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In this study, we investigated the effects of administration of gallic acid (Gal) with or without curcumin (Cur) on the sperm output, steroid level and antioxidant defenses in rat testis in vivo and the expression of inflammatory responsive genes in vitro. Male Wistar rats were divided randomly into four groups and given oral Gal (100mg/kg/day) and Cur (100mg/kg/day) alone or in combination for four weeks. The sperm quality was impaired following Gal treatment, while Cur prevented this and also improved the sperm count as well as the efficiency of sperm production (DSP/gm testis). The inhibitory effects of Gal on plasma testosterone level, glutathione levels, activities of glutathione peroxidase, catalase, superoxide dismutase and steroidogenic enzymes, 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-HSD in the rat testis was blocked by Cur. Interestingly, the level of testosterone and the activities of the steroidogenic enzymes were significantly increased after treatment with Cur alone. Malondialdehyde concentration was unchanged following Gal treatment, while a significant decrease in malondialdehyde level was observed following treatment with Cur alone or in combination with Gal. We further analyzed the effects of Cur and Gal (25-100 μM) on the 93RS2 Sertoli cell-lines and observed that Cur blocked the Gal-induced suppression of inflammatory mediators such as TNF-α and IL-6, while Gal blocked the suppressive effect of Cur on IL-1α expression. Furthermore, the stimulatory or inhibitory effects of Gal on the expressions Tgf-β1 and CD-14 was concentration-dependent and could be blocked by Cur. When cultures of primary Sertoli cells were exposed to both Cur and Gal for 24h, p-JNK/SAPK expression remain stable, whereas Gal-induced p-p65 (NF-κB) expression and IκBα degradation was seen to be blocked by Cur but not Gal-induced expression of pERK1/2. Overall, Cur has stimulatory reproductive effects and could protect the testis from the toxic effects of Gal by mechanisms that could not be explained by its effects on the expressions of inflammatory cytokines but by its anti-oxidant properties., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The present study evaluated the protective effect of ascorbic acid (ASCB) against gasoline fumes (PET) induced testicular oxidative stress, sperm toxicity, and testosterone imbalance in Wistar rats. Twenty-four (24) male albino rats (75 ± 16 g) were randomized into three experimental groups (N = 8). The control group: received normal saline, PET group: exposed to PET 6 h daily by inhalation in an exposure chamber and PET + 200 mg ASCB/kg body weight group: exposed to PET 6 h daily by inhalation and administered ASCB per os. Treatment of ASCB and PET exposure was done thrice and five times weekly for a period of 10 weeks respectively. ASCB co-treatment prevented PET-induced increases in the oxidative stress markers (glutathione, glutathione S -transferase, superoxide dismutase, catalase, hydrogen peroxide generation, nitric oxide, and lipid peroxidation) and serum testosterone concentration (p <.05). Sperm quality was low and those with damaged heads and tails increased alongside histological injuries in the PET-exposed rats, which were also minimized with ASCB administration. ASCB protected against PET-induced oxidative stress, sperm, and testis damage in rats. [ABSTRACT FROM AUTHOR]

In this study, we performed the stereological examination of rat testes and evaluated the protective effect of testosterone against atrazine (ATZ) toxicity in TM3 Leydig and TM4 Sertoli cells. Testosterone intake in rats increased the volumetric density of the seminiferous tubules; tubular diameter; germinal epithelial height; number of spermatogonia, primary and secondary spermatocytes, round spermatids, Sertoli cells, and Leydig cells; and Johnsen scores compared with the values after ATZ treatment (p < 0.05). Furthermore, testosterone increased the viability of TM3 cells and reduced reactive oxygen species (ROS) generation in TM4 cells compared to the ATZ‐treated group. In conclusion, exogenous testosterone intake maintains testicular morphometry and spermatogenesis in rats, and minimizes cell death and ROS generation in testicular cell lines exposed to ATZ. However, TM4 cells are more responsive to testosterone‐mediated regulation of ROS generation induced by ATZ than TM3 cells. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the protective effect of fluted pumpkin seeds (FPS) against caffeine (CAFF) induced testicular toxicity in rats. Thirty young healthy male Wistar rats (196 ± 12 g) were randomly organized into five sets of six animals per each group: control, caffeine (CAFF; 50 mg kg−1 bw) and FPS co‐treatment groups (CAFF + 50 mg FPS, CAFF + 100 mg FPS and CAFF + 200 mg FPS kg−1 bw). CAFF and FPS were administered daily and twice per week respectively by oral gavage for 40 days. CAFF treatment decreased testicular lactate dehydrogenase enzyme activity level, which was attenuated on co‐administration with FPS at 50 and 100 mg kg−1 bw. Furthermore, CAFF decreased seminiferous epithelia thickness and spermatogenesis score index and increased the number of tubules with abnormal histological features, which were attenuated on co‐administration with FPS at 50 mg kg−1 bw much more than at the higher doses (p < 0.05). CAFF did not affect malondialdehyde and glutathione concentrations and glutathione peroxidase (GSH‐Px) activity in the testes whereas FPS co‐treatment at the higher doses elevated glutathione level and GSH‐Px activity and did not affect spermatogenesis score index at the highest dose (200 mg kg−1 bw). Testicular malondialdehyde concentrations remained unaffected in all FPS co‐treatment groups. Overall, FPS is able to minimize the CAFF‐induced testicular injury at lower than at the higher tested doses. [ABSTRACT FROM AUTHOR]

