Lycopene protects against cyclosporine A-induced testicular toxicity in rats

Cyclosporine A (CsA)-induced direct failures in hypothalamic–pituitary–gonadal axis and Sertoli cell phagocytic function have been considered for testicular toxicity so far. It has clearly been reported that oxidative stress leads to damage in sperm functions and structure of the testis. Therefore, this study was conducted to demonstrate whether CsA causes testicular and spermatozoal toxicity associated with the oxidative stress, and to investigate the possible protective effect of lycopene against CsA-induced damages in all reproductive organs and sperm characteristics in male rats. While the daily administration of CsA at the dose 15 mg/kg for 21 days significantly decreased the seminal vesicles weight, epididymal sperm concentration, motility, testicular tissue glutathione (GSH), glutathione peroxidase (GSH-Px) and catalase (CAT), diameter of seminiferous tubules and germinal cell thickness, it increased malondialdehyde (MDA) level and abnormal sperm rates along with degeneration, necrosis, desquamative germ cells in testicular tissue. However, the CsA along with simultaneous administration of lycopene at the dose of 10 mg/kg markedly ameliorated the CsA-induced all the negative changes observed in the testicular tissue, sperm parameters and oxidant/antioxidant balance. In conclusion, CsA-induced oxidative stress leads to the structural and functional damages in the testicular tissue and sperm quality of rats and, lycopene has a potential protective effect on these damages

Lycopene and ellagic acid prevent testicular apoptosis induced by cisplatin

The aim of this studywasto investigate the possible protective effects of lycopene (LC) and ellagic acid (EA) on cisplatin (CP)-induced testicular apoptosis in male rats. The control group was treated with placebo; LC, EA and CP groups were given alone LC, EA and CP, respectively; the CP + LC group was treated with a combination of CP and LC; and the CP + EAgroup was treated with a combination of CP and EA. Although CP significantly increased the number of Bax-positive (apoptotic) cells it had no effect on the number of Bcl- 2-positive (antiapoptotic) cells compared with the control group. Administration of CP caused significant increase in lipid peroxidation and nonsignificant decrease in superoxide dismutase (SOD) activity along with some histopathological lesions in testicular tissue. However, combined treatments of LC or EA in addition to CP tended to prevent the CP-induced testicular apoptosis, histopathological lesions and lipid peroxidation

Attenuating effect of lycopene and ellagic acid on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced spermiotoxicity and testicular apoptosis

This study was conducted to investigate the prophylactic effects of lycopene (LC) and ellagic acid (EA) on 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD)-induced testicular and spermatozoal toxicity. These toxicological changes are associated with the oxidative stress and apoptosis in male rats. Forty-eight male rats were allocated to one of six groups of 8 rats each: control, LC, EA, TCDD, TCDD+LC, and TCDD+EA. The control group was treated with 0.5 mL/ rat slightly alkaline solution+0.5 mL/rat corn oil every other day. The LC group was treated with 0.5 mL/rat slightly alkaline solution+0.5 mL/rat corn oil containing 10 mg/kg of LC every other day. The EA group received 0.5 mL/rat corn oil+0.5 mL/rat slightly alkaline solution containing 2 mg/kg of EA every other day. The TCDD group received 0.5 mL/rat corn oil containing 100 ng/kg/day of TCDD+0.5 mL/rat slightly alkaline solution. The TCDD+LC group was treated with 0.5 mL/rat TCDD+0.5 mL/rat LC. The TCDD+EA group was treated with 0.5 mL/rat TCDD+0.5 mL/rat EA. All treatments were made by gavage, and the experimental period was maintained during 8 weeks. Sperm motility, concentration, and abnormal sperm rate in epididymal tissue, testicular tissue lipid peroxidation (LPO), antioxidant enzyme activity, histopathological changes, and apoptosis (i.e., Bax and Bcl-2 proteins) were determined. TCDD exposure resulted in significant decreases in sperm motility, concentration, testicular superoxide dismutase activity, germinal cell-layer thickness, Johnsen’s testicular score, and significant increases in abnormal sperm rate, testicular malondialdehyde, glutathione levels, Bax-positive staining, and Bax-positive apoptotic cell score, along with some testicular histopathological lesions. TCDD treatment did not affect significantly catalase activity. However, combined treatment with LC or EA, in addition to TCDD, prevented the development of TCDD-induced damages in sperm quality, testicular histology, and LPO. Improvements in testicular apoptosis after the administration of LC and EA to TCDD-treated rats were minimal, but not statistically significant. TCDD-induced lipid peroxidation leads to functional and structural damages, as well as apoptosis, in spermatogenic cells of rats. Both LC and EA protected against the development of these effect

