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Effects of different doses of curcumin on testicular histopathology, apoptosis, and reproductive organs weight index in mice d-galactose-induced aging model

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Mahdieh Yousefi Taba
Mahdieh Yousefi Taba
Mahdieh Yousefi Taba
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Shabnam Mohammadi
Shabnam Mohammadi
Shabnam Mohammadi
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Mehdi Jalali
Mehdi Jalali
Mehdi Jalali
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Farimah Beheshti at Torbat Heydariyeh University of Medical Sciences
Farimah Beheshti
  • Torbat Heydariyeh University of Medical Sciences
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Due to the value of aging and its effect on body organs, it is necessary to study the factors that can have protective effects on this process. Curcumin is the active ingredient of Curcuma longa Turmeric, which has a strong antioxidant effect. We evaluated the curcumin treatment on testicular histopathology, apoptosis, and reproductive organs index in a mouse model of aging. Forty-eight mice divided into control, sham, d-galactose, and curcumin 1 to 3 groups. The d-galactose group was administered intraperitoneally 300 mg/kg d-galactose for 6 weeks. The curcumin 1 to 3 groups received d-galactose plus 25, 50, and 100 mg/kg of curcumin, respectively for 14 days. Then, testicular histopathology, apoptosis, and reproductive organs index were investigated after 6 weeks. The SPSS software was used for data analysis. Tunnel-positive cells in the d-galactose group were remarkably higher than the control group (p < 0.05). Administration of curcumin in all three doses reduced the number of positive tunnel cells, in comparison with the group that received d-galactose (p < 0.05). The epididymis weight index of the d-galactose group was significantly different from the control (p = 0.006), the sham (p = 0.01), the curcumin 1 (p = 0.003), the curcumin 2 (p = 0.003), and the curcumin 3 (p = 0.002) groups. Histological examination of the d-galactose group revealed a reduction in the thickness of the germinal epithelium, edema, and complete atrophy of germ cells in some seminiferous tubules. The histology of seminiferous tubules was near-normal appearance with the little disintegration of germ cells from their normal germinal epithelium in the curcumin 1 and 3 groups. The histology of seminiferous tubules was near-normal appearance with mild edema and congestion in some seminiferous tubules in the curcumin 2 group. Curcumin supplementation (2 weeks, 100 mg/kg) caused an improvement in biochemical markers and sperm parameters as well as a reduction in apoptosis in the testicular tissue of the aging mouse model.
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ORIGINAL ARTICLE
Effects of different doses of curcumin on testicular histopathology,
apoptosis, and reproductive organs weight index in mice
D-galactose-induced aging model
Mahdieh Yousefi Taba
1
&Shabnam Mohammadi
2
&Mehdi Jalali
1
&Farimah Beheshti
3
&Seyedeh Saleheh Attari
1
Received: 1 November 2018 / Accepted: 19 November 2018 /Published online: 23 November 2018
#Springer-Verlag London Ltd., part of Springer Nature 2018
Abstract
Due to the value of aging and its effect on body organs, it is necessary to study the factors that can have protective effects on this
process. Curcumin is the active ingredient of Curcuma longa Turmeric, which has a strong antioxidant effect. We evaluated the
curcumin treatment on testicular histopathology, apoptosis, and reproductive organs index in a mouse model of aging. Forty-eight
mice divided into control, sham, D-galactose, and curcumin 1 to 3 groups. The D-galactose group was administered intraperito-
neally 300 mg/kg D-galactose for 6 weeks. The curcumin 1 to 3 groups received D-galactose plus 25, 50, and 100 mg/kg of
curcumin, respectively for 14 days. Then, testicular histopathology, apoptosis, and reproductive organs index were investigated
after 6 weeks. The SPSS software was used for data analysis. Tunnel-positive cells in the D-galactose group were remarkably
higher than the control group (p< 0.05). Administration of curcumin in all three doses reduced the number of positive tunnel cells,
in comparison with the group that received D-galactose (p< 0.05). The epididymis weight index of the D-galactose group was
significantly different from the control (p=0.006),thesham(p= 0.01), thecurcumin 1 (p= 0.003), the curcumin 2 (p= 0.003), and
thecurcumin3(p= 0.002) groups. Histological examination of the D-galactose group revealed a reduction in the thickness of the
germinal epithelium, edema, and complete atrophy of germ cells in some seminiferous tubules. The histology of seminiferous
tubules was near-normal appearance with the little disintegration of germ cells from their normal germinal epithelium in the
curcumin 1 and 3 groups. The histology of seminiferous tubules was near-normal appearance with mild edema and congestion in
some seminiferous tubules in the curcumin 2 group. Curcumin supplementation (2 weeks, 100 mg/kg) caused an improvement in
biochemical markers and sperm parameters as well as a reduction in apoptosis in the testicular tissue of the aging mouse model.