This study examined the effects of cadmium (Cd) on the testes of rats and the efficacy of fluted pumpkin seeds (FPS) supplementation. Twenty-four adult male rats (150–190 g) were allocated into four groups. I: control; corn oil (2 ml/kg); II: Cd (24 mg/kg); III: Cd (24 mg/kg) + FPS (25 mg/kg); IV: Cd (24 mg/kg) + FPS (250 mg/kg). After 44 days, the rats were killed and testes and serum were isolated for experimental analysis. Cd treatment significantly increased the concentrations of malondialdehyde, nitric oxide, and abnormal histological features (Sertoli cells-only tubules, atrophy, spermatogenesis arrest, and a reduced Johnsen's score). It also decreased the antioxidant defense of the testes and serum testosterone concentration. FPS extracts at both doses were able to recover spermatogenesis and steroidogenesis and inhibit oxidative stress caused by Cd. [ABSTRACT FROM AUTHOR]

Here, we studied the protective effect of gallic acid (GAL) as a potent anti-oxidant and anti-inflammatory agent against damage caused by busulfan (BUS) in the testes of adult rats. The adult Wistar rats were assigned as control, BUS: was intraperitoneally (i.p.) treated with busulfan (15 mg/kg, day 7 and 14), GAL + BUS: was co-treated with busulfan (i.p., 15 mg/kg, day 7 and 14) and orally treated (per os) with gallic acid (60 days, 20 mg/kg) and GAL: was treated with gallic acid (per os, 60 days, 20 mg/kg). The results showed that GAL co-treatment increased the numbers of spermatogonia (Type A and B), spermatocytes (primary and secondary) and round spermatids, along with the tubular diameter, epithelial height and gonado-somatic index. In addition, BUS-induced increase in 3β-hydroxysteroid dehydrogenase and γ-glutamyl transpeptidase activities were inhibited on GAL co-treatment. Similarly, BUS-induced decrease in gluthathione concentration, catalase and superoxide dismutase activities along with increase in myeloperoxidase activity and malondialdehyde concentration were significantly normalized to control values on GAL co-treatment. Busulfan-induced elimination of tubular germ cells was completely prevented by GAL. Overall, GAL may inhibit BUS-mediated spermatogenesis arrest via decreasing inflammatory-mediated oxidative stress in a rat experimental model. [ABSTRACT FROM AUTHOR]

Here, we studied the protective effect of rutin (RUT) against testicular damage caused by busulfan (BUS) in rats. Adult male Wistar rats were intraperitoneally injected with BUS (4 mg/kg body weight at day 7 and 14), and then treated with RUT (30 mg/kg body weight) by gavage thrice weekly for 60 days. The results showed that BUS-induced increase in 3β-hydroxysteroid dehydrogenase (3β-HSD) was significantly decreased by RUT, whereas 17β-HSD activity and plasma testosterone concentration remained unaffected (p > 0.05). It was also observed that RUT inhibited BUS-induced increase in nitrite concentrations and myeloperoxidase enzyme activities in the plasma and testes (p < 0.05). Similarly, BUS-induced decrease in glutathione and increase in malondialdehyde concentrations in the testes were significantly normalized to control values by RUT. Finally, RUT administration showed some tendency to improve the architecture of the seminiferous epithelium of the rat's testes after BUS treatment. Overall, RUT inhibited BUS-induced oxidative damage and inflammation in the testis of an experimental rat model. [ABSTRACT FROM AUTHOR]

