The Protective Effect of Metformin against Oxandrolone-Induced Infertility in Male Rats

2020 ◽  
Vol 26 ◽  
Author(s):  
Abdulqader Fadhil Abed ◽  
Yazun Bashir Jarrar ◽  
Hamzeh J Al-Ameer ◽  
Wajdy Al-Awaida ◽  
Su-Jun Lee

Background: Oxandrolone is a synthetic testosterone analogue that is widely used among bodybuilders and athletes. However, oxandrolone causes male infertility. Recently, it was found that metformin reduces the risk of infertility associated with diabetes mellitus. Aim: This study aimed to investigate the protective effects of metformin against oxandrolone-induced infertility in male rats. Methods: Rats continuously received one of four treatments (n=7) over 14 days: control DMSO administration, oxandrolone administration, metformin administration, or co-administration of oxandrolone and metformin. Doses were equivalent to those used for human treatment. Subsequently, testicular and blood samples were collected for morphological, biochemical, and histological examination. In addition, gene expression of the testosterone synthesizing enzyme CYP11A1 was analyzed in the testes using RT-PCR. Results: Oxandrolone administration induced male infertility by significantly reducing relative weights of testes by 48%, sperm count by 82%, and serum testosterone levels by 96% (ANOVA, P value < 0.05). In addition, histological examination determined that oxandrolone caused spermatogenic arrest which was associated with 2-fold downregulation of testicular CYP11A1 gene expression. However, co-administration of metformin with oxandrolone significantly ameliorated toxicological alterations induced by oxandrolone exposure (ANOVA, P value < 0.05). Conclusion: Metformin administration protected against oxandrolone-induced infertility in male rats. Further clinical studies are needed to confirm the protective effect of metformin against oxandrolone-induced infertility among athletes.

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Hadeel A. Al-Rawaf ◽  
Sami A. Gabr ◽  
Ahmad H. Alghadir

Background. Therapeutic strategies based on herbal plants and diets containing sufficient amounts of antioxidants and essential vitamins are very important factors in treating reproduction and male infertility worldwide. Thus, the aim of this study was to investigate the potential effects of Kaempferia parviflora (KP) on the role of some microRNAs in treated and nontreated infertile rats. In addition, the correlation of expressed microRNAs with sperm count, sperm motility, and sperm viability was identified. The probable use of these microRNAs as a diagnostic marker for predicting the clinical response of infertility to the treatment with KP was also achieved. Methods. In the present study, the potential effects of Kaempferia parviflora (KP) at different doses (140, 280, and 420 mg/kg) for six weeks on male rats with subinfertility were explored. In addition, the effect of KP on the expression of circulating microRNAs and its correlation with the parameters of sexual infertility was identified by performing both in vitro and in vivo assays. In vitro antioxidant activity, sperm functional analysis, serum testosterone, and expression of circulating microRNAs were conducted using colorimetric, ELISA, and real-time RT-PCR analysis, respectively. Results. Kaempferia parviflora (KP) at nontoxic doses of 140–420 mg/kg/day for six weeks significantly improved serum testosterone and epididymal sperm parameters (sperm count, motility, and sperm viability), increased testicular weight, and provided a reduction in the percentage of abnormal spermatozoon in infertile male rats. The expression of miR-328 and miR-19b significantly decreased, and miR-34 significantly increased in infertile rats treated with KP compared to infertile nontreated rats. After six weeks of KP therapy, the change in the expression levels of miRNAs was correlated positively with higher levels of serum testosterone and the measures of epididymal sperm parameters. The respective area under the receiver operating characteristic curve (AUC-ROC) was applied to predict the potential use of miR-328, miR-19b, and miR-34 in the diagnosis of male infertility in treated and nontreated infertile male rats. The data showed that AUC cutoff values of 0.91 for miR-328, 0.89 for miR-19b, and 0.86 for miR34 were the best estimated values for the clinical diagnosis of male rats with infertility. In rats treated with KP for six weeks, AUC cutoff values of 0.76 for miR-328, 0.79 for miR-19b, and 0.81 for miR-34 were the best cutoff values reported for the clinical response of infertility to KP therapy after six weeks. Conclusions. In this study, the improvement of male infertility might proceed via antioxidant and antiapoptotic pathways, which significantly improve spermatogenesis and aphrodisiac properties of males. In addition, the expression of miRNAs, miR-328, miR-34, and miR-19b, in KP-treated and nontreated infertile rats significantly correlated with increased serum testosterone levels and epididymal sperm parameters as well. MicroRNAs, miR-328, miR-34, and miR-19b, might be related to oxidative and apoptotic pathways that proceeded in spermatogenesis. Thus, the use of miRNAs could have a role as diagnostic, therapeutic, and predictive markers for assessing the clinical response of Kaempferia parviflora treatment for six weeks. This may have potential applications in the therapeutic strategies based on herbal plants for male infertility. However, in subsequent studies, the genetic regulatory mechanisms of the expressed miRNAs should be fully characterized.


