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There are few treatment options, including the use of natural phenolics-based combination therapy for mitigating male infertility conditions associated with chemotherapy. Busulfan is an anti-cancer drug that leads to testicular problems in humans. Here, we studied the effect of co-treatment of rutin and kolaviron against busulfan-induced testis damage. Young adult male Wistar rats were intraperitoneally injected busulfan (4 mg/kg b.w), and then orally administered rutin (30 mg/kg b.w), and kolaviron (50 mg/kg b.w) alone and combined for 60 days. Results revealed that rutin and kolaviron alone or in combination reversed busulfan-induced increase in oxidative stress along with sperm quality of treated animals. However, kolaviron and rutin separately improved the concentrations of MDA and GSH and sperm quality more than when they were combined. Similarly, rutin and kolaviron separately or in combination preserved spermatogenesis and relieved busulfan-induced increase in nitric oxide concentration, myeloperoxidase and 3β-hydroxysteroid dehydrogenase activities. Co-supplementation with kolaviron but not rutin nor when rutin was combined with kolaviron also improved the testicular level of tumor necrosis-alpha. Finally, the histological features in the testes caused by busulfan were reversed by rutin, whereas treatment with kolaviron alone or in combination with rutin partially protected the testis from busulfan-induced injury as demonstrated by the appearance of few germ cells, damaged tubules, loss of round spermatids and defoliation of the seminiferous epithelium. Thus, the combined treatment regimen of rutin and kolaviron sparingly prevented busulfan-induced testicular injuries in rats. Abbreviations: CAT: Catalase; GSH: Glutathione; 3β-HSD: 3β- hydroxysteroid Dehydrogenase; MDA: Malondialdehyde; TNF-α: Tumor necrosis-alpha; BUS: Busulfan; RUT: Rutin; KV: Kolaviron; TBARS: Thiobarbituric Acid Reactive Substances; MPO: Myeloperoxidase; ELISA: Enzyme-Linked Immunoassay; NAD: Nicotinamide Adenine Dinucleotide (oxidized); ROS: Reactive Oxygen Species.

Objective: To investigate the effects of different extracts of Anthocleista djalonensis on the testis and epididymal sperms of rats., Methods: Fifty male Wistar rats were randomly divided into 10 groups (n=5 in each group) and orally treated with 50, 100 and 200 mg/kg body weight each of methanol, aqueous ethanol (H-EtOH) and chloroform extracts of A. djalonensis. Corn oil was used as vehicle (2 mL/kg). After 60 days of treatment, testosterone (T) and cholesterol (CHOL) concentrations, catalase (CAT), lactate dehydrogenase (LDH), 3β-hydroxysteroid dehydrogenase (3β-HSD) and superoxide dismutase (SOD) activities in the testes along with myeloperoxidase (MPO) activities and nitrite concentrations (NO) in the serum and testes as well as sperm quality were measured., Results: T and CHOL concentrations along with 3β-HSD activity were significantly higher in the animals treated with the low dose than in those treated with the high dose of the chloroform extract (P<0.05). Furthermore, the chloroform extract was more effective than the methanol extract that had the most marginal effect on T level at the high dose and the H-EtOH extract that was only effective at the medium dose. LDH activity was dose-dependently increased by the extracts in all groups. The CAT-SOD antioxidant system was increased in the treated animals at all doses compared to the control values, but the increase in glutathione level reached significant level in those treated with the low dose H-EtOH aqueous ethanol extract (P<0.05). Only the high dose of chloroform extract had significant inhibitory effects on MPO activity (P<0.05). Serum NO concentration was decreased at all doses of the extracts. The inhibitory effects of the extracts on testicular NO concentrations follow this order, chloroform extract > H-EtOH > methanol. Although all extracts at all doses showed excellent stimulatory effects on sperm quality (count, motility and morphology), the methanol extract at the high dose was the most effective on sperm count (P<0.05)., Conclusion: The chloroform extract of A. djalonensis has better androgen-like and anti-inflammatory effects whereas the methanol extract has the best effect on sperm count.