The present study evaluated the protective effect of fluted pumpkin seeds (FPS) on atrazine (ATZ)-induced testicular damage. Twenty adult male Wistar rats were divided into four groups of five animals each. The control animals (Group A) received corn oil (2 mL/kg body weight), Group B animals received 50 mg ATZ/kg body weight by gavage, while Groups C and D received 50 mg ATZ/kg body weight once a week in addition to the gavage of 25 mg FPS/kg body weight and 50 mg FPS/kg body weight respectively for 60 days. The results showed that testicular myeloperoxidase activity and nitrite concentration were decreased in all groups compared to the control value. The increase in malondialdehyde and decrease in glutathione concentrations in group B were abrogated in group C (p < 0.05) but not in group D animals. The increase in γ-glutamyl transpeptidase and decrease in lactate dehydrogenase enzyme activities in the group B animals were also normalized to control values in group C but not in group D animals. Interestingly, the testis of the group D animals showed massive depletion of germ cells and the diameter of the seminiferous tubules of these animals were decreased compared to all other groups. However, the number of motile sperms, abnormal sperms and sperm count in Group D animals were similar to the ATZ-treated animals and lower than control values. In conclusion, FPS protected against ATZ-induced testicular damage but can also harm the testis at a higher dose. [ABSTRACT FROM AUTHOR]

[Display omitted] • Atrazine exposure decreased Leydig cell's 3β-HSD expression. • Caspase-3 expression in Leydig cells was increased by atrazine. • TUNEL staining confirms apoptotic Leydig cells death by atrazine. • Testosterone level was decreased by atrazine. • Leydig cell is the primary target for atrazine in the testis. Several studies have reported the effects of atrazine on the gonads of many experimental models. However, the short-term effects of in vivo exposure to atrazine on the testes of mice are not well clarified. Here we reported that adult BalB/c mice exposed to atrazine (50 mg kg−1 body weight) by gavage for three consecutive days have reduced numbers of 3β-hydroxysteroid dehydrogenase positive Leydig cells (LCs), associated with increased in situ cell death fluorescence and caspase-3 immuno-expression in the testes. Consequently, immunostaining for cell cycle gene regulators showed increased expressions of p45, accompanied with increased expressions of cyclin D2 and E2. Histological observations of the gonads showed reduced number of germ cells in particular areas, sloughed seminiferous epithelium, presence of giant apoptotic cells close to the seminiferous tubule lumen and in the epididymal lumen along with low numbers of Leydig cells in the testicular interstitial areas. Similarly, LCs isolated from the testes of BalB/c mice that were exposed to atrazine (0.5, 25, 50 mg kg−1 body weight) in the same manner as in the first experiment presented dose-dependent increased caspase-3 activity, decreased cell viability, intratesticular and serum testosterone concentrations and LCs testosterone secretion. In summary, atrazine appears to directly decrease the number of testosterone secreting LCs in mice through apoptosis. [ABSTRACT FROM AUTHOR]

AbstractGallic acid (GAL), rutin (RUT), and quercetin (QUE) are common antioxidant agents in fruits and vegetables with intriguing pharmacological effects. In the present study, we compared the therapeutic outcomes of GAL + QUE in comparison with GAL + RUT co-treatment in a busulfan (BUS) model of testicular injury in Wistar rats. BUS (4 mg kg−1 body weight (b.w) was injected intraperitoneally daily for 4 days. GAL + RUT or GAL + QUE (20 mg kg−1 b. w) was delivered by oral gavage for 52 days. Examination of the testes of BUS-treated rats both biochemically and under light microscopy revealed an increased level of lipid peroxidation, DNA fragmentation, glutathione-S-transferase, lactate dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase and acid phosphatase with a concomitant decrease in the level of antioxidants: glutathione, ascorbic acid, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, suggesting testicular injury. Tissue sections confirmed the testicular injury-induced by BUS, including diminished spermatogenesis score index, tubular diameter, gonado-somatic index, testis weight, epithelia thickness and higher percentage of aberrant tubules. GAL + QUE co-administration had better recovery effects than GAL + RUT on the biochemical markers and protected against BUS-induced testicular damage. GAL + QUE treatment regimen has better capacity to maintain the antioxidant capacity of the testes and is more potent at reducing BUS-induced oxidative damage compared to GAL + RUT. [ABSTRACT FROM AUTHOR]