Keywords Curcumin .Mice .Aging .Testi s .D-galactose
Introduction
The aging process is a biological phenomenon, which gradu-
ally reduces the efficiency of many physiological functions of
the body and the body’s homeostasis, and leads to the accu-
mulation of damaging materials in the cell as well. With in-
creasing age, testosterone secretion as well as the body’san-
tioxidant defense system decreases along with increases in
apoptosis and free radicals (Momtaz and Abdollahi 2012;
Attari et al. 2018). The aging phenomenon affects various
body organs, including the nervous system and the urogenital
system. Various factors, such as environmental conditions and
nutrition, have a significant impact on the process. There are
more than 300 theories on the aging process, many of which
overlap. One of the most prominent of these is the theory of
free radicals. According to this theory, the antioxidant defense
system cannot neutralize all the free radicals generated during
*Shabnam Mohammadi
Mohammadish@mums.ac.ir
Mahdieh Yousefi Taba
YousefiTM941@mums.ac.ir
Mehdi Jalali
JalalM@mums.ac.ir
Farimah Beheshti
BeheshtiF931@mums.ac.ir
Seyedeh Saleheh Attari
AttariS1@mums.ac.ir
1
Department of Anatomy and Cell Biology, School of Medicine,
Mashhad University of Medical Sciences, Mashhad, Iran
2
Neurogenic Inflammation Research Center, Mashhad University of
Medical Sciences, Mashhad, Iran
3
Department of Physiology, School of Medicine, Mashhad University
of Medical Sciences, Mashhad, Iran
Comparative Clinical Pathology (2019) 28:997–1002
https://doi.org/10.1007/s00580-018-2870-7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Aging is a biological phenomenon that causes various disorders and diseases in body systems such as the nervous, cardiovascular, and reproductive systems (1,2). Lifestyle changes, modernization, and increased life expectancy have led to an increase in the age of marriage in developed and developing countries (3). The most prominent theory in relation to the aging process is the free radical theory, which states that the production of free radicals can lead to tissue and cellular oxidative damage and ultimately lead to aging and cell death. ...
... The most prominent theory in relation to the aging process is the free radical theory, which states that the production of free radicals can lead to tissue and cellular oxidative damage and ultimately lead to aging and cell death. The anti-oxidant system cannot neutralize all free radicals produced during a lifetime therefore; oxidative stress causes various diseases and dysfunctions of the body systems (3,4). ...
... D-gal-induced animals have shown aging-related changes in body physiology and phenotypes such as neurological deficit, decreased immune responses, activity of anti-oxidant enzymes, and increased ROS production and reproductive toxicity. According to the results of different studies, aging leads to degenerative changes in reproductive tissues along with a decrease in sperm quality and most matings do not lead to success in fertility (1,3,9). ...
Impact of caffeic acid on the testicular damages in D-galactose-induced aging model in mice
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  • Oct 2022
Objectives: Aging is a biological phenomenon that causes various disorders and diseases in body systems such as the reproductive system. One of the important factors in aging is oxidative stress, which facilitates the aging process through various mechanisms. The aim of this study is the investigation of effects of caffeic acid on the testicular damages in Dgalactose induced aging model in mice. Materials and methods: Forty male mice were randomly divided into 5 groups (n=8): 1) Control, 2) Sham, 3) Aging, 4) Aging + caffeic acid, and 5) Caffeic acid. Aging was induced through daily injection of D-Galactose (300 mg/kg, intraperitoneal) for 6 weeks. Caffeic acid (60 mg/kg, intraperitoneal) was injected daily for 6 weeks. One day after the last injection mice were killed and the testicle and epididymis were removed. Then, sperm parameters, factors of oxidative stress, and histopathological changes were evaluated. Results: The results showed that aging significantly decreased the count, motility, and viability of sperm, and increased abnormal sperm and sperm DNA fragmentation in contrast to the control group (P<0.05). In addition, MDA levels increased significantly in this group, and SOD, GPx, and TAC activity decreased (P<0.05). Histological studies also showed the destruction of seminiferous tubules, and Johnson's score decreased (P<0.05). Caffeic acid administration significantly improved the above disarrays (P<0.05). Conclusion: The results showed that caffeic acid reduces the adverse effects of aging on spermatogenesis in mice by reducing oxidative stress and increasing antioxidant defenses.
