curcumin and Testicular-Diseases

The cancer therapy using cyclophosphamide (CP) has been associated with adverse effects on the testicular function that raises concerns about the future fertility potential among cancer survivors. Curcumin, a polyphenol, has shown to possess a plethora of biological functions including tissue protective effects. In the present study, we investigated the protective effects of curcumin nanocrystals (NC) in mitigation of CP-induced testicular toxicity. Healthy adult (8-10 week) and prepubertal (2 week) male Swiss albino mice were injected with a single dose of CP (200 mg/kg) intraperitoneally (i.p). NC (4 mg/kg, i.p.) was administered every alternate day, for 35 days in adult mice while, a single dose of NC was injected intraperitoneally to prepubertal mice 1 h prior to CP. Administration of multiple doses of NC ameliorated CP-induced testicular toxicity in adult mice, which was evident from the improved sperm functional competence, sperm chromatin condensation, seminiferous tubule architecture and decreased apoptosis in testicular cells. Further, administration of NC 1 h prior to CP in prepubertal mice modulated the expression of genes pertaining to proliferation, pluripotency, DNA damage and DNA repair in spermatogonial cells at 24 h after the treatment. Overall, these results suggest that NC could be a promising chemoprotective agent, which can have potential application in male fertility preservation.

Topics: Animals; Antineoplastic Agents, Alkylating; Antioxidants; Cell Proliferation; Curcumin; Cyclophosphamide; DNA Damage; Drug Compounding; Gene Expression Regulation; Infertility, Male; Male; Mice; Nanoparticles; Oxidative Stress; Spermatogonia; Testicular Diseases; Testis; Time Factors

Cisplatin is a chemotherapeutic drug used to treat testicular cancer that induces testicular toxicity. This study aimed to investigate the possible role of androgens, androgen receptor, and organic cation transporter 2 (OCT2) in the protective effects of curcumin on cisplatininduced testicular toxicity.. Thirty male Wistar rats were divided into five groups: 1- control (normal saline, 0.5 ml ip, daily for 10 consecutive days); 2- cisplatin (10 mg/kg ip, single dose at the first day); 3- cisplatin + curcumin (10 mg/kg ip, dissolved in 5% DMSO, daily for 10 consecutive days); 4- cisplatin + vehicle (DMSO 5%, 0.3 ml ip); and 5- curcumin (10 mg/kg ip). At the end of the study, a blood sample was obtained for testosterone measurement. The left testis was kept at -80. to measure androgen receptor (AR) and type 2 organic cation transporter (OCT2) gene expression and the right testis were kept in 10% formalin for histological analysis.. Cisplatin significantly decreased serum testosterone, declined testis AR gene expression, and increased OCT2 gene expression in testis (p<0.01). Curcumin treatment significantly prevented these alterations in testosterone and gene expressions (p<0.01). Moreover, curcumin significantly reversed the cisplatin-induced kidney tissue injury and increased spermatid and spermatozoa.. It is concluded that the ameliorative effect of curcumin in cisplatin-induced reproductive disorders was due to the modulation of testosterone and androgen receptors.

Topics: Animals; Cisplatin; Curcumin; Disease Models, Animal; Male; Organic Cation Transporter 2; Protective Agents; Rats, Wistar; Receptors, Androgen; Signal Transduction; Testicular Diseases; Testis; Testosterone

This study investigated the effect of ketogenic diet on monosodium glutamate (MSG)-induced testicular dysfunction. Forty-six male rats (180 ± 40 g) were grouped into two groups (23 rats each); control group and MSG-induced group (4 mg/kg bw) for 28 days. At the 29th day, 5 rats from both group were sacrificed to establish testicular dysfunction. The remaining animals from the control group was further divided into three sub-groups and treated for 42 days; untreated group, ketogenic diet only and curcumin only as the standard drug (150 mg/kg bw). In the pre-treatment, the administration of MSG resulted in a significant (p < 0.05) decrease in the testis-body weight ratio, alkaline phosphatase (ALP), acetylcholine esterase (AChE), cholesterol, triglycerides (TG), nitric oxide (NO), glycogen, protein and antioxidant enzymes in the testis. In the post treatment, the MSG only group significantly reduced testicular cholesterol, catalase (CAT) and NO. In contrast, MSG + ketogenic diet group showed a significant increase in levels of rat testicular acid phosphatase (ACP), ALP, cholesterol, HMG-CoA, TG, malondialdehyde (MDA), reduced glutathione (GSH) and NO. The ketogenic diet showed a significant increase (p < 0.05) in the levels of NO, ALP, cholesterol, HMG CoA reductase and (TG). In addition, significant increases in levels of rat testicular ACP, ALP, HMG-CoA, (CAT), SOD and GSH were recorded for MSG + Curcumin group. Taken together, the findings support the prospects of ketogenic diet to enhance the testicular function in rats.

