Effects of telmisartan and losartan on irradiated testes

Mansano, Naira da Silva; Jorge, Isabela Fernandes; Chies, Agnaldo Bruno; Viani, Gustavo Arruda; Spadella, Maria Angélica

doi:10.1016/j.lfs.2017.12.031

Cited by 13 publications

(11 citation statements)

References 22 publications

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“…Thus, the data from this study suggest that by administering an intermediate dose of irradiation directly into the scrotum of the animals, associated with the treatment with losartan, the chances of survival of stem cells were potentiated and, with that, their regeneration and, subsequently, repopulation of seminiferous tubule from the resumption of spermatogenesis. Our previous study using the same experimental model, but exposing the testes to a dose of 5.0 Gy, reinforces that the kinetics of spermatogenesis is fundamental in the search for substances with radioprotective effects as, at this dose, testicular recovery was extremely compromised by excessive death of stem cells (30).…”

Section: Discussionsupporting

confidence: 72%

Losartan Attenuates Radiation-Induced Damage on Testes and Accelerates Tubular Regeneration

Santos

Alves

Chies

et al. 2022

Front. Reprod. Health

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Male germ cells are particularly susceptible to radiation; infertility being a common consequence after radiotherapy as it impairs spermatogenesis. This study aimed to test whether treatment with losartan (LOS), a selective antagonist of angiotensin II receptor subtype 1 (AT1R), can prevent or attenuate the acute and long-term radiation-induced damage to testes. Wistar rats were randomly distributed into six groups, three of which were studied on day 2 after irradiation: control (CTRL 2), irradiated non-treated (IR 2), and irradiated and treated with LOS (IRLOS 2); and three other groups that were studied on day 60 after irradiation: control (CTRL 60), irradiated non-treated (IR 60), and irradiated and treated with LOS (IRLOS 60). Seven consecutive days before and on the day of irradiation with 2.5 Gy directly administered in the scrotum, the animals were treated with LOS (34 mg/kg/two times/day). This treatment was continued 2 or 60 days after irradiation. The sperm quality was assessed from epididymis cauda. In addition, the testes were submitted to histopathological and morphometric-stereological analysis as well as the proliferating cell nuclear antigen (PCNA) quantification. Serum FSH and LH and plasma testosterone levels were also determined. The data obtained 2 days after the irradiation showed germ cell apoptosis, formation of vacuoles in the seminiferous epithelium, sloughing of germ cells into the lumen, and retention and phagocytosis of step-19 spermatids in Sertoli basal cytoplasm. The treatment with LOS in this period did not prevent or attenuate a radio-induced damage to the testes, illustrating that this drug does not protect against apoptosis derived from direct effects of radiation. On the other hand, 60 days after exposure, the data evidenced the deleterious effects of ionizing radiation on the testes as decreasing of testicular, epididymal, and seminal vesicle masses; tubular atrophy; reduction of cellular proliferation; and loss of germ cells. LOS was able to prevent some of those deleterious effects, promoting improvements in seminal vesicle mass, sperm vitality, plasma testosterone levels, vacuole number, and cell proliferation. In conclusion, inhibition of the AngII/AT1R axis by LOS is effective in protecting the indirect/delayed radiation damage resulting from oxidative stress established in the tissue.

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Section: Discussionsupporting

confidence: 72%

Losartan Attenuates Radiation-Induced Damage on Testes and Accelerates Tubular Regeneration

Santos

Alves

Chies

et al. 2022

Front. Reprod. Health

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“… 47 , 48 Normal DNA integrity of spermatozoa with valsartan was determined that it might be due to the drug’s antioxidant, anti-inflammatory, and antiapoptotic properties. 49 Similarly, pramipexole showed the normal DNA integrity of spermatozoa, which is attributed to the intracellular presence of dopamine receptors in spermatozoa and antioxidant and anti-inflammatory properties of pramipexole. 50 Normally, dopamine acts as a physiological modulator and is involved in sperm cell viability, capacitation, and motility.…”

Section: Discussionmentioning

confidence: 93%

“…In the current study, venlafaxine showed the normal DNA integrity of spermatozoa, which has indicated that the venlafaxine did not cross the blood testis barrier (BTB) to interfere with the germ cell cycle. The venlafaxine is a protein-bound drug, and the BTB does not allow the passage of protein-bound substances. , Normal DNA integrity of spermatozoa with valsartan was determined that it might be due to the drug’s antioxidant, anti-inflammatory, and antiapoptotic properties . Similarly, pramipexole showed the normal DNA integrity of spermatozoa, which is attributed to the intracellular presence of dopamine receptors in spermatozoa and antioxidant and anti-inflammatory properties of pramipexole .…”