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... Curcumin has been shown to also have a positive effect on testicular morphology and morphometry. This is based on research by Taba et al. (2019), supplementation with curcumin can improve testicular structure and weight. This mechanism occurs with the effect of curcumin which can protect the testicles from oxidative stress damage. ...
Antifertility Effects of Curcumin on Sperm Quality, Morphology of Testicular, and Seminal Vesicle in Rats (Rattus norvegicus)
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Several studies report that curcumin has antifertility effects and has the potential to regulate male fertility (contraception). However, determining the initial dose is preliminary studies based on spermatozoa quality parameters, morphology, and morphometry of testes and seminal vesicles that have never been reported. The main objective of this research is to examine the effects of curcumin on several aspects of reproduction and determine the optimal dose for using curcumin as an antifertility agent. The test animals in this study were Wistar rats (Rattus norvegicus) three-month-old males weighing 300 g. Rats were acclimatized for 7 days and given standard feed and water ad libitum. During the research, rats were given standard 552SP feed. A total of six rats were used in this study, then divided into two treatment groups, namely C1 (given standard feed and distilled water orally (without curcumin)); and C2 (given standard feed and oral curcumin 150 mg /kg body weight). The length of treatment followed the duration (cycle) of spermatogenesis in rats, namely 52 days. Data were analysed using the T-test independent. The results indicate a rise in variables related to spermatozoa abnormality and a reduction in spermatozoa concentration, showing no statistically significant differences (P>0.05). Similarly, there were no significant variations (P>0.05) observed in all variables related to testis and seminal vesicle morphology. The administration of curcumin did not yield a statistically significant effect (P>0.05) on decreasing spermatozoa quality concerning testicular morphology, morphometry, and seminal vesicle weight. However, a trend was observed indicating an increase in spermatozoa abnormalities and a decrease in spermatozoa concentration.
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... This increase in testicular weight was owed to the cessation of excessive apoptosis of cells in testes with administration of curcumin. It was proven that curcumin supplementation (2 weeks, 100 mg/kgBW) reduced apoptosis in testicular tissues of old mice [31]. ...
Curcumin Protective Potential for the Seminiferous Tubules of Mice Treated with Lead Acetate
Article
Full-text available
  • Jul 2023
Curcumin as an antioxidant plays an important role in reducing lead toxicity. This research aimed to demonstrate the potential of curcumin in maintaining epithelial thickness and diameter of seminiferous tubules of mice treated with lead acetate. Thirty BALB/c mice (Mus musculus) were divided into 5 groups. Group N was the negative control group with no treatment. Group P was the positive control group, which was given 0.075 g/kgBW of lead acetate once in a day for 35 days. The treatment groups, T1, T2 and T3, were treated with curcumin 100, 200 and 400 mg/kg BW once a day for 3 days; after 3 days, they were treated with curcumin 100, 200 and 400 mg/kg BW; then, 1 h later, they were treated with lead acetate 0.075 g/kg BW once a day for 35 days. There was a significant difference in epithelial thickness of seminiferous tubule between group P and group T3, and a significant difference in the diameter of seminiferous tubules between group P and groups T2 and T3. Curcumin dosages of 200 and 400 mg/kgBW could significantly maintain the diameter of seminiferous tubules, and curcumin dosage of 400 mg/kgBW could significantly maintain the epithelial thickness of seminiferous tubules of mice treated with lead acetate. HIGHLIGHTS Curcumin as an antioxidant plays an important role in reducing lead toxicity Administration of curcumin could increase the diameter and epithelial thickness of seminiferous tubules, as well as the testicular weight. It was proven that curcumin reduced apoptosis activity by, among others, chelating with lead and serving as a ROS (reactive oxygen species) scavenger Our research found the best dosages of curcumin that could significantly maintain the diameter and epithelial thickness of seminiferous tubules of mice treated with lead acetate GRAPHICAL ABSTRACT
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... Dgal exposure has also caused various testicular histopathological impairments in this study.The results suggested that D-gal exerted toxic effects on rat testis through increased oxidative stress, causing various testicular structural damages. Earlier studies have also shown various structural alterations such as damaged seminiferous tubules, decreased epithelium layers, and decreased spermatogenic cells in histopathological investigations of mice exposed to D-gal(37). Changes in male reproductive systems caused by D-gal, such as testicular damage, decreased sperm count, and reduced androgen production with increased serum LH and FSH, are similar to normal aging(2). Based on the present findings, it can be concluded that D-gal exposure caused several alterations in the male reproductive system via increased production of ROS, enhanced inflammation cascade, and reduced androgen production. ...