Improvement of cisplatin-induced injuries to sperm quality, the oxidant-antioxidant system, and the histologic structure of the rat testis by ellagic acid

Objective: To investigate whether ellagic acid (EA) has a possible protective effect against cisplatin (CP)-induced negative changes in epididymal sperm characteristics and the histologic structure of testis and prostate associated with oxidative stress in rats. Design: Experimental study. Setting: Fırat University Medical School Experimental Research Center, Elazı g, Turkey. Patient(s): Eight-week-old adult male Sprague Dawley rats (n ¼ 24). Intervention(s): Cisplatin was administered to rats at a single dose of 7 mg/kg IP. Ellagic acid was administered both separately and simultaneously with CP by gavage daily for 10 days at the dose of 10 mg/kg. Main Outcome Measure(s): Reproductive organ weights, epididymal sperm characteristics, and histopathologic structure of testes and ventral prostate were determined along with malondialdehyde (MDA) and glutathione (GSH) levels and glutathione-peroxidase (GSH-Px) and catalase (CAT) activities of plasma, sperm, and testicular tissue. Result(s): Ellagic acid ameliorated the CP-induced reductions in weights of testes, epididymides, seminal vesicles, and prostate along with epididymal sperm concentration and motility. Additionally, EA decreased the CP-induced increments in abnormalities of sperm. Whereas CP increased the MDA levels of plasma, sperm, and testicular tissue, it decreased the GSH-Px and CATactivities in the study samples compared with the control group. The administration of EA to CP-treated rats decreased the MDA level and increased GSH-Px and CATactivities in these samples. Cisplatin caused degeneration, necrosis, interstitial edema, and reduction in germinative cell layer thickness and rarely reduction in spermatogenic activity in some seminiferous tubules. The CP-induced changes in histopathologic findings of testis were partially reversed by treatment with EA. No significant changes were observed in the histopathologic structure of the prostate among any of groups. Conclusion(s): Ellagic acid has a protective effect against testicular toxicity caused by CP. This protective effect of EA seems to be closely involved with the suppressing of oxidative stress

Attenuation of cyclosporine A-induced testicular and spermatozoal damages associated with oxidative stress by ellagic acid

This study was conducted to investigate the possible protective effect of ellagic acid (EA) on cyclosporine A (CsA)-induced testicular and spermatozoal damages associated with oxidative stress in male rats. Forty adult male Sprague–Dawley rats were divided into 4 groups of 10 animals each. Control group was used as placebo. Cyclosporine group received CsA at the dose of 15 mg/kg/day. Ellagic acid group was treated with EA (10 mg/kg/day). Cyclosporine plus ellagic acid group received CsA+EA. Reproductive organs were weighed and epididymal sperm characteristics and histopathological structure of testes were examined along with malondialdehyde (MDA) and glutathione (GSH) levels, glutathione-peroxidase (GSH-Px) and catalase (CAT) activities in testicular tissue. CsA significantly decreased the weights of testes and ventral prostate, epididymal sperm concentration, motility, testicular tissue glutathione (GSH), glutathioneperoxidase (GSH-Px) and catalase (CAT), diameters of seminiferous tubules and germinal cell layer thickness, and it significantly increased malondialdehyde (MDA) level and abnormal sperm rates along with degeneration, necrosis, immature germ cells, congestion and atrophy in testicular tissue. However, the CsA plus EA treatment attenuated all the CsA-induced negative changes observed in the testicular tissue, sperm and oxidant/antioxidant parameters. In conclusion, CsA-induced oxidative stress leads to the structural and functional damages in the testicular tissue and sperm quality of rats, and also EA has a protective effect on these damages