2020 ◽  
Vol 21 (1) ◽  
pp. 31-35
Author(s):  
Basma El-Desoky ◽  
Shaimaa El-Sayed ◽  
El-Said El-Said

Objective: Investigating the effect of green tea extract (GTE) on the testicular damage induced by cadmium chloride CdCl2 in male rats. Design: Randomized controlled study. Animals: 40 male Wistar rats. Procedures: Rats were randomly divided into four groups: A) control group (each rat daily received pellet diet); B) GTE group each rat daily received pellet diet as well as 3 ml of 1.5 % w/v GTE, C) CdCl2 group each rat was I/P injected a single dose of 1 mg/kg CdCl2, then daily received pellet diet, and D) CdCl2+GTE group each rat was I/P injected a single dose of 1 mg/kg CdCl2 then daily received pellet diet as well as 3 ml of 1.5 % w/v GTE. After 30 days, blood samples were collected for hormonal assays (testosterone, FSH, and LH). In addition, both testes were collected; one of them was used for quantification of 17-beta hydroxysteroid dehydrogenase III (17β-HSDIII) gene expression using a real-time PCR. The other testis was used for determination of catalase and reduced glutathione; GSH, Nitric oxide (NO) and malondialdehyde (MDA) levels. Results: CdCl2 decreased serum testosterone levels and its synthesis pathway (17β-HSDIII testicular gene expression). While antioxidants catalase and GSH were reduced, oxidants MDA were enriched in the testes of CdCl2-poisoned rats. This CdCl2-promoted testicular dysfunction was corrected via the administration of GTE to male rats. Conclusion and clinical relevance: GTE could be used as a remedy for protecting against CdCl2-induced testicular damage in male rats.


Author(s):  
Gabriel O. Oludare ◽  
Gbenga O. Afolayan ◽  
Ganbotei G. Semidara

Abstract Objectives This study aimed to access the protective effects of d-ribose-l-cysteine (DRLC) on cyclophosphamide (CPA) induced gonadal toxicity in male rats. Methods Forty-eight male Sprague-Dawley rats were divided into six groups of eight rats each. Group I the control, received distilled water (10 ml/kg), Group II received a single dose of CPA 100 mg/kg body weight intraperitoneally (i.p), Groups III and IV received a single dose of CPA at 100 mg/kg (i.p) and then were treated with DRLC at 200 mg/kg bodyweight (b.w) and 400 mg/kg b.w for 10 days, respectively. Rats in Groups V and VI received DRLC at 200 and 400 mg/kg b.w for 10 days, respectively. DRLC was administered orally. Results Results showed that CPA increased percentage of abnormal sperm cells and reduced body weight, sperm count, sperm motility, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels (p<0.05). CPA also induced oxidative stress as indicated by the increased malondialdehyde (MDA) content and reduced activities of the oxidative enzymes measured (p<0.05). Liver enzymes were elevated while the blood cells production was decreased in the rats administered CPA. DRLC supplementation enhanced the antioxidant defence system as indicated in the reduced MDA levels and increased activities of the antioxidant enzymes when compared with CPA (p<0.05). Bodyweight, sperm count, sperm motility, FSH, and testosterone levels were increased in the CPA + DRLC II group compared with CPA (p<0.05). Conclusions The results of this present study showed that DRLC has a potential protective effect on CPA-induced gonadotoxicity.


Author(s):  
Hozaifa K. Elsawah ◽  
Mohamed M. Kandiel ◽  
Aziza A. Amin ◽  
Haitham M. Mokhimar ◽  
AbuBakr M. El Mahmoudy

Background: Many drugs are implicated in male infertility and screening for medication history is an important for diagnosis and treatment of the problem. The aim is to study amikacin effect on male reproductive system in comparison to gentamicin.Methods: Twenty-five male wister rats weighted 220±20 gm and aged 8 weeks were randomly divided into five groups of five. The first group received gentamicin in dose 18.25 mg/kg/day once daily (OD) (therapeutic dose). The second group received gentamicin with double dose of the first group. The third group received amikacin in dose 54.75 mg/kg/day OD (therapeutic dose). The Fourth group received amikacin with double dose of the third group. However, the fifth group served as a control and received normal saline (NS) OD. All treatments were administered intraperitoneally (IP) for 14 days. On the 15th day, blood samples and reproductive organs were obtained from all animals. Testicular tissues were prepared for genetic testing and chemical and microscopical examination.Results: Amikacin and gentamicin negatively affected reproductive organs weights, sperm parameters, serum follicle stimulating hormone and luteinizing hormone (LH) level relative to control (p<0.05). However, serum testosterone level was only affected with gentamicin (p<0.05). A significant difference between gentamicin and amikacin was found in sperm count, testis and epididymis weights and serum testosterone and LH level (p<0.05). Testicular histopathological changes were also found with the two drugs with different degrees. Effects of both gentamicin and amikacin were dose-dependent.Conclusions: Both gentamicin and amikacin adversely affect andrological function that should be monitored and controlled during application of these drugs.