Testosterone propionate and Swarna Bhasma treatment modulated D-galactose induced reproductive alterations in male Wistar rats: An experimental study
Article
Full-text available
  • May 2023
Background: The male reproductive system undergoes several adverse age-related changes like decreased hormone synthesis, sperm count, and testicular alteration that can impact on fertility. Objective: The study aims to investigate the effects of testosterone propionate (TP), and ayurvedic formulation Swarna Bhasma (SB) on D-galactose (D-gal) induced reproductive aging in male Wistar rats. Materials and methods: 60 male Wistar rats were divided into 10 groups of 6 animals. Reproductive aging was induced by D-gal (150 mg/kg Bwt) exposure for 60 days. The rats were then treated by post and combination treatment with TP (2 mg/kg Bwt) and SB (6.75 mg/kg Bwt). Then sperm parameters, reproductive hormones, inflammatory markers, testicular antioxidant enzymes, steroidogenic enzymes, and histological manifestation of testis were evaluated. Results: Exposure of D-gal caused significant (p < 0.001) decrease in serum testosterone (T), testicular steroidogenic, and antioxidant enzymes. Administration of TP increased the serum T level, testicular antioxidant enzymes, and spermatogenic profile at a significant level of (p < 0.001) compared to D-gal. Further, the SB treatment significantly (p < 0.001) elevated the serum T level, sperm count, testicular antioxidant enzymes, steroidogenic enzymes, when compared to D-gal. Conclusion: Both the treatment of TP and SB treatments recovered the reproductive impairments caused by D-gal. However, exogenous T supplementation via TP administration is associated with various side effects during long-term use. SB is an Ayurvedic formulation having a long history of usage in India. The current findings suggest that the SB may be used as a good alternative for potentiating reproductive function in aging males.
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... The anti-apoptotic action may involve regulation of pro-and anti-apoptotic proteins, the release of mitochondrial cytochrome c and activation of caspase-dependent cell death pathways. Taba et al. [104] showed that CUR administration causes a reduction in tunnel positive apoptotic cells as well as an alleviation in biochemical markers and sperm parameters in the testicular tissue of the aging mouse model. Furthermore, the investigation of Zalok et al. [105] showed that co-administration of CHI nanoparticles with cimetidine resulted in the weak immune response against caspase 3 in the seminiferous tubules of mouse testicular tissues. ...
Efficiency of Curcumin and Chitosan Nanoparticles Against Toxicity of Potassium Dichromate in Male Mice
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Objective: The purpose of this work is to examine the protective effect of nanocurcumin and nanochitosan supplementation against potassium dichromate toxicity in male mice. Methods: Male albino mice weighing 25-30 gm were divided into six groups; the first group received saline. Second and third groups were given oral dose of nanocurcumin and nanochitosan respectively for 5 d. Fourth group was injected subcutaneously with a single dose of potassium dichromate for 24 h. Group five and six were administrated nanocurcumin and nanochitosan, respectively prior to potassium dichromate. Animals were anesthetized by ether anesthesia then bone marrow was harvested for chromosomal examination and epididymal sperms were collected for sperm morphology, while Kidneys and testes were collected for western blot and biochemical analysis. Results: Potassium dichromate induced significant (P≤0.05) increase in chromosome and sperm abnormalities as well as testicular and renal MDA, renal MPO, renal contents of IL-18 and IGF-1, testicular contents of caspase 3 and cytosolic cytochrome c, a reduction in testosterone level, and GPx of renal and testicular tissues compared to control group. Pretreatment with both types of nanoparticles showed significant (P≤0.05) mitigation against most alterations induced by potassium dichromate; moreover, nanochitosan gave more significant (P≤0.05) improvement against chromosome and sperm abnormalities than nanocurcumin. Conclusion: The present study revealed that the selected nanoparticles have antioxidant as well as antigenotoxic properties against toxicity of potassium dichromate.
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... By studying the effects of different doses of curcumin 25, 50, and 100 mg/kg during 14 days on reproductive organ weight index, testicular histopathology and apoptosis in a mouse aging model. Taba et al., (2019) 40 indicated that Curcumin supplementation (2 weeks, 100 mg / kg) induced improvement in biochemical markers and sperm parameters as well as reduction of apoptosis in testicular tissue. ...
