Carbamazepine damage to rat spermatogenesis in different sexual developmental phases

Oliva, Samara Urban de; Miraglia, Stefania

doi:10.1111/j.1365-2605.2008.00898.x

Cited by 29 publications

(34 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These data are in accordance with our previous study [12]; in this former study, a decrease in testosterone plasma levels and an increase in the estrogen level were respectively observed in 63 and 93 day-old rats which were also CBZ-treated from the weaning. In addition, the decrease in the weight of androgen-dependent organs as the ventral prostate is consistent with the decrease in serum levels of testosterone [13,49].…”

Section: Discussionsupporting

confidence: 93%

“…), corresponds to the usual anticonvulsive dose in humans which is effective in preventing kindled seizure in Wistar rats [25,26]. The treatment lasted 20, 40 and 70 days, according to the different stages of the rats' sexual maturation, i.e., adolescence (around 43 days; [12,27]), puberty (63 days; [28,29]) and young adult phase (93 days; [30]). Control animals received only propylene glycol (vehicle of CBZ).…”

Section: Methodsmentioning

confidence: 99%

“…Thus, endocrine changes due to long-term CBZ-treatments may cause a negative impact on pubertal development and fertility both in boys and young men [11]. Damage on the seminiferous epithelium, testicular interstitial oedema, reductions of testosterone levels and increase of estradiol levels were also observed in rats treated with CBZ since weaning [12]. …”

Section: Introductionmentioning

confidence: 99%

“…In addition, as the chronic administration of CBZ is a common schedule utilized for treatment of children and adolescents [11] and can provoke hormonal alterations as well as damage on fertility [8-12]. In addition, given that there are not studies investigating the extension of the prostatic damage, caused by CBZ chronic administration, during the sexual maturation, we assumed that this theme is an essential subject to be investigated.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, given that there are not studies investigating the extension of the prostatic damage, caused by CBZ chronic administration, during the sexual maturation, we assumed that this theme is an essential subject to be investigated. Thus, considering that the maturation of the hypothalamic-pituitary-gonadal (HPG) axis in pre-puberty and puberty is more susceptible to a cytotoxic agent [12,23,24] and also, taking into account that recently we observed estrogen and testosterone level alterations in CBZ-treated rats from the weaning [12], we proposed to evaluate the side effects of CBZ on the ventral prostate of rats in different phases of sexual development; for this goal, the CBZ was administered to rats from the pre-puberty until the adulthood and the histopathological, morphometric and stereological analyses of their prostate ventral lobe were carried out.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Harmful effects of carbamazepine on the postnatal development of the rat ventral prostate

Oliva

Scarano

Okada

et al. 2012

Reprod Biol Endocrinol

View full text Add to dashboard Cite

BackgroundCarbamazepine (CBZ) is a first-line antiepileptic drug (AED), although it is also used for the treatments of psychiatric disorders and neuropathic pain. The CBZ utilization has been associated with male reproductive damage, including hormonal alterations, sexual dysfunction and reduction of sperm quality. The wide and long-term use of the CBZ is a common schedule in children and adolescents and alters the testosterone level in adult rats and humans. The objective of this work was to evaluate the CBZ side effects on the ventral prostate of rats from pre-puberty to sexual maturation, since the prostate is an androgen-dependent organ.MethodsTwenty three day-old male albino Wistar rats received CBZ diluted in propylene glycol (20 mg/Kg/i.p via). The treatment lasted 20, 40 and 70 days, according to the different stages of the rat sexual maturation. At the end of each treatment period, ventral prostates were removed and histologically processed. The prostate sections were submitted to the histopathological, morphological and stereological analyses using image analysis system.ResultsReductions of the glandular epithelium, glandular lumen and fibromuscular stroma volume of the ventral prostate were observed in adult rats treated with CBZ since the weaning. Triggering and degranulation of mast cells were observed in the fibromuscular stroma of prepubertal and pubertal CBZ treated rats.ConclusionsThe results suggest a direct effect of the CBZ on rat ventral prostate, evidenced by increase of mast cell and macrophage populations during pre-puberty and puberty causing a ventral prostate accentuated damage in the adult phase.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Harmful effects of carbamazepine on the postnatal development of the rat ventral prostate