2011 ◽  
Vol 28 (7) ◽  
pp. 655-662 ◽  
Author(s):  
Mohamed Makni ◽  
Yassine Chtourou ◽  
Mohamed Barkallah ◽  
Hamadi Fetoui

This study investigated the protective effects of vanillin against acute brain damage induced by carbon tetrachloride (CCl4) in rats. The study was performed on 32 male rats divided into four groups: a control group, vanillin group ([Va] 150 mg/kg/day, intraperitoneally [i.p.]) and CCl4 toxication groups received a single injection of CCl4 (1 ml/kg, i.p.; CCl4 and Va + CCl4 groups). The degree of protection in brain tissue was evaluated by the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase, glutathione transferase, glutathione peroxidase and nitric oxide (NO). Vanillin showed a significant brain-protective effect by decreasing the level of lipid peroxidation and NO2 and elevated the activities of antioxidative enzymes and level of GSH. Consequently vanillin blocked oxidative brain damage induced by CCl4 in rats.


2013 ◽  
Vol 1 (1) ◽  
Author(s):  
Yusuf TS ◽  
Panti AA ◽  
Ekele BA ◽  
Nwobodo EI

Background: Male infertility can occur when sperms are limited innumber or function. Infertility is a socially destabilizing and stigmatizing condition for couples but in our society many erroneously believe it is a problem from the female alone. Objectives: To evaluate the semen of infertilemale partners of couplesattending gynaecological clinic of Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto. Methodology: This was a prospective study conducted at the gynaecological clinic of Usmanu Danfodiyo University Teaching Hospital Sokoto between 1stJanuary 2011 and 30th June 2011. For the purpose of this study all male partners of women who complained of inability to conceive after a period of a year or more of unprotected sexual intercourse were recruited into the study. Data was extracted and analyzed using SPSS (version 11). A P–value of less than 0.05 was considered significant. Results: There were 125 cases of male infertility recruited during the period. Majority of the male patients (51.2%) were aged 40 years and above. Considerable percentage of the patients (46.4%) presented with duration of Infertility of 5 years and above. The identified risk factors were a previous history of Urethral discharge (37.6%) and previous treatment of sexually transmitted infections (29.6%). Hypospermia (33%) and Asthenospermia (42.4%) were the commonest disorders of semen Parameters seen. Low sperm count was seen in (36.8%) of studysubjects, Azoospermia was observed in 8% while 16% of them had disorder of sperm morphology. Conclusion: The study shows that infertility is associated with relatively high rate of abnormal sperm volume, motility and count. In addition, genital tract infections are major associated factors. Therefore, efforts to address STIs through primary, secondary and tertiary preventive measures may make significant contributions to reducing the prevalence of male infertility in Sokoto State.


Author(s):  
Sama Salah Khalil ◽  
Joseph Amin Aziz ◽  
Ismail Ahmed Khadiga ◽  
nanees fouad el-malkey

N-acetylcysteine (NAC) and melatonin were reported to exert protective effects on testicular tissues. Thus, this study aimed to determine which of these is more efficient against obesity-induced testicular dysfunction in albino rats. Total 32 adult male rats (195 ± 10g) were divided into 4 groups: control, obese rats fed a high-fat diet (HFD), HFD+ NAC (150 mg/kg/d, ip) and HFD+melatonin (10 mg/kg/d, ip) group, for five weeks. Testes and epididymis were weighted. Lipid profile, pituitary-testicular hormones, tumor necrosis factor-α (TNFα), epididymal sperm parameters, testicular oxidant/antioxidant system, testicular and the epididymal histopathology, immunohistochemical localization for androgen receptors (AR) and Bax reaction were analyzed. Administration of NAC or melatonin significantly improved the lipid parameters, gonadal hormones, TNFα level, sperm count and abnormal morphology, oxidant/antioxidant system and the absolute testicular and epididymal mass with an enhancement of testicular architecture, AR expression and apoptosis as compared to that in the obese group. Additionally, as compared to the NAC group, the melanin group had significantly reduced BMI, total cholesterol, triglyceride, and TNFα and increased testosterone, sperm count, motility, superoxide-dismutase activity, mitigated histo-morphometrical changes, BAX expression, and increased testicular AR expression. Therefore, melatonin was more efficient than NAC in affording fortification against HFD-induced testicular dysfunction


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3518-3518 ◽  
Author(s):  
M. J. O’Connell ◽  
S. Paik ◽  
G. Yothers ◽  
J. P. Costantino ◽  
J. W. Cowens ◽  
...  