Effect of Curcuma longa Aqueous Extract on Male Fertility in Aluminum Exposed Wistar Rats
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Full-text available
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To assess the effects of Curcuma longa aqueous extract (CE) on fertility in male rats exposed to Aluminum chloride (AlCl3), Twenty four male rats, 3 months old, divided into 4 groups (n=6) were used. Animal from the first group received, by the oral route, water-containing AlCl3 at the dose of 34 mg/kg body weight (BW). Rats from the second group received both AlCl3 at the same dose in combination with oral treatment of CE at a dose of 200 mg/kg BW. The third group received only an oral administration of CE with the same dose. Rats from the fourth group, without any treatment, served as control. After 4 weeks of experimentation, AlCl3 exposure showed a significant decrease in sperm concentration (4.58±0.65 × 106 cells /ml), and percentage of viability (61.53±23.63 %), and an increase of morphological abnormalities (26.11±17.84 %). A significant decreased in serum testosterone levels (0.31±0.26 ng/ml) and an increase of testicular malondialdehyde (MDA) level (0.16±0.015 μM/g) were also observed. Histological examination of the testes showed degeneration of the seminiferous tubules, germ line cells, and interstitial cells. However, CE treatment concomitant to AlCl3 showed that the rate of morphological abnormalities (19±2.65 %) is significantly decreased compared to the AlCl3 group, with a significant increase in serum testosterone (1.17±0.24 ng/ml) and a significant decrease in MDA (0.11±0.003μM/g) level. Microscopic examination revealed a significant regeneration of seminiferous tubules and interstitial cells. This study demonstrated an ameliorative effect of Curcuma longa aqueous extract in testicular tissue and sperm quality.
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... The length of the colon and the organ index of the liver, spleen and kidney were calculated. The following formula was used to calculate the organ index (35): Organ index (%)=mean organ weight/mean body weight x100. ...
Protective effect of Gloeostereum�incarnatum on ulcerative colitis via modulation of Nrf2/NF‑κB signaling in C57BL/6 mice
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Chronic non‑specific inflammatory cell infiltration of the colon is generally considered to be the cause of ulcerative colitis (UC). Gloeostereum incarnatum (GI), a fungus rich in amino acids and fatty acids, exhibits a variety of biological functions. In the present study, GI was identified to contain 15 fatty acids, 17 amino acids and 11 metallic elements. The protective effect of GI against UC was investigated in C57BL/6 mice with UC induced by free drinking 3.5% dextran sulfate sodium (DSS). After a 21‑day oral administration, GI prevented weight loss, enhancement of the disease activity index and colonic pathological alterations in mice with UC. GI reduced the levels of pro‑inflammatory factors including interleukin (IL)‑1β, IL‑2, IL‑6 and IL‑12, tumor necrosis factor α and ‑β, interferon α and ‑γ, and pro‑oxidative factors including reactive oxygen species and nitric oxide. In addition, it enhanced the levels of immunological factors including immunoglobulin (Ig)A, IgM and IgG, and antioxidative factors including superoxide dismutase and catalase in the serum and/or colon tissues. GI enhanced the expression levels of nuclear factor erythroid 2‑related factor 2 (Nrf2) and its downstream proteins and suppressed the phosphorylation of NF‑κB signaling in colon tissues. Together, GI was shown to alleviate the physiological and pathological state of DSS‑induced UC in mice via its antioxidant and anti‑inflammatory functions, which may be associated with its modulation of the activation of Nrf2/NF‑κB signaling.
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... It was previously hypothesized that male gonad seems to fully escape the toxic effects galactose exerts on the ovary (Forges et al. 2006) given that there was no gonadal toxicity in male offspring of galactose-fed rats (Chen et al. 1984). Recent studies reveal that D-galactose (Dgal) has been widely used to induce aging of rodents with consequential effects on hepatocytes (Gao et al. 2018;Saleh et al. 2019) and testicular cells (Aydin et al. 2018;Taba et al. 2018), although it is not known whether modulation of the mPT pore is involved. The reported toxic effects of galactose to hepatocytes and testicular cells include induction of oxidative damage, alterations in antioxidant defense and in addition, sperm cells respond by reduction in count, motility and percentage of morphologically normal sperm. ...