Antiperoxidative and anti-apoptotic effects of lycopene and ellagic acid on cyclophosphamide-induced testicular lipid peroxidation and apoptosis

The present study was conducted to investigate the possible protective effects of lycopene (LC) and ellagic acid (EA) on cyclophosphamide (CP)-induced testicular and spermatozoal toxicity associated with the oxidative stress and apoptosis in male rats. Forty-eight healthy adult male Sprague-Dawley rats were divided into six groups of eight rats each. The control group was treated with placebo; the LC, EA and CP groups were given LC (10 mg kg−1), EA (2 mg kg−1) and CP (15 mg kg−1), respectively, alone; the CP+LC group was treated with a combination of CP (15 mg kg−1) and LC (10 mg kg−1); and the CP+EA group was treated with a combination of CP (15 mg kg−1) and EA (2 mg kg−1). All treatments were maintained for 8 weeks. At the end of the treatment period, bodyweight and the weight of the reproductive organs, sperm concentration and motility, testicular tissue lipid peroxidation, anti-oxidant enzyme activity and apoptosis (i.e. Bax and Bcl-2 proteins) were determined. Administration of CP resulted in significant decreases in epididymal sperm concentration and motility and significant increases in malondialdehyde levels. Although CP significantly increased the number of Bax-positive (apoptotic) cells, it had no effect on the number of Bcl-2-positive (anti-apoptotic) cells compared with the control group. However, combined treatment of rats with LC or EA in addition to CP prevented the development of CP-induced lipid peroxidation and sperm and testicular damage. In conclusion, CP-induced lipid peroxidation leads to structural and functional damage, as well as apoptosis, in spermatogenic cells of rats. Both LC and EA protect against the development of these detrimental effects

Remote organ injury induced by myocardial ischemia and reperfusion on reproductive organs, and protective effect of melatonin in male rats

Objective: Myocardial ischemia and reperfusion (MI-R) leads to remote organ injury associated with oxidative stress. Melatonin is a well-known antioxidant and free-radical scavenger. This study was conducted to examine whether MI-R causes damage in the testes and sperm quality, and to investigate the possible protective effect of exogenous melatonin on these parameters in an in vivo rat model. Design: Experimental study. Setting: Experimental Research Center, Fırat University Medical School, Elazıg˘, Turkey. Patient(s): Eight-week-old male Wistar rats (n 18). Intervention(s): To produce MI-R, a branch of the descending left coronary artery was occluded for 30 minutes, followed by 120-minute reperfusion. Melatonin (10 mg/kg) or vehicle was given 10 minutes before ischemia via the jugular vein. Main Outcome Measure(s): Reproductive organ weights and epididymal sperm concentration, sperm motility, abnormal sperm rate, and testicular-tissue malondialdehyde (MDA) and glutathione (GSH) levels were examined after reperfusion. Result(s): MI-R significantly decreased epididymal sperm motility, and increased the testes-tissue level of MDA, compared to the control group. Administration of melatonin reversed the harmful effects of MI-R significantly. However, MI-R did not change sperm concentration, GSH levels, and reproductive organ weights. Conclusion(s): These findings indicate that MI-R leads to damage of testis tissue and sperm motility, and melatonin protects against MI-R-induced reproductive-organ injury. These results may also encourage the use of antioxidants to reduce remote organ injury in the testis after MI-R

Improvement of cisplatin-induced injuries to sperm quality, the oxidant-antioxidant system, and the histologic structure of the rat testis by ellagic acid

