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1.
Toxicol Appl Pharmacol ; 433: 115772, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34715073

RESUMO

The cancer therapy using cyclophosphamide (CP) has been associated with adverse effects on the testicular function that raises concerns about the future fertility potential among cancer survivors. Curcumin, a polyphenol, has shown to possess a plethora of biological functions including tissue protective effects. In the present study, we investigated the protective effects of curcumin nanocrystals (NC) in mitigation of CP-induced testicular toxicity. Healthy adult (8-10 week) and prepubertal (2 week) male Swiss albino mice were injected with a single dose of CP (200 mg/kg) intraperitoneally (i.p). NC (4 mg/kg, i.p.) was administered every alternate day, for 35 days in adult mice while, a single dose of NC was injected intraperitoneally to prepubertal mice 1 h prior to CP. Administration of multiple doses of NC ameliorated CP-induced testicular toxicity in adult mice, which was evident from the improved sperm functional competence, sperm chromatin condensation, seminiferous tubule architecture and decreased apoptosis in testicular cells. Further, administration of NC 1 h prior to CP in prepubertal mice modulated the expression of genes pertaining to proliferation, pluripotency, DNA damage and DNA repair in spermatogonial cells at 24 h after the treatment. Overall, these results suggest that NC could be a promising chemoprotective agent, which can have potential application in male fertility preservation.


Assuntos
Antineoplásicos Alquilantes/toxicidade , Antioxidantes/farmacologia , Curcumina/farmacologia , Ciclofosfamida/toxicidade , Nanopartículas , Espermatogônias/efeitos dos fármacos , Doenças Testiculares/prevenção & controle , Testículo/efeitos dos fármacos , Animais , Antioxidantes/química , Proliferação de Células/efeitos dos fármacos , Curcumina/química , Dano ao DNA/efeitos dos fármacos , Composição de Medicamentos , Regulação da Expressão Gênica , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Infertilidade Masculina/prevenção & controle , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espermatogônias/metabolismo , Espermatogônias/patologia , Doenças Testiculares/induzido quimicamente , Doenças Testiculares/metabolismo , Doenças Testiculares/patologia , Testículo/metabolismo , Testículo/patologia , Fatores de Tempo
2.
Pestic Biochem Physiol ; 167: 104588, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32527428

RESUMO

Methyl parathion (MP) is a commonly used organophosphorus insecticide in commercial farming. It is well known that MP exposure can affect the function of nervous, respiratory, cardiovascular and reproductive systems. In our previous report we have demonstrated that MP exposure results in poor oocyte maturation and defective embryo development which is mainly mediated through oxidative stress. The present investigation was designed to explore whether using a potent free radical scavenger like Epigallocatechin-3-gallate (EGCG) can help in reducing the detrimental effects of MP on the oocytes. For the study, germinal vesicle (GV) stage oocytes collected from the ovaries of adult Swiss albino mice were subjected to in vitro maturation (IVM) in the presence or absence of MP (100 µg/mL) and/or EGCG (0.25 µM). MP significantly reduced the nuclear maturation rate, and resulted in poor cytoplasmic organization which was evident from the altered distribution pattern of mitochondria, endoplasmic reticulum and abnormal spindle organization. These changes were associated with significant elevation in oxidative stress and expression of ER stress markers such as 78 kDa Glucose regulated protein (GRP78) as well as X-box binding protein-1 (XBP1) in the oocytes. Further, the oocytes exposed to MP had lower activation rate and developmental potential. Supplementation of EGCG during IVM not only improved the nuclear maturation rate but also reduced the cytoplasmic abnormalities. These beneficial effects appear to be due to mitigation of oxidative and ER stress in oocytes. In conclusion, results of our study indicate that EGCG can help in alleviating MP-induced oocyte abnormalities.


Assuntos
Metil Paration , Animais , Catequina/análogos & derivados , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Camundongos , Oócitos , Estresse Oxidativo
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