Comparative effects of galactose -induced aging on mitochondrial permeability transition in rat liver and testis
Article
  • Apr 2020
This study investigated the status and sensitivity of mitochondrial permeability transition (mPT) pore in testis and liver of rats exposed to doses of galactose, an acceptable model used to mimic natural aging . Male albino rats were divided into five groups of eight (8) animals in each group for in vivo studies and administered distilled water, 50,100, 200 mg and 500 mg galactose/kgbdwt, respectively, for six (6) consecutive weeks. Mitochondria were isolated from liver and testis by differential centrifugation. Mitochondrial permeability transition (mPT) was assessed as mitochondrial swelling and was monitored spectrophotometrically. Mitochondrial lipid peroxidation, ATPase activity, antioxidant enzymes, caspase activation, interleukins and sperm functional characteristics were also assessed. Administration of galactose (50-500mg/kg) to male Wistar albino rats had no effect whatsoever on the testicular mPT pore. However, liver mPT pore was significantly opened. Furthermore, enhancement of mitochondrial ATPase activity and malondialdehyde generation were observed in the liver of galactose-exposed rats. Significant alterations in antioxidant enzymes were observed in Post Mitochondrial Fraction (PMF) of liver and testis. There were also increases in serum levels of IL-1β and 6. In addition, caspases 9 and 3 were significantly elevated in PMF of the liver with evidence of DNA fragmentation. However, there was no significant difference in levels of caspases in PMF of testis in model groups of galactose when compared with control. These results provide evidence that testis mitochondria do not readily undergo permeability transition pore upon exposure to doses of D-galactose that induce the opening of the pore in the liver. • Highlights • Testicular mitochondria are less sensitive to induction of permeability transition than liver mitochondria in rats exposed to D-galactose for 6 weeks, despite the occurrence of alterations in the antioxidant defense system and generation of ROS in sperm cells as in hepatocytes. • The occurrence of mitochondrial permeability transition in liver of galactose-exposed rats is consistent with malondialdehyde production, alteration in antioxidant levels, enhanced ATPase activity, caspases-9 and 3 activation, immune dysfunction, and DNA fragmentation. • The study of biochemical basis of reduced sensitivity of testis to permeability transition under conditions which the liver is extremely susceptible may become useful in age associated-neurodegenerative diseases where apoptosis is upregulated and has to be properly managed to achieve downregulation.
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Effects of Thymoquinone on Sperm Parameters, Apoptosis, Testosterone Level, and Oxidative Stress in a Mouse Model of D-Galactose-Induced Aging
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Full-text available
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Background: The aging process is accompanied by low secretion of sex hormones and testicular apoptosis. The antioxidant properties of thymoquinone (TQ) may prevent the effects of aging. Therefore, in the present study, the effects of different doses of TQ were investigated on sperm parameters, testosterone level, apoptosis, and oxidative stress in a mouse model of D-galactose-induced aging. Methods: In this experimental study, 30 adult male mice were randomly divided into 5 groups. The control group did not receive any injections, while the D-galactose group received an intraperitoneal injection of 300 mg/kg of D-galactose for 42 days. The TQ1-TQ3 groups received intraperitoneal injections of 5, 2.5, and 1.25 mg/kg of TQ plus Dgalactose, respectively for 14 days (from the 1st to the 14th day of the experiment). The morphometric analysis, testicular apoptosis examination, and sperm analysis were performed, and testosterone level, total antioxidant capacity, and malondialdehyde level were evaluated on day 42 of the experiment. Data were analyzed using SPSS. Results: Administration of TQ in the TQ1 group caused a significant difference in sperm parameters, compared to the D-galactose group (P<0.05). The lowest amount of positive tunnel cells was related to 5 mg/kg of TQ and the highest to 2.5 mg/kg of TQ. There was no significant difference in the parameters of seminal vesicles, epididymis, prostate, and testis between the groups (P>0.05). The malondialdehyde level were decreased in the TQ1-TQ3 groups, compared to the D-galactose group (P<0.001). On the other hand, the total antioxidant capacity was increased significantly in the TQ1 group, compared to the Dgalactose group (P<0.001). Conclusion: Administration of 5 mg of TQ for 14 days improved sperm quality and biochemical parameters, while reducing apoptotic cells of the testes in a mouse model of aging.