Topics: Animals; Antioxidants; Cholesterol; Curcumin; Diet, Ketogenic; Glutathione; Male; Nitric Oxide; Oxidation-Reduction; Rats; Sodium Glutamate; Superoxide Dismutase; Testicular Diseases; Triglycerides

Testicular damage contributes to cyclosporine A (CsA) induced male infertility. However, the exact underlying molecular mediators involved in CsA-induced testis disorder remains unclear. The present study aimed to characterize the role of mir-34a/sirt-1 in CsA induced testicular injury alone or in combination with curcumin. A total of twenty-eight male Wistar rats were subdivided into four groups: control (Con), sham, cyclosporine A (CsA), cyclosporineA + curcumin (CsA + cur). The animals received cyclosporine A (30 mg/kg) and curcumin (40 mg/kg) for 28 days by oral gavage. At the end of the experiment, CsA administration significantly resulted in a decrease in testis weight and testis coefficient. The molecular analysis demonstrated that CsA exposure increased 8-OHdg and Nox4 protein contents in the testis tissue. TUNEL staining indicated that CsA caused the number of apoptotic cells to increase in the testes of male rats. In addition, exposure to CsA resulted in an increased expression of Bax, and a decreased expresion in that of Bcl-2, with a concomitant up-regulation of the Bax/Bcl-2, c-Caspase-3/p-Caspase-3 ratio and cytochrome c level. Meanwhile, exposure to CsA increased the expression of mir-34a and decreased sirt-1 protein level in the testis tissue samples compared to the control group. Taken together, our findings suggested that CsA can cause damage to testicular germ cells via oxidative stress and mitochondrial apoptotic pathway, and probably mir-34a/sirt-1 play a crucial role in this process. It also demonstrates that these negative effects of CsA can be reduced by using curcumin as an antioxidant and anti-inflammatory agent.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; Curcumin; Cyclosporine; Cytochromes c; Gene Expression; Male; MicroRNAs; Organ Size; Oxidative Stress; Rats, Wistar; Sirtuin 1; Testicular Diseases; Testis

Diabetes affects the reproductive system. This study was conducted to find out the potent dose of the hydro-methanol 60:40 extract of Curcuma amada rhizomes for the management of diabetes-induced testicular dysfunction in albino rats. The extract was administered at the doses of 10, 20, 40, and 80 mg/100 g body weight/day for 28 days. Oxidative stresses, reproductive parameters, histological, and gene expressions of the testicular tissue were assessed. Out of the doses used, the 20-mg dose showed maximum recovery as the minimum dose (e.g., sperm motility 112.03%, testicular cholesterol 34.86%, Bax gene expression 49.77%), whereas 40- and 80-mg doses did not vary statistically with each other (e.g., sperm motility 95.37% and 89.19%, testicular cholesterol 30.42% and 28.41%, Bax gene expression 47.33% and 46.18%, respectively) as well as with the 20-mg dose. It may be concluded that the 20-mg dose is the threshold dose for this purpose. PRACTICAL APPLICATIONS: The hydro-methanol 60:40 extract of rhizomes of Curcuma amada has a strong antioxidant property that can manage diabetes-induced oxidative injuries in testes which may raise a hope to the pharmaceutical industries to develop a herbal drug for diabetes-linked testicular hypofunction management.

