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Ebelik Bölümü Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12514/225

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    Article
    Chronic Maternal Tobacco Smoke Exposure and/or Alpha-Lipoic Acid Treatment Causes Long-Term Deterioration of Testis and Sexual Behavior in Adult Male Rats
    (Elsevier, 2020) Yardimc, Ahmet; Ramazan Fazil Akkoc, Ahmet Tektemur, Nazife Ulker, Nalan Kaya Tektemur, Elif Erdem Güzel, Sinan Canpolat, Ibrahim Enver Ozan
    Background: Tobacco use during pregnancy is known to have several negative effects on the offspring's reproductive health in the long term. The use of alpha-lipoic acid (ALA) as a dietary supplement during pregnancy has increased greatly in recent years and has been known to have positive effects on various pregnancy outcomes including miscarriage, diabetic embryopathy, preterm delivery, and congenital malformations. Aim: To evaluate the effects of tobacco smoke exposure (TSE) on sexual behavior, reproductive parameters, and testicles in adult male rats and to reveal the possible role of ALA administration on these parameters. Methods: Pregnant rats (n = 7 per group) were treated with tobacco smoke (TS), ALA (20 mg/kg), and TS + ALA for a total of 11 weeks. The following parameters were compared with 8 control rats: puberty parameters, sexual behavior; levels of serum gonadotropins and testosterone, total antioxidant status, and total oxidant status; the expression of the apoptotic protease-activating factor-1 and caspase 9 mRNA levels in the testis; and assessment of immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling assay of testis. Main Outcome Measure: Sexual behavior, changes in puberty parameters, and hormonal and genetic alterations were the outcomes analyzed in this study. Results: Maternal TSE caused a significant decrease in the number of intromissions compared to the control group. Similarly, ALA decreased erectile function in sexual behavior by decreasing the number of intromissions and intromission ratio in the ALA group compared to the control group. In addition, TSE and ALA treatment caused an impairment of some consummatory sexual behaviors. Also, in parallel with this inhibitory effect, the age of pubertal onset was significantly delayed in the TS + ALA group compared to other groups. Also, histopathological changes in testicular tissue, oxidative stress markers, apoptotic index, and mRNA levels of apoptosis-related genes increased in all treatment groups. Clinical Implications: The use of ALA and/or tobacco products during pregnancy may adversely affect the reproductive health of male newborns in the long term. Strengths & Limitations: To the best of our knowledge, this study is the first to show the effects of maternal ALA treatment and/or TSE on the sexual behavior and reproductive parameters in male rats; however, the study is based on an animal model, and the present findings partially reflect the characteristics of human sexual behavior. Conclusion: Maternal TSE and/or ALA treatment may impair sexual behavior in adulthood in male rats because of testicular damage caused by oxidative stress during gonadal development. Yardimci A, Akkoc RF, Tektemur A, et al. Chronic Maternal Tobacco Smoke Exposure and/or Alpha-Lipoic Acid Treatment Causes Long-Term Deterioration of Testis and Sexual Behavior in Adult Male Rats. J Sex Med 2020;17:1835–1847.
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    Hesperetin may alleviate the development of doxorubicin-induced pulmonary toxicity by decreasing oxidative stress and apoptosis in male rats
    (Elsevier, 2021) Erdem Güzel, Elif; Kaya Tektemur, Nalan
    Doxorubicin (DOX) is one of the most widely used chemotherapeutic agents. However, it causes pulmonary toxicity which decreases its clinical use in human cancer therapy. The present study was undertaken to obtain an insight into the potential protective effect of hesperetin (HES) against doxorubicin-induced pulmonary toxicity in rats. The animals were divided into 4 groups with 7 rats per group. The experimental treatments were as follows: Control, DOX, DOX + HES, and HES groups. DOX was administered at the dosage of 15 mg/kg i.p for a single dose. HES was administered at the dosage of 50 mg/kg by oral gavage every other day. After 28 days, biochemical parameters, oxidative stress status, histopathological changes, apoptosis-related genes and apoptotic index (AI) were examined of lung tissue. Histopathological changes, Poly [ADP-ribose] polymerase 1 (PARP-1), Caspase-3 (Casp3), Cytochrome c (Cytc), apoptosis-related genes, and AI significantly increased in the DOX group relative to the control group. Malondialdehyde (MDA) significantly increased, while superoxide dismutase (SOD) and glutathione peroxidase (GPx) decreased in the DOX group relative to the control group. However, histopathological findings, MDA, AI, and PAPR1, Casp3 protein expression, mRNA expression of Cytc significantly decreased, while SOD, GPx increased in the DOX + HES group relative to the DOX group. These results attested HES might be a potential agent for the treatment of DOX-induced pulmonary toxicity.
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    The therapeutic effect of hesperetin on doxorubicin-induced testicular toxicity: Potential roles of the mechanistic target of rapamycin kinase (mTOR) and dynamin-related protein 1 (DRP1)
    (Elsevier, 2022) Tektemur, Ahmet; Kaya Tektemur, Nalan; Erdem Güzel, Elif
    Clinical utilization of doxorubicin (DOX), which is a commonly used chemotherapeutic, is restricted due to toxic effects on various tissues. Using hesperetin (HST), an antioxidant used in Chinese traditional medicine protects testis against DOX-induced toxicity although the molecular mechanisms are not well-known. The study was aimed to examine the possible role of the mechanistic target of rapamycin kinase (mTOR) and dynamin 1-like dynamin-related protein 1 (DRP1) in the therapeutic effects of HST on the DOX-induced testicular toxicity. Rats were divided into Control, DOX, DOX + HST, and HST groups (n = 7). Single-dose DOX (15 mg/kg) was administered intraperitoneally and HST (50 mg/kg) was administered by oral gavage every other day for 28 days. Total antioxidant status (TAS), histopathological evaluations, immunohistochemistry, and gene expression level detection analyses were performed. Histopathologically, DOX-induced testicular damage was ameliorated by HST treatment. DOX reduced testicular TAS levels and increased oxidative stress markers, 8-Hydroxy-deoxyguanosine (8-OHdG), and 4-Hydroxynonenal (4-HNE). Also, upregulated mTOR and DRP1 expressions with DOX exposure were decreased after HST treatment in the testis (p < 0.05). On the other hand, DOX-administration downregulated miR-150-5p and miR-181b-2-3p miRNAs, targeting mTOR and mRNA levels of beclin 1 (BECN1) and autophagy-related 5 (ATG5), autophagic markers. Furthermore, these levels were nearly similar to control testis samples in the DOX + HST group (p < 0.05). The study demonstrated that HST may have a therapeutic effect on DOX-induced testicular toxicity by removing reactive oxygen species (ROS) and by modulating the mTOR and DRP1 expressions, which have a critical role in regulating the balance of generation/elimination of ROS.