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Co-culture of mouse spermatogonial stem cells with sertoli cell as a feeder layer, stimulates the proliferation and spermatogonial stemness profile
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Full-text available
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Objectives: Sertoli cells effect the fate map of spermatogonial stem cells (SSCs) to self-renew via providing the special microenvironments. Maintenance of proliferation and self-renewal activity of SSCs may be usable as a therapeutic strategy, leads to increase the recovery of male fertility. This research was aimed to evaluate the effect of mouse sertoli cells on spermatogonia stem cells proliferation and the expression pattern of stemness markers. Methods: Spermatogonia stem cells were collected from neonatal mouse testis using a two-step mechanical and enzymatic digestion. SSCs were cultured in three groups: The first group or co-culture group consists of spermatogonia and sertoli cells that were cultured together. The control group, only spermatogonial cells and the group no. 3 included spermatogonial cells in the presence of GDNF. The colony formation of mentioned groups, was monitored during one month in culture. Identification of the colonies, was confirmed using PLZF and Oct4 immunostaining. Spermatogonial stemness genes includes; Stra8, mvh and piwill2 were analyzed by RT-PCR. Results: In the co-culture group, cells proliferated rapidly and many colonies were appeared whereas they were rarely formed in the control groups. Colonies were exhibited alkaline phosphatesase activity and were immunopositive to Oct4 and PLZF, strongly. The gene expression of srta8, mvh and piwill2, in SSCs that were cultivated with sertoli cells, were greater significantly than other control groups. Conclusion: It is concluded that co-culture of SSCs with sertoli cells prepares conditions which leads to efficient proliferation and maintenance of stemness condition of SSCs, that is usable as a therapeutic approach for treatment of male fertility.
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Aluminium-Induced Oxidative Stress, Apoptosis and Alterations in Testicular Tissue and Sperm Quality in Wistar Rats: Ameliorative Effects of Curcumin
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  • INT J FERTIL STERIL
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The Effect of Different Doses of N-acetyl Cysteine on Biochemical and Histopathological Parameters in Kidney of Formalin-treated Mice
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Background and Aims: Formaldehyde, a colorless aldehyde with pungent odor, has negative effects on systems of the body. Considering, there are a little data about protective substances against kidney damage induced by formaldehyde, the aim of the present study was to examine the effects of different doses of N-acetyl cysteine on biochemical and histopathological parameters in kidney of mice exposed to formaldehyde. Methods: A total of 48 adult male mice were randomly divided into six groups. Control group did not receive any injection. Formaldehyde group received 10 mg/kg formaldehyde. Third to sixth groups received 10 mg/kg formaldehyde as well as respectivly 50, 100, 200 and 400 mg/kg N-acetyl cysteine, intraperitoneally. After 14 days, slides from kidney were prepared and kidney volume and glomeroules number were obtained by steriologic method. Besides, levels of serum urea and cranitine were measured. Data were analyzed through SPSS software and using ANOVA. Results: Administration of formaldehyde has caused necrosis, cast and vacuolization in kidney tubules. Collapse and sclerosis were observed in the glomeruli. Effects of N-acetylcysteine were dose-dependent; that is, administration of high doses of N-acetylcysteine caused glomerular and tubular damage. In the group received 50 mg/kg N-acetylcysteine, glomeruli and interstitial tissue were normal. The glomerular volume and urea levels in the experimental group 3 and 6 were significantly different compared to the control group (P = 0.000). The number of glomeruli and the level of creatinine in the groups receiving N-acetylcysteine was significantly different compared to the control group (P = 0.000). Conclusion: Administration of 50mg/kg N-acetyl cysteine for 14 days caused protective effect on kidney tissue of mice that had received formaldehyde. Keywords Formaldehyde; Kidney damage; Mouse; N-acetyl cystein
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Full-text available
  • Sep 2016
Introduction: Lead is one the heavy metals that cause negative effects on the body systems. However, there is little data about the effect of antioxidants on kidney damage induced by the lead. Therefore, the aim of the present study was to evaluate the effects of different doses of manganese on biochemical and histopathological parameters of kidney in mice. Materials and Methods: In this study, 48 adult Balb/C male mice were randomly divided into six groups. Control group did not receive any injection. Second group received 60 mg/kg lead acetate intraperitoneally. Third to sixth groups were injected 60 mg/kg lead acetate and 2.5-5-10-20 mg/kg manganese intraperitoneally, respectively. After 14 days, slides from kidney of mice prepared and the volume of kidney and volume and number of glomeruli were measured by stereological method. Besides, levels of serum urea and creatine were measured. Results: Evaluation of the kidney tissue in lead poisoning group showed collapse and glomerulosclerosis as well as tubular vacuolization and necrosis. In the 2.5 mg/kg manganese-treated group less tissue damage occurred. A significant increase in volume of kidney was observed in 2.5, 5 mg/kg manganese-treated and lead poisoning groups (P