Topics: Animals; Antioxidants; Curcuma; Diabetes Complications; Male; Methanol; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Rhizome; Sperm Motility; Testicular Diseases; Testis; Water

The present study aimed to evaluate the protective role of resveratrol and curcumin on oxidative testicular damage induced by di-(2-ethylhexyl) phthalate (DEHP). Male Wistar rats were divided into six groups; three groups received oral daily doses of DEHP (2g/kgBW) for 45days to induce testicular injury. Two of these groups received either resveratrol (80mg/kgBW) or curcumin (200mg/kgBW) orally for 30days before and 45days after DEHP administration. A vehicle-treated control group was also included. Another two groups of rats received either resveratrol or curcumin alone. Oxidative damage was observed by decreased levels of total antioxidant capacity (TAC) and glutathione (GSH) and increased malondialdehyde (MDA) level in the testes of DEHP-administered rats. Serum testosterone level as well as testicular marker enzymes activities; acid and alkaline phosphatases (ACP and ALP) and lactate dehydrogenase (LDH) showed severe declines. DEHP administration caused significant increases in the testicular gene expression levels of Nrf2, HO-1, HSP60, HSP70 and HSP90 as well as a significant decrease in c-Kit protein when compared with the control group. Histopathological observations provided evidence for the biochemical and molecular analysis. These DEHP-induced pathological alterations were attenuated by pretreatment with resveratrol and curcumin. We conclude that DEHP-induced injuries in biochemical, molecular and histological structure of testis were recovered by pretreatment with resveratrol and curcumin. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties along with boosting Nrf2, HSP 60, HSP 70 and HSP 90 gene expression levels and as such may be useful potential tools in combating DEHP-induced testicular dysfunction.

Topics: Alkaline Phosphatase; Animals; Antioxidants; Curcumin; Diethylhexyl Phthalate; Gene Expression; Glutathione; Heat-Shock Proteins; Heme Oxygenase-1; Male; Malondialdehyde; Protective Agents; Rats; Rats, Wistar; Resveratrol; Stilbenes; Testicular Diseases; Testis; Testosterone

The aim of this study was to determine the antioxidative effect of curcumin on nicotine-induced mice testis.. Sixty Swiss albino male mice were divided into five groups, each containing 12 mice. The first group was used as a control. To induce toxicity in the second and third group, nicotine (0.4 mg/kg/day) was injected intraperitoneally into mice for 14 and 28 days, respectively. The mice in the fourth and fifth group were injected with nicotine (0.4 mg/kg/day) and orally treated with curcumin (200 mg/kg) for 14 and 28 days, respectively. Testosterone levels were measured from blood samples and testis tissues were examined under light and electron microscopes.. Light and electron microscopic examinations of the nicotine-induced groups showed evident degenerations in spermatogenic cells, Sertoli cells, and Leydig cells. The groups treated with curcumin had less testicular alterations. The mice that were sacrificed after 28 days in the groups treated with curcumin showed minor degenerations. Furthermore, the median levels of testosterone significantly decreased in the nicotine-induced groups in comparison with those in the control group.. The results indicated that curcumin might be a potential therapeutic agent for testicular injury caused by nicotine addiction.

Topics: Animals; Curcumin; Humans; Leydig Cells; Male; Mice; Nicotine; Testicular Diseases; Testis; Testosterone

Cadmium (Cd) is one of the environmental pollutants affecting various tissues and organs including testis. The aim of this study was to investigate the anti-apoptotic effects of curcumin (Cur) on Cd-induced apoptosis in rat testes. The rats were randomly allotted into one of three experimental groups: control, Cd treated and Cd treated with Cur; each group contained 10 animals. The control group received 2 ml/day of dimethyl sulfoxide (DMSO). To induce toxicity, Cd (1 mg/kg body weight) was dissolved in normal saline and subcutaneously injected into rats for 4 weeks. The rats in Cur-treated group was given a daily dose of 100 mg/kg of Cur for 4 weeks. To date, no examinations of the anti-apoptotic properties of Cur on Cd-induced apoptosis in rat testes have been reported. The mean seminiferous tubule diameter, mean testicular biopsy score values and serum testosterone levels were significantly decreased in Cd-treated groups were compared to the control group. Furthermore, the Cur-treated animals showed an improved histological appearance and serum testosterone levels in Cd-treated group. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling in testis tissues of the Cd-treated group with Cur therapy. The present study showed that Cur treatment protected testes against toxic effects of Cd. We believe that further preclinical research into the utility of Cur may indicate its usefulness as a potential treatment on the spermatogenesis after testicular injury caused by Cd-treated rats.

