Effect of Aminoguanidine in Sperm DNA Fragmentation In Varicocelized Rats: Role of Nitric Oxide

Abbasi, Mehdi; Alizadeh, Rafieh; Abolhassani, Farid; Amidi, Fardin; Ragerdi, Kashani I.; Fazelipour, Simin; Hoshino, Yuko; E, Sato; Dehpour, Ahmad Reza

doi:10.1177/1933719110393028

Cited by 28 publications

(26 citation statements)

References 42 publications

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“…The same deterioration of sperm DNA integrity following varicocele induction in our study could be explained by OS pathologic mechanism. In this study, the finding of negative changes of chromatin structure in varicocele rats as increase in percentage of sperm staining by three methods AB, TB and AO compared to control group is compatible with previous studies (Abbasi et al., ; Bertolla et al., ; Enciso et al., ).…”

Section: Discussionsupporting

confidence: 93%

“…For stabilizing, the AO stain solution stored at 4°C in a dark bottle for 4 weeks. After staining, the slides were gently rinsed with distilled water and evaluated by a fluorescent microscope (Leitz, Germany) as described in a previous publication (Abbasi et al., ). Same examiner assessed 200 sperms on each slide with an evaluation period less than 40 s per field.…”

Section: Methodsmentioning

confidence: 99%

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Can Melissa officinalis improve chromatin structure and sperm parameters in a rat model of varicocele?

2018

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Excessive production of reactive oxygen species is a central mechanism in the pathology of varicocele; Melissa officinalis (MO) is a medicinal plant from the Lamiaceae family that has antioxidant activity. In this study, we have investigated the potential therapeutic effect of MO on sperm parameters and chromatin structure in varicocelised rat. Male Wistar rats were randomly assigned to control, sham, varicocele, MO treatment and placebo groups. Rats in varicocele, MO treatment and placebo groups underwent left varicocele induction. Following the operation, rats in placebo and MO treatment groups received normal saline or MO extract, daily for 10 weeks respectively. At 10 weeks after varicocele induction, sperm chromatin and parameters were evaluated in all groups. Chromatin structure was evaluated by aniline blue, acridine orange and toluidine blue staining. All three staining outcomes were increased in varicocele and placebo compared control (and sham) groups (p < 0.05). Sperm count, motility, morphology and vitality were decreased between varicocele and control (and sham) group (p < 0.05). Sperm parameters and chromatin staining (else AB staining) outcomes improve in MO treatment compared to varicocele and placebo groups (p < 0.05). These findings suggest that MO ameliorate the harmful effect of varicocele on sperm parameters and chromatin structure.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Can Melissa officinalis improve chromatin structure and sperm parameters in a rat model of varicocele?

2018

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“…For intervention studies, some rats ( n = 6) were administered i.p. injections of 30 or 50 mg/kg body weight AG 1 hour prior to the administration of MTX . Some rats ( n = 6) were administered with AG alone 30 or 50 mg/kg body weight intraperitoneally.…”

Section: Methodsmentioning

confidence: 99%

Activation of the mitochondrial apoptotic pathway contributes to methotrexate‐induced small intestinal injury in rats

Natarajan

Abraham

Kota³

2017

Cell Biochemistry & Function

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The efficacy of methotrexate (MTX), a commonly used chemotherapeutic drug, is limited by intestinal injury. As the mechanism of MTX-induced small intestinal injury is not clear, there is no definitive treatment for MTX-induced gastrointestinal injury. The present study investigates the role of mitochondrial apoptotic pathway in MTX-induced small intestinal injury and examines whether aminoguanidine is effective in preventing the damage. Eight Wistar rats were administered 3 consecutive i.p. injections of 7 mg/kg body wt. MTX. Some rats were pretreated with 30 mg or 50 mg/kg body wt. of aminoguanidine (n = 6 in each group). Protein expressions of cytochrome c, caspases 3 and 9, and PARP-1 were determined in the small intestines by immunohistochemistry and western blot. Mitochondrial pathway of apoptosis was activated in the small intestines of MTX-treated rats as evidenced by intense immunostaining for cyt c, caspases 9 and 3, and PARP-1 and mitochondrial release of cyt c, activation of caspases, and PARP-1 cleavage by Western blot. Immunofluorescence revealed increased nuclear localization of PARP-1. Aminoguanidine pretreatment ameliorated MTX-induced small intestinal injury in dose-dependent manner and inactivated the mitochondrial apoptotic pathway. Aminoguanidine may possess beneficial intestinal protective effects as an adjuvant co-drug against MTX intestinal toxicity during cancer chemotherapy. As the mechanism of MTX-induced small intestinal injury is not clear, there is no definitive treatment for MTX-induced gastrointestinal injury. The results of the present study show that the mitochondrial pathway of apoptosis plays a role in MTX-induced small intestinal injury as evidenced by cytochrome c release, activation of caspases 9 and 3, PARP-1 cleavage, and DNA fragmentation. Aminoguanidine (AG) pretreatment attenuates the severity of small-intestinal injury induced in rats by MTX treatment. The mechanisms of action of AG involve inhibition of iNOS, and mitochondrial pathway of apoptosis. It is suggested that aminoguanidine may possess beneficial intestinal protective effects as an adjuvant co-drug against MTX intestinal toxicity during cancer chemotherapy.

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“…The reference values used were taken from the criteria given by the Guidelines on Male Infertility 2010, provided by the European Association of Urology (EAU). The lower reference limit (with 5th centiles and their 95% confidence intervals) of progressive motility was 0.32 (0.31-0.34) and minimum sperm concentration was 15 Â 10 6 /ml (12)(13)(14)(15)(16) [25].…”

Section: Methodsmentioning

confidence: 99%

“…Increased levels of NO decrease the intratesticular level of androgens and also inhibit human chorionic gonadotropin hormone (hCG) steroidogenesis [12]. The sperm of infertile men with varicocele exhibit marked DNA damage that appears to be related to high oxidative stress [13][14][15]. The concentration of nitrotyrosine, a biological marker of NO-induced damage, in the spermatic veins is significantly higher than in the peripheral veins of patients with varicocele, indicating that NO causes nitration of plasma proteins with higher molecular weight.…”

Section: Introductionmentioning

confidence: 98%

Correlation between nitric oxide levels, the hypo-osmotic swelling test for sperm membranes and semen analysis in patients with varicocele

Pajovic

Radojević

Terzić

et al. 2013

Scandinavian Journal of Urology

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Effect of Aminoguanidine in Sperm DNA Fragmentation In Varicocelized Rats: Role of Nitric Oxide

Abstract: The findings of this study suggest that AG improves sperm DNA fragmentation that is associated with infertility in varicocelized rats, and treatment with AG can reduce the damage to sperm DNA.

Cited by 28 publications

References 42 publications

Can Melissa officinalis improve chromatin structure and sperm parameters in a rat model of varicocele?

Can Melissa officinalis improve chromatin structure and sperm parameters in a rat model of varicocele?

Activation of the mitochondrial apoptotic pathway contributes to methotrexate‐induced small intestinal injury in rats

Correlation between nitric oxide levels, the hypo-osmotic swelling test for sperm membranes and semen analysis in patients with varicocele

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