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Curcumin ameliorates high‑fat diet‑induced spermatogenesis dysfunction
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  • Sep 2016
Curcumin, a type of natural active ingredient, is derived from rhizoma of Curcuma, which possesses antioxidant, antitumorigenic and anti‑inflammatory activities. The present study aimed to investigate whether treatment with curcumin reduced high‑fat diet (HFD)‑induced spermatogenesis dysfunction. Sprague‑Dawley rats fed a HFD were treated with or without curcumin for 8 weeks. The testis/body weight, histological analysis and serum hormone levels were used to evaluate the effects of curcumin treatment on spermatogenesis dysfunction induced by the HFD. In addition, the expression levels of apoptosis associated proteins, Fas, B‑cell lymphoma (Bcl)‑xl, Bcl‑associated X protein (Bax) and cleaved‑caspase 3, were determined in the testis. The results of the present study suggested that curcumin treatment attenuated decreased testis/body weight and abnormal hormone levels. Morphological changes induced by a HFD were characterized as atrophied seminiferous tubules, decreased spermatogenetic cells and interstitial cells were improved by curcumin treatment. In addition, curcumin treatment reduced apoptosis in the testis, and decreased expression of Fas, Bax and cleaved‑caspase 3, as well as increased expression of Bcl‑xl. In conclusion, the present study revealed that curcumin treatment reduced HFD‑induced spermatogenesis dysfunction in male rats.
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Systematic and comprehensive investigation of the toxicity of curcuminoid‑essential oil complex: A bioavailable turmeric formulation
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Full-text available
  • Nov 2015
Curcumin, the active component present in Curcuma longa of the family Zingiberaceae, has a number of pharmacological effects, including potential anti‑inflammatory activity. One of the major limitations of curcumin/turmeric extract is its poor absorption through the gastrointestinal tract. Several approaches have been adopted to increase the bioavailability of curcumin, including loading curcumin into liposomes or nanoparticles, complexation with phospholipids, addition of essential oils and synthesizing structural analogues of curcumin. In the present study, the toxicity and safety of one such bioavailable turmeric formulation, curcuminoid‑essential oil complex (CEC), the toxicity profile of which has not been reported, were examined using in vivo and in vitro models, as per the guidelines of the Organisation for Economic Co-operation and Development. Investigations of acute toxicity study were performed in rats and mice, and the results revealed no signs and symptoms or toxicity or mortality in any of the animals at the maximum recommended dose level of 5,000 mg/kg body weight. The repeated administration of CEC for 90 days in Wistar rats at a dose of 1,000 mg/kg body weight did not induce any observable toxic effects, compared with corresponding control animals. Mutagenicity/genotoxicity investigations were also performed using a bacterial reverse mutation assay (Ames test), a mammalian bone marrow chromosome aberration test and a mammalian erythrocyte micronucleus test in mice. CEC was found to be non‑mutagenic in all three mutagenic investigations. Consequently, the present study indicated that CEC elicited no toxic effects in animals or in vitro. Therefore, following investigations of acute toxicity, repeated dose toxicity and mutagenicity, CEC was deemed a safe, non‑toxic pharmacological formulation.
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A Comprehensive Review of Biochemical and Molecular Evidences from Animal and Human Studies on the Role of Oxidative Stress in Aging: An Epiphenomenon or the Cause
Article
  • Jan 2012
  • Asian J Anim Vet Adv
Aging is an undeniable fact shadowing animal life but while it comes to human, aging affects all aspects of their physical and emotional abilities. Aging occurs by multi-stimuli which is affected by both environmental and internal conditions. During the past decade, remarkable recognition of cellular senescence and its related pathways has happened. The increased production and/or ineffective scavenging of oxidants in particular, Reactive Oxygen Species (ROS) play a critical role in cellular senescence. High reactivity of ROS determines chemical changes in virtually all cellular components, leading to senescence mostly via DNA damage. Present paper discusses the oxidative stress as the main cause of aging and the benefit of antioxidants. So far, more effective explorations are needed to decrease the deleterious effects of oxidative-stress-induced aging. This approach could be achieved through manipulations of antioxidant enzyme systems, development of drug therapies, manipulation of aging related genes and genetic manipulation of plant-based antioxidant resources.
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