Both ethanol (EtoH) and atrazine (ATZ) have hepatic and nephro-toxic effects in rats. In the present study, the toxicity of EtoH (5 g kg -1 ) on the kidney and liver in the absence or in the presence of different doses of ATZ (50, 100, 300 mg kg -1 ) was evaluated after 21 days in rats. Results showed that the mixture effects on catalase and superoxide dismutase activities were more severe in both tissues compared to EtoH alone, especially as the dose of ATZ was increased. Hepatic malondialdehyde level (an index of lipid peroxidation) was increased from 20.32% in the EtoH +50 mg kg -1 ATZ-treated rats to 34% in the EtoH +300 mg kg -1 ATZ-treated rats compared to the EtoH values. Renal malondialdehyde values remain as high as 81% in the EtoH-treated rats and the different combine exposure groups. Furthermore, as the dose of ATZ in the mixture was increased, serum uric acid level increased compared to the EtoH values. When the EtoH +300 mg kg -1 ATZ-animals were pretreated with curcumin (an antioxidant), the histopathological changes and peroxidative damages in both tissues were blocked. The exposure of EtoH-treated rats to ATZ enhanced renal and hepatic peroxidative damages in rats.

Curcumin (Cur) and gallic acid (Gal) are major food additives. Cur has well-known antioxidant properties, whereas Gal has both antioxidant and pro-oxidant effects. The present study investigated the effects of oral administration of Gal with or without Cur on antioxidant enzymes activities, glutathione (GSH) and the enzymes in its metabolism in rat liver in vivo and markers of tissue damage in the serum. Results showed that the increase in serum creatinine level, alkaline phosphatase and lactate dehydrogenase activities by Gal treatment were inhibited by combined administration of Gal and Cur. The decrease in GSH-peroxidase, GSH-S-transferase, superoxide dismutase and GSH-reductase activities by Gal treatment were inhibited when both Gal and Cur were administered together. The malondialdehyde concentration and catalase activity were significantly increased following administration of Gal but not when the administration of Gal was combined with Cur. Finally, the increase in GSH level was seen following administration of Cur alone or in combination with Gal but not with Gal alone. These results suggest that Gal might induce oxidative stress in the rat liver and affect renal function that can be inhibited by the combined administration of Gal and Cur.

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 effect of the phytoestrogen, quercetin (QT) on the reproductive toxicity of atrazine (ATZ) was explored in interstitial Leydig cells (ILCs). We measured the mRNA expressions of steroidogenesis genes: steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD), cytochrome-P450 (CYP) 11A1, insulin-like factor 3 (INSL-3), CYP17A1, inhibin-α (INH-α), androgen receptor (AR), estrogen receptor-α (ER-α), and luteinising hormone receptor (LHR) in isolated ILCs by real-time-PCR after cultured cells were treated in vitro with ATZ (232 μM) and QT (50 μM). The mRNA expression of tested genes increased with ATZ treatment and was normalized by quercetin except AR and ER-α expression. Treatment of cells with QT alone (15-50 μM) caused a dose-dependent increase in AR and ER-α mRNA expression. We also found that QT (50 μM) increased the expressions of AR and ER-α in the presence of a sub-threshold level of cyclic-AMP at 1h culture period to the levels seen with maximal stimulation of cyclic-AMP. Furthermore, the expressions of tested genes were unaffected by cyclic-AMP at 6h when the stimulatory effects of ATZ on tested genes were sustained. These findings suggest that ATZ may stimulate the expression of tested steroidogenesis genes in ILCs via a mechanism independent of cyclic-AMP which was partially antagonize by QT., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Quercetin has been reported to protect testicular cells from oxidative damage induced by environmental chemicals. In this study, we isolated interstitial Leydig cells (ILCs) from immature rats, set-up ILCs culture, co-treated cells with atrazine (ATZ) and quercetin (QT), evaluated toxicity, and measured the expression levels of antioxidant enzymes and nuclear factor-kappaB (NF-κB) and levels of steroidogenic enzymes. ATZ decreased ILCs viability at concentrations higher than 10 μg/mL and increased reactive oxygen species, malondialdehyde (MDA), and glutathione levels. ATZ also increased glutathione peroxidase, glutathione reductase, and glutathione-S-transferase and decreased superoxide dismutase-1 (sod1) and superoxide dismutase-2 (sod2) messenger RNA (mRNA) levels which were prevented by QT. The changes in the MDA levels and lactate dehydrogenase leakage induced by ATZ (50 μg/mL) were also prevented on co-treatment with QT (50 μM). Furthermore, ATZ-induced 3β- and 17β-hydroxysteroid dehydrogenase activities and NF-κB-expressions at the mRNA and protein levels were also recovered to control value on co-treatment with QT. These data showed that QT protected against ATZ-induced ILCs toxicity by restoring the expression of NF-κB and steroidogenic activity and by preventing the oxidative stress.