3518 Background: As an initial step in developing abetter method of assessing prognosis following potentially curative surgery for colon cancer, we performed an exploratory gene identification study. Methods: RNA was extracted from three 10-micron sections of the FPE tumor tissue obtained at the initial diagnosis from 353 patients entered between 1977 and 1984 into the surgery-only or surgery-plus BCG arms of NSABP C-01/C-02. Expression was quantified for 757 cancer-related and reference genes with RT-PCR. Results: Blocks from 270 patients were evaluable after pre-specified exclusions: 128 were stage II and 142 were stage III. All patients had ≥ 5-year follow up. In univariate Cox proportional hazard analyses, 148 genes exhibited a nominally significant (unadjusted p-value <0.05) linear association with recurrence-free interval (RFI) (7 genes p≤0.001, 66 genes 0.001<p<0.01; 75 genes 0.01≤p<0.05). False discovery rate calculations suggest that about 25% of the 148 genes are expected to be false positives. Higher expression was associated with shorter RFI for 118 genes including SERPINB5, DUSP1, AKT3, TIMP1, ANXA2, RHOB (p≤ 0.001) and with longer RFI for 30 genes including BRCA1 (p≤0.001). The relationship between gene expression and RFI was similar for stage II and stage III patients for 143 of the 148 genes found to be significant. The largest cluster of genes is functionally related to extracellular matrix remodeling. The magnitude of the hazard ratios is similar to that observed in the early Oncotype DX studies in breast cancer and should allow clinically useful separation into low/intermediate/high risk groups. Conclusions: Quantitative RT-PCR assay of FPE colon cancer tissue can be used to identify large numbers of genes associated with RFI in patients with stage II and III colon cancer. If these results are confirmed by additional studies in progress, this technique has promise to improve selection of colon cancer patients for adjuvant chemotherapy. Funded in part as a collaborative arrangement under contract between the NSABP Foundation, Inc., and Genomic Health, Inc. [Table: see text]


2014 ◽  
Vol 33 (3) ◽  
pp. 155-161 ◽  
Author(s):  
Ch. Supriya ◽  
B. P. Girish ◽  
P. Sreenivasula Reddy

Aflatoxin B1 (AFB1), one of the most common mycotoxins found in human foods, is principally hepatotoxic; however, it also affects reproduction. The aim of the present study was to elucidate the reproductive toxic effects and possible mechanism of action of AFB1 in rats. Male Wistar rats were injected intramuscularly with doses of 10, 20, or 50 µg AFB1/kg body weight on alternate days from 45 to 100 days of age. Significant reductions in body weights, relative weights of reproductive organs, daily sperm production, epididymal sperm count, viable sperm, motile sperm, and hypoosmotic swelling-tail coiled sperm were observed. Significant decreases in testicular steroidogenic enzymes and serum testosterone levels were also observed indicating decreased steroidogenesis. In silico docking studies illustrated AFB1 binds with steroidogenic acute regulatory (StAR) protein thereby affecting the transport of cholesterol into mitochondria resulting in decreased steroidogenesis.


Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1268
Author(s):  
Jiacheng Zhang ◽  
Zhaoran Zhang ◽  
Jianfeng Xu ◽  
Chun Ye ◽  
Shulin Fu ◽  
...  

Glaesserella parasuis (G. parasuis) causes inflammation and damage to piglets. Whether polyserositis caused by G. parasuis is due to tight junctions damage and the protective effect of baicalin on it have not been examined. Therefore, this study aims to investigate the effects of baicalin on peritoneal tight junctions of piglets challenged with G. parasuis and its underlying molecular mechanisms. Piglets were challenged with G. parasuis and treated with or without baicalin. RT-PCR was performed to examine the expression of peritoneal tight junctions genes. Immunofluorescence was carried out to detect the distribution patterns of tight junctions proteins. Western blot assays were carried out to determine the involved signaling pathways. Our data showed that G. parasuis infection can down-regulate the tight junctions expression and disrupt the distribution of tight junctions proteins. Baicalin can alleviate the down-regulation of tight junctions mRNA in peritoneum, prevent the abnormalities and maintain the continuous organization of tight junctions. Our results provide novel evidence to support that baicalin has the capacity to protect peritoneal tight junctions from G. parasuis-induced inflammation. The protective mechanisms of baicalin could be associated with inhibition of the activation of PKC and MLCK/MLC signaling pathway. Taken together, these data demonstrated that baicalin is a promising natural agent for the prevention and treatment of G. parasuis infection.


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