Topics: Animals; Apoptosis; Cadmium; Curcumin; Drug Interactions; Male; Rats; Rats, Wistar; Seminiferous Tubules; Spermatogenesis; Statistics, Nonparametric; Testicular Diseases; Testis; Testosterone

Metronidazole (MTZ), an anti-parasitic drug, induces negative effects on the testis. Curcumin exhibits antioxidant properties and anti-tumor properties. The aim was to evaluate negative effects of seminiferous tubules and Leydig cells by MTZ and ameliorative effects of curcumin. Balb/c mice were divided into six groups. The control, second, third, fourth and fifth, and sixth groups were administrated distilled water, high doses of MTZ (500 mg/kg/day), MTZ (500 mg/kg/day) +100 mg/kg/day curcumin, therapeutic doses of MTZ (165 mg/kg/day), MTZ (165 mg/kg/day) +100 mg/kg/day curcumin, and 100 mg/kg/day curcumin, respectively. The data revealed significant reduction in tubule volume, length and diameter and germinal epithelium height, and increase the number of Leydig cells in MTZ-treated (high or therapeutic doses) animals. Combined treatment of curcumin with high or therapeutic doses of MTZ ameliorated the increase in number of Leydig cell. Ameliorative effects of curcumin on the other above-mentioned parameters were observed in mice receiving therapeutic doses of MTZ. Leydig cell or nucleus volume and interstitial tissue volume did not show any significant difference in the MTZ-treated mice. It can be concluded that metronidazole can changes structural parameters of the tubules and number of Leydig cells and curcumin can ameliorate these effects.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antiprotozoal Agents; Body Weight; Cell Count; Curcumin; Leydig Cells; Male; Metronidazole; Mice; Mice, Inbred BALB C; Organ Size; Seminiferous Tubules; Testicular Diseases; Testis

The present study was carried out to evaluate the ameliorative effects of kolaviron (a biflavonoid from the seeds of Garcinia kola) and curcumin (from the rhizome, Curcuma longa L.) on the di-n-butylphthalate (DBP)-induced testicular damage in rats. Administration of DBP to rats at a dose of 2 g/kg for 9 days significantly decreased the relative testicular weights compared to the controls, while the weights of other organs remained unaffected. Curcumin or kolaviron did not affect all the organ weights of the animals. While only DBP treatment significantly increased the testicular malondialdehyde level and gamma-glutamyl transferase activity (gamma-GT), it markedly decreased glutathione level, the testicular catalase, glucose-6-phosphate dehydrogenase, superoxide dismutase, sperm gamma-GT activities and serum testosterone level compared to the control group. Data on cauda epididymal sperm count and live/dead ratio were not significantly affected in the DBP-treated rats. Alone, DBP treatment resulted in a 66% decrease in spermatozoa motility and a 77% increase in abnormal spermatozoa in comparison to control. DBP-treated rats showed marked degeneration of the seminiferous tubules with necrosis and defoliation of spermatocytes. The DBP-induced injuries in biochemical, spermatological parameters and histological structure of testis were recovered by treatment with kolaviron or curcumin. The pattern in the behaviour of these compounds might be correlated with their structural variations. Our results indicate that kolaviron and curcumin protect against testicular oxidative damage induced by DBP. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties and as such may prove useful in combating phthalate-induced reproductive toxicity.

Topics: Animals; Antineoplastic Agents; Chemoprevention; Curcuma; Curcumin; Dibutyl Phthalate; Environmental Pollutants; Flavonoids; gamma-Glutamyltransferase; Garcinia kola; Glutathione; Male; Malondialdehyde; Oxidative Stress; Plant Extracts; Plasticizers; Rats; Rats, Wistar; Sperm Motility; Spermatozoa; Testicular Diseases; Testis