g001.jpg

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