Section: Discussionmentioning

confidence: 99%

Effect of Venlafaxine, Pramipexole, and Valsartan on Spermatogenesis in Male Rats

et al. 2020

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The study’s aim was to explore the effect of venlafaxine, valsartan, and pramipexole on spermatogenesis. It was hypothesized that these drugs may affect the male fertility because of their long-term use in treatment of depression, hypertension, and Parkinson’s diseases. Male rats were given venlafaxine, valsartan, and pramipexole at low- and high-dose levels orally once daily for 10 weeks. Testosterone (25 mg/kg) was given as a standard via an intramuscular route once weekly. Rats were sacrificed after blood collection by cardiac puncture, and testes were removed. Sperm parameters were examined from spermatozoa of the cauda epididymis, and testes were treated for histopathological analysis. Results showed nonsignificant effect of venlafaxine on the sperm count, whereas a decreased sperm count was noted in all the treatment groups as compared to that of the control except valsartan at a low dose, which significantly ( p < 0.001) raised the sperm count (96.26 ± 2.4) in reference with the control value (49.13 ± 2.3). Treatments had variable effects on total sperm motility and morphological parameters, but valsartan at a low dose showed maximum sperm motility (71.55 ± 0.7) among all. DNA integrity of spermatozoa remained intact in all groups. Luteinizing hormone and follicle-stimulating hormone levels decreased, and testosterone levels increased in all treatment groups as compared to control values, which indicate fertility. Histopathology revealed normal texture of testes with venlafaxine and valsartan, but testicular damage occurred with high-dose pramipexole. It is concluded that the use of venlafaxine, valsartan, and pramipexole at a low dose is devoid of any harmful effect on spermatogenesis, whereas pramipexole at a high dose adversely affect it.

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“…Previous studies have shown that testicular recovery after irradiation depends on the survival of spermatogonial stem cells. Their self‐renewal and ability to differentiate, as well as to repopulate the gonads, are essential to the resumption of the spermatogenesis process (da Silva Mansano et al., 2018; Meistrich, 2013). These findings combined with the present results indicate that chronic exposure to radiation at this level in Fukushima did not affect the spermatogonial stem cells of the spermatogenesis process in raccoons.…”

Section: Discussionmentioning

confidence: 99%

Morphological reproductive characteristics of testes and fertilization capacity of cryopreserved sperm after the Fukushima accident in raccoon (Procyon lotor)

Komatsu

Iwasaki

Murata

et al. 2021

Reprod Domestic Animals

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Since the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, we have established an archive system of livestock and wild animals from the surrounding ex‐evacuation zone. Wildlife within the alert zone have been exposed to low‐dose‐rate (LDR) radiation for a long continuous time. In this study, we analysed the morphological characteristics of the testes and in vitro fertilization (IVF) capacity of cryopreserved sperm of racoons from the ex‐evacuation zone of the FDNPP accident. The radioactivity of caesium‐137 (137Cs) was measured by gamma‐ray spectrometry, and the measured radioactivity concentration was 300–6,630 Bq/kg in the Fukushima raccoons. Notably, normal spermatogenesis was observed in the seminiferous tubules of the testes, with the germinal epithelium composed of a spermatogenic cell lineage with no evident ultrastructural alterations; freeze‐thawing sperm penetration ability was confirmed using the interspecific zona pellucida‐free mouse oocytes IVF assays. This study revealed that the chronic and LDR radiation exposure associated with the FDNPP accident had no adverse effect on the reproductive characteristics and functions of male raccoons.

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Effects of telmisartan and losartan on irradiated testes

Cited by 13 publications

References 22 publications

Losartan Attenuates Radiation-Induced Damage on Testes and Accelerates Tubular Regeneration

Losartan Attenuates Radiation-Induced Damage on Testes and Accelerates Tubular Regeneration

Effect of Venlafaxine, Pramipexole, and Valsartan on Spermatogenesis in Male Rats

Morphological reproductive characteristics of testes and fertilization capacity of cryopreserved sperm after the Fukushima accident in raccoon (Procyon lotor)

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