Fahad Kabeer, Shaista Anjum, Atique Ahmed Behan, Muhammad Usman, Nazima Yousaf khan, Muhammad Azeem, Hafiz Misbah Ud Din, Muhammad Adeel Arshad, Sadaf Nazir, Shiping Cheng, Jameel Ahmed Buzdar
{"title":"山奈酚通过nrf2介导的抗氧化和凋亡调节，减轻氯氰菊酯诱导的大鼠生殖毒性，有组织病理学证据：体内和硅细胞研究","authors":"Fahad Kabeer, Shaista Anjum, Atique Ahmed Behan, Muhammad Usman, Nazima Yousaf khan, Muhammad Azeem, Hafiz Misbah Ud Din, Muhammad Adeel Arshad, Sadaf Nazir, Shiping Cheng, Jameel Ahmed Buzdar","doi":"10.1007/s10735-025-10554-9","DOIUrl":null,"url":null,"abstract":"<div><p>Cypermethrin (CYP), a common synthetic pyrethroid pesticide, is associated with oxidative stress-mediated female reproductive toxicity. With increasing concern over reproductive failures, exploring natural alternatives to mitigate this problem is crucial. For this purpose, thirty–six female SD rats were divided into six different (<i>n</i> = 6) groups such as negative control (group I), while disease control (group II) was treated to CYP-induced toxicity. Group III received 5 mg/kg Clomiphene Citrate, a standard drug, and groups IV, V, and VI were subjected with Kaempferol (KAE) dosage of 25, 50 and 100 mg/kg, respectively, for 14 days after induction of toxicity. CYP exposure significantly impaired the fertility status of female rats, disrupted the estrous cycle, altered ovarian and uterine coefficients. It also reduced antioxidant enzyme activity while elevating malondialdehyde levels. KAE supplementation effectively reversed these changes by restoring fertility status, normalizing antioxidant enzyme activity and reducing MDA levels, and improving ovarian and uterine coefficients. Histopathological analysis revealed preserved uterine and ovarian integrity in KAE-treated groups. Furthermore, KAE regulated the mRNA expression of key apoptotic and oxidative stress markers including Bcl2, Bax, caspase-3, caspase-9, and Nrf2. Further, gene ontological study revealed that these genes are involved in apoptotic signaling, immune homeostasis and neuronal regulation due to strong enrichment in mitochondrial and protease related function. Molecular docking analysis demonstrated that KAE exhibited significantly, inhibit Nrf2-KEAP1 bonding compared to Clomiphene citrate, indicated by well docking score. It is concluded that KAE holds therapeutic potential as a safe, natural alternative to combat CYP induced oxidative stress, apoptosis, and reproductive toxicity.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Kaempferol alleviates cypermethrin induced reproductive toxicity in rats via Nrf2-mediated antioxidant and apoptotic regulation with histopathological evidence: in vivo and in silico study\",\"authors\":\"Fahad Kabeer, Shaista Anjum, Atique Ahmed Behan, Muhammad Usman, Nazima Yousaf khan, Muhammad Azeem, Hafiz Misbah Ud Din, Muhammad Adeel Arshad, Sadaf Nazir, Shiping Cheng, Jameel Ahmed Buzdar\",\"doi\":\"10.1007/s10735-025-10554-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Cypermethrin (CYP), a common synthetic pyrethroid pesticide, is associated with oxidative stress-mediated female reproductive toxicity. With increasing concern over reproductive failures, exploring natural alternatives to mitigate this problem is crucial. For this purpose, thirty–six female SD rats were divided into six different (<i>n</i> = 6) groups such as negative control (group I), while disease control (group II) was treated to CYP-induced toxicity. Group III received 5 mg/kg Clomiphene Citrate, a standard drug, and groups IV, V, and VI were subjected with Kaempferol (KAE) dosage of 25, 50 and 100 mg/kg, respectively, for 14 days after induction of toxicity. CYP exposure significantly impaired the fertility status of female rats, disrupted the estrous cycle, altered ovarian and uterine coefficients. It also reduced antioxidant enzyme activity while elevating malondialdehyde levels. KAE supplementation effectively reversed these changes by restoring fertility status, normalizing antioxidant enzyme activity and reducing MDA levels, and improving ovarian and uterine coefficients. Histopathological analysis revealed preserved uterine and ovarian integrity in KAE-treated groups. Furthermore, KAE regulated the mRNA expression of key apoptotic and oxidative stress markers including Bcl2, Bax, caspase-3, caspase-9, and Nrf2. Further, gene ontological study revealed that these genes are involved in apoptotic signaling, immune homeostasis and neuronal regulation due to strong enrichment in mitochondrial and protease related function. Molecular docking analysis demonstrated that KAE exhibited significantly, inhibit Nrf2-KEAP1 bonding compared to Clomiphene citrate, indicated by well docking score. It is concluded that KAE holds therapeutic potential as a safe, natural alternative to combat CYP induced oxidative stress, apoptosis, and reproductive toxicity.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":650,\"journal\":{\"name\":\"Journal of Molecular Histology\",\"volume\":\"56 5\",\"pages\":\"\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-08-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Histology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s10735-025-10554-9\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Histology","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s10735-025-10554-9","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Kaempferol alleviates cypermethrin induced reproductive toxicity in rats via Nrf2-mediated antioxidant and apoptotic regulation with histopathological evidence: in vivo and in silico study
Cypermethrin (CYP), a common synthetic pyrethroid pesticide, is associated with oxidative stress-mediated female reproductive toxicity. With increasing concern over reproductive failures, exploring natural alternatives to mitigate this problem is crucial. For this purpose, thirty–six female SD rats were divided into six different (n = 6) groups such as negative control (group I), while disease control (group II) was treated to CYP-induced toxicity. Group III received 5 mg/kg Clomiphene Citrate, a standard drug, and groups IV, V, and VI were subjected with Kaempferol (KAE) dosage of 25, 50 and 100 mg/kg, respectively, for 14 days after induction of toxicity. CYP exposure significantly impaired the fertility status of female rats, disrupted the estrous cycle, altered ovarian and uterine coefficients. It also reduced antioxidant enzyme activity while elevating malondialdehyde levels. KAE supplementation effectively reversed these changes by restoring fertility status, normalizing antioxidant enzyme activity and reducing MDA levels, and improving ovarian and uterine coefficients. Histopathological analysis revealed preserved uterine and ovarian integrity in KAE-treated groups. Furthermore, KAE regulated the mRNA expression of key apoptotic and oxidative stress markers including Bcl2, Bax, caspase-3, caspase-9, and Nrf2. Further, gene ontological study revealed that these genes are involved in apoptotic signaling, immune homeostasis and neuronal regulation due to strong enrichment in mitochondrial and protease related function. Molecular docking analysis demonstrated that KAE exhibited significantly, inhibit Nrf2-KEAP1 bonding compared to Clomiphene citrate, indicated by well docking score. It is concluded that KAE holds therapeutic potential as a safe, natural alternative to combat CYP induced oxidative stress, apoptosis, and reproductive toxicity.
期刊介绍：
The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes.
Major research themes of particular interest include:
- Cell-Cell and Cell-Matrix Interactions;
- Connective Tissues;
- Development and Disease;
- Neuroscience.
Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance.
The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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