Objective: To investigate whether ellagic acid (EA) has a possible protective effect against cisplatin (CP)-induced negative changes in epididymal sperm characteristics and the histologic structure of testis and prostate associated with oxidative stress in rats. Design: Experimental study. Setting: Fırat University Medical School Experimental Research Center, Elazı g, Turkey. Patient(s): Eight-week-old adult male Sprague Dawley rats (n ¼ 24). Intervention(s): Cisplatin was administered to rats at a single dose of 7 mg/kg IP. Ellagic acid was administered both separately and simultaneously with CP by gavage daily for 10 days at the dose of 10 mg/kg. Main Outcome Measure(s): Reproductive organ weights, epididymal sperm characteristics, and histopathologic structure of testes and ventral prostate were determined along with malondialdehyde (MDA) and glutathione (GSH) levels and glutathione-peroxidase (GSH-Px) and catalase (CAT) activities of plasma, sperm, and testicular tissue. Result(s): Ellagic acid ameliorated the CP-induced reductions in weights of testes, epididymides, seminal vesicles, and prostate along with epididymal sperm concentration and motility. Additionally, EA decreased the CP-induced increments in abnormalities of sperm. Whereas CP increased the MDA levels of plasma, sperm, and testicular tissue, it decreased the GSH-Px and CATactivities in the study samples compared with the control group. The administration of EA to CP-treated rats decreased the MDA level and increased GSH-Px and CATactivities in these samples. Cisplatin caused degeneration, necrosis, interstitial edema, and reduction in germinative cell layer thickness and rarely reduction in spermatogenic activity in some seminiferous tubules. The CP-induced changes in histopathologic findings of testis were partially reversed by treatment with EA. No significant changes were observed in the histopathologic structure of the prostate among any of groups. Conclusion(s): Ellagic acid has a protective effect against testicular toxicity caused by CP. This protective effect of EA seems to be closely involved with the suppressing of oxidative stress

Impact of ellagic acid on adriamycin-induced testicular histopathological lesions, apoptosis, lipid peroxidation and sperm damages

The aim of the present study was to investigate whether ellagic acid (EA) has protective effect on adriamycin (ADR)-induced testicular and spermatozoal toxicity associated with the oxidative stress in male rats. Thirthy-two healthy 8-week-old male Sprague–Dawley rats were equally divided into four groups. The first (EA) group was treated with EA (2 mg/kg/every other day) by gavage. The second (ADR) group received ADR (2 mg/kg/once a week) intraperitoneally, while the combination of ADR and EA was given to the third (ADR + EA) group. The forth (control) group was treated with placebo. At the end of the 8- week treatment period, reproductive organ weights, epididymal sperm parameters, histopathological changes and apoptosis via Bax and Bcl-2 proteins, testicular tissue lipid peroxidation, and antioxidant enzyme activities, were investigated. ADR administration was determined to cause significant decreases in reproductive organ weights, epididymal sperm concentration and motility, plasma testosterone concentration, diameter of seminiferous tubules, germinal cell layer thickness, Johnsen’s testicular score and Bcl-2 positive antiapoptotic cell rate, wherease it caused significant increases in level of lipid peroxidation and glutathione, catalase activity, abnormal sperm rates and Bax positive apoptotic cell rates along with degeneration, necrosis, immature germ cells, congestion and atrophy in testicular tissue when compared with the control group. EA administration to ADR-treated rats provided significant improvements in ADR-induced disturbed oxidant/antioxidant balance, decreased testosterone concentration, testicular apoptosis and mild improvements in the histopathological view of the testicular tissue. However, EA failed to improve decreased reproductive organ weights and deteriorated sperm parameters due to ADR administration. It is concluded that while ADR has direct or indirect (lipid peroxidation) negative effects on sperm structure and testicular apoptosis in rats, EA has protective effects on ADR-induced testicular lipid peroxidation and apoptosis