Oliva

Scarano

Okada

et al. 2012

Reprod Biol Endocrinol

View full text Add to dashboard Cite

show abstract

Gonocyte development in rats: proliferation, distribution and death revisited

Zogbi

Tesser

Encinas

et al. 2012

Histochem Cell Biol

View full text Add to dashboard Cite

Spermatogonial stem cells are responsible for the constant production of spermatozoa. These cells differentiate from the gonocytes, but little is known about these cells and their differentiation into spermatogonia. This study analyzed rat gonocyte proliferation, death and distribution as well as their differentiation into spermatogonia. Rat testes were collected at 19 dpc and at 1, 3, 5, 8, 11 and 15 dpp and submitted to apoptosis investigation through morphological analysis and TUNEL, p53 and cleaved caspase 3 labeling. Ki67 and MVH labeling was used to check gonocyte proliferation and quantification, respectively. OCT4 and DBA labeling were used to check gonocyte differentiation. Seminiferous cord length and gonocyte numerical density were measured to check gonocyte distribution along the seminiferous cords. Although a reduction of gonocyte number per testicular section has been observed from 1 to 5 dpp, the total number of these cells did not change. Apoptotic gonocytes were not detected at these ages, suggesting that the reduction in gonocyte number per testicular section was due to their redistribution along the seminiferous cords, which showed continuous growth from 19 dpc to 5 dpp. The first proliferating germ cells were observed at 8 dpp, coinciding with OCT4 upregulation and with the emergence of the first spermatogonia. In conclusion, this study suggests that (a) gonocytes do not die in the first week after birth, but are rather redistributed along the seminiferous cords just before their differentiation into spermatogonia; (b) mitosis resumption and the emergence of the first spermatogonia are coincident with OCT4 upregulation.

show abstract

Testicular toxicity and sperm quality following copper exposure in Wistar albino rats: ameliorative potentials of L-carnitine

Khushboo

Murthy

Devi

et al. 2017

Environ Sci Pollut Res

View full text Add to dashboard Cite

Copper is a persistent toxic and bio-accumulative heavy metal of global concern. Continuous exposure of copper compounds of different origin is the most common form of copper poisoning and in turn adversely altering testis morphology and function and affecting sperm quality. L-carnitine has a vital role in the spermatogenesis, physiology of sperm, sperm production and quality. This study was designed to examine whether the detrimental effects of long-term copper consumption on sperm quality and testis function of Wistar albino rat could be prevented by L-carnitine therapy. The parameters included were sperm quality (concentration, viability, motility, and morphology), histopathology, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum urea, serum creatinine, serum testosterone and testis antioxidant enzyme levels (superoxide dismutase and glutathione-S-transferase), and biomarkers of oxidative stress (lipid peroxidation and expression of heat shock protein 70 in testis). Three-month-old male Wistar rats (n = 30) were divided into six groups as group 1 (G1, 0.9% saline control), group 2 (G2, CuSO4 200 mg/kg dissolved in 0.9% saline water), groups 3 and 4 (G3 and G4, L-carnitine 50 and 100 mg/kg dissolved in 0.9% saline water, respectively), and groups 5 and 6 (G5 and G6, CuSO 200 mg/kg plus L-carnitine, 50 and 100 mg/kg dissolved in 0.9% saline water, respectively). Doses of copper (200 mg/kg) and L-carnitine (50 and 100 mg/kg) alone and in combinations along with untreated control were administered orally for 30 days. The following morphological, physiological, and biochemical alterations were observed due to chronic exposure of copper (200 mg/kg) to rats in comparison with the untreated control: (1) generation of oxidative stress through rise in testis lipid peroxidation (12.21 vs 3.5 nmol MDA equivalents/mg protein) and upregulation of heat shock protein (overexpression of HSP70 in testis), (2) liver and kidney dysfunction [elevation in serum ALT (81.65 vs 48.08 IU/L), AST (156.82 vs 88.25 IU/L), ALP (230.54 vs 148.16 IU/L), urea (12.65 vs 7.45 mmol/L), and creatinine (80.61 vs 48.25 μmol/L) levels], (3) significant decrease in body (99.64 vs 106.09 g) and organ weights (liver-3.48 vs 4.99 g; kidney-429.29 vs 474.78 mg; testes-0.58 vs 0.96 g), (4) imbalance in hormonal and antioxidant enzyme concentrations [significant decline in serum testosterone (0.778 vs 3.226 ng/mL), superoxide dismutase (3.07 vs 8.55 μmol/mg protein), and glutathione-S-transferase (59.28 vs 115.58 nmol/mg protein) levels], (5) severe alterations in the testis histomorphology [sloughed cells (90.65%, score 4 vs 15.65%, score 1), vacuolization (85.95%, score 4 vs 11.45%, score 1), cellular debris along with degenerative characteristics, accentuated germ cell depletion in the seminiferous epithelium, severe damage of spermatogonia and Sertoli cells (73.56%, score 3 vs 0%, score 1)], (6) suppression of spermatogenic process [hypospermatogenesis (low Jhonsen testicular biopsy score 4 vs 9.5), decrease in tubules...

show abstract

Carbamazepine damage to rat spermatogenesis in different sexual developmental phases

Cited by 29 publications

References 53 publications

Harmful effects of carbamazepine on the postnatal development of the rat ventral prostate

Harmful effects of carbamazepine on the postnatal development of the rat ventral prostate

Gonocyte development in rats: proliferation, distribution and death revisited

Testicular toxicity and sperm quality following copper exposure in Wistar albino rats: ameliorative potentials of L-carnitine

Contact Info

Product

Resources

About