Quercetin (QT), a dietary-derived flavonoid, is ubiquitous in fruits and vegetables and plays an important role in human health by virtue of its antioxidant function. The present study was designed to examine the effects of QT on oxidative damage that was induced by the herbicide, atrazine (ATZ), in mixed cultures of Sertoli-germ cells. Results showed that treatment with QT increased cell viability and decreased catalase activity, malondialdehyde, and reactive oxygen species (ROS) levels. QT treatment also increased the mRNA expression of glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione-S-transferase, and superoxide dismutase-1 and could not reversed to the control levels ATZ-induced steady-state mRNA levels of these antioxidant genes as well as the level of glutathione and activities of GSH-Px and GR. QT has protective effect against ATZ-induced oxidative stress through a reduction in ROS levels and lipid peroxidation., (© 2012 Wiley Periodicals, Inc.)

The present study evaluated the possible protective effects of selenium against atrazine-induced toxicity in the liver and reproductive system of rats. Atrazine administered to rats orally at a dose of 120 mg/kg caused an inhibition in the activity of glutathione-S-transferase and an increase in malondialdehyde formation in the liver, testis and epididymis. Superoxide dismutase decreased in the liver and testis but was increased in the epididymis. Furthermore, hepatic glutathione and lactate dehydrogenase activity increased while epididymal catalase, ascorbate content, hepatic aspartate aminotransferase and glutathione peroxidase activities in all the tissues decreased in the atrazine-treated animals. Hepatic, testicular and epididymal alanine aminotransferase activities were not affected by atrazine (p>0.05). Decreased epididymal and testicular sperm number, sperm motility, daily sperm production and increased number of dead and abnormal sperm were observed in atrazine-treated rats. Treatment of rats orally with selenium at a dose of 0.25 mg/kg did not prevent atrazine-induced changes in sperm characteristics and had no protective effects against atrazine-induced biochemical alterations in the testis and epididymis except testicular lactate dehydrogenase. Catalase activity and ascorbate contents were unchanged in these groups of animals. However, selenium effectively protected against atrazine-induced changes in biochemical indices in the liver. In rats treated with selenium alone, glutathione peroxidase in all the tissues, hepatic glutathione and superoxide dismutase, testicular lactate dehydrogenase activity and ascorbate content increased, while hepatic catalase activities decreased (p<0.05). Our data suggest that selenium effectively attenuated the toxic effects of atrazine-induced liver changes but not in the reproductive organs and sperms of rats. Selenium might therefore be useful in ameliorating oxidative stress in the liver., (Copyright © 2009 Elsevier GmbH. All rights reserved.)

Context: Selenium (Se) and rutin (RUT) are antioxidants that protect against tissue damage. Objective: In this study, the separate and combine protective effects of RUT and Se against cadmium (Cd)-induced renal damage were evaluated in rats. Materials and methods: Wistar rats were treated by gavage to RUT (30 mg/kg) or Se (0.15 ppm) or Cd (200 ppm) in drinking water alone or in combination (30 mg/kg RUT +0.15 ppm Se + 200 ppm Cd). Corn oil was used as vehicle (2 mL/kg). After a 5-week treatment period, rat kidneys were removed for biochemical assays and histopathological examination. Se and Cd levels were evaluated by flame atomic absorption spectrophotometry. Results: The malondialdehyde and glutathione levels as well as superoxide dismutase and catalase activities in the Cd-treated animals were increased compared with control values (0.056 ± 0.0003 versus 0.011 ± 0.0005 μmol/mg; 0.005 ± 0.0006 versus 0.00085 ± 0.0002 μg/mg; 1.62 ± 0.09 versus 0.48 ± 0.12 units/mg; 650 ± 25 versus 361.89 ± 31 μmol H2O2/mg, respectively). Cd treatment was also associated with decreased renal Se concentration (4.19 ± 0.92 versus 7.73 ± 0.7 μg/g dry weight), increased alkaline phosphatase (0.07 ± 0.0015 versus 0.033 ± 0.0019 unit/mg), acid phosphatase (0.029 ± 0.0021 versus 0.015 ± 0.0016 unit/mg), and lactate dehydrogenase (0.032 ± 0.004 versus 0.014 ± 0.0027 unit/mg) activities, respectively, and with evidence of severe renal damage. The combination of RUT and Se or their separate effects prevented the Cd-induced oxidative renal damage. However, their combine effects do not have stronger effects than their separate effect against Cd-induced renal damage. Discussion and conclusion: RUT and Se function as potent antioxidant in the protection of renal damage induced by Cd. [ABSTRACT FROM AUTHOR]