Rutin ameliorates cisplatin‐induced reproductive damage via suppression of oxidative stress and apoptosis in adult male rats

Cisplatin (CP) treatment causes damage in the male reproductive system. Rutin (RUT) is a naturally occurring flavonoid glycoside that has antioxidant and anti‐inflammatory properties. This study aimed to investigate effects of RUT against cisplatin‐induced reproductive toxicity in male rats. Twenty‐one adult male Sprague Dawley rats were used. The control group received physiological saline with oral gavage during 14 days, and physiological saline was injected intraperitoneally (IP) in 10th days of study. CP Group received physiological saline during 14 days, and 10 mg kg^?1 CP was injected IP in 10th day. RUT + CP group received RUT (150 mg kg^?1) during 14 days, and 10 mg kg^?1 CP was injected IP in 10th day. Spermatological parameters (including motility, cauda epididymal sperm density, dead sperm percentage and morphological sperm abnormalities), biochemical (MDA, GSH, GSH‐px, SOD and CAT), histological (H&E dye) and immunochemistry evaluations of testicles were evaluated. CP treatment caused damage on some spermatological parameters, increased the oxidative stress and induced testicular degeneration and apoptosis when compared to the control group. However, RUT treatment mitigates these side effects when compared to the CP alone group. IT is concluded that RUT treatment may reduce CP‐induced reproductive toxicity as a potential antioxidant compound.     

Dose‐dependent effects of ethanol extract of Salvia haematodes Wall roots on reproductive function and copulatory behaviour in male rats

This study was aimed to investigate the dose‐dependent effects of Salvia haematodes Wall roots (SHW) extract on male reproductive function and copulatory behaviour in rats. Sexually mature males were assigned to four groups: control and treated (5, 50 and 300 mg kg^?1 day^?1 for 30 days). At the end of treatment regimes, the reproductive activity viz. body/organ weights, testicular spermatogenesis, daily sperm production rate (DSP) and epididymal sperm counts, and sexual behaviour including mounting latency (ML), mounting frequency (MF), intromission latency (IL), intromission frequency (IF), ejaculation latency (EL), post‐ejaculatory interval (PEI) and penile reflexes (PE) were assessed. Results showed significant increase in body weight (at 300 mg kg^?1), testis/epididymis weights (at 50 and 300 mg kg^?1), testicular spermatids, DSP, tubular diameter and epididymal sperm counts (at 50 and 300 mg kg^?1doses) in treated compared with control rats. It also produced dose‐dependant changes in sexual behaviour. The 5 mg kg^?1 dose of extract increased MF and PE, whereas 50 and 300 kg^?1 doses caused significant increase in MF, IF, PE, EL (but less than sildenafil citrate treatment), hit rate and seminal plug weight. It is concluded that SHW extract enhances anabolic activity, testicular function and sexual behavioural performance in a dose‐dependant manner.     

Prostate‐specific targeting of the aqueous root extract of Croton membranaceus in experimental animals

Croton membranaceus Müll.Arg. (Euphorbiaceae) is used for benign prostate hyperplasia (BPH) treatment. The study aimed at investigating organs that the aqueous root extracts of C. membranaceus (CMARE) target, which is absent in literature. Twenty‐four male Sprague‐Dawley rats (100–140 g) were randomly divided into 4 groups. Group 1, the control group received distilled water. Groups 2, 3 and 4 received 30, 150 and 300 mg kg^?1 b.wt CMARE respectively (oral gavage). Rats fed 90 days the standard chow diet ad libitum. Upon sacrifice, major organs were histologically examined and serum prostate‐specific antigen (PSA) biochemically determined. Only the prostate was abnormal. Histologically, H&E staining revealed thickness and infoldings of the epithelial cells shrinking with increasing dose. The 30 mg kg^?1 group showed low columnar or flattened epithelium cells, whereas the columnar epithelium infoldings of the 150 mg kg^?1 b.wt and 300 mg kg^?1 b.wt groups were virtually nonexistent. The acini of the control, 30 mg kg^?1 b.wt group and the 150 mg kg^?1 b.wt groups showed clear pinkish secretion. However, secretion of the high‐dose group appeared light pink in colour and the stroma cells appeared much darker than all the treated and control group. C. membranaceus targets the prostate with significant PSA reduction (P < 0.01).     

Quercetin mitigates fenitrothion‐induced testicular toxicity in rats

Fenitrothion (FNT) is a widely used organophosphorus pesticide in agriculture. Quercetin (QR), a plant‐derived flavonoid, has a free radical scavenging property. This study investigated the protective effect of QR on FNT‐induced testicular toxicity in rats. Twenty‐four male rats were divided into four groups. Group I (control) received normal saline. Group II was administered QR at the dose of 50 mg kg^?1 b.wt. Group III was orally administered FNT (20 mg kg^?1 b.wt). Group IV was gavaged FNT and QR together at the same doses. All administrations were performed daily by gavage and maintained for 70 days. Sperm parameters and histopathological changes in testes were investigated. Serum testosterone and luteinising hormone were estimated using radioimmunoassay kits. In testes, expressions of steroidogenic genes (3β‐hydroxysteroid dehydrogenase type 6, 17 β‐hydroxysteroid dehydrogenase type 3 and steroidogenic factor‐1) and oxidative stress genes (catalase and superoxide dismutase) were determined using real‐time PCR. FNT administration caused significant decreases in sperm count, motility and hormonal levels, a significant increase in abnormal sperm morphology and a significant down‐regulation of steroidogenic and antioxidant genes in the testis. However, QR administration ameliorated FNT‐induced toxic effects. Our results concluded that QR effectively mitigated testicular damage induced by FNT in rats.     

Chemoprotective effects of kolaviron on ethylene glycol monoethyl ether‐induced pituitary‐thyroid axis toxicity in male rats

Endocrine disrupting chemicals cause reproductive dysfunction by interacting with intricate regulation and cellular processes involve in spermatogenesis. This study investigated the probable mechanism of action of ethylene glycol monoethyl ether (EGEE) as an antiandrogenic compound as well as the effects of kolaviron upon co‐administration with EGEE in rats. Adult male rats were exposed to EGEE (200 mg kg^?1 bw) separately or in combination with either kolaviron [100 (KV1) and 200 (KV2) mg kg^?1 bw] or vitamin E (50 mg kg^?1 bw) for 14 days. Western blot analysis revealed that the administration of EGEE adversely affected steroidogenesis in experimental rats by decreasing the expression of steroid acute regulatory (StAR) protein and androgen‐binding protein (ABP). EGEE significantly decreased the activities of 3β‐hydroxysteroid dehydrogenase (3β‐HSD) and 17β‐hydroxysteroid dehydrogenase (17β‐HSD) but markedly increased sialic acid concentration in rat testes. EGEE‐treated rats showed significant decreases in plasma levels of luteinising hormone (31%), testosterone (57.1%), prolactin (80.9%), triiodothyronine (65.3%) and thyroxine (41.4%), whereas follicle‐stimulating hormone was significantly elevated by 76.9% compared to the control. However, co‐administration of kolaviron or vitamin E significantly reversed the EGEE‐induced steroidogenic dysfunction in rats. This study suggests that kolaviron may prove promising as a chemoprotective agent against endocrine pathology resulting from EGEE exposure.     

Toxic effects of arsenic on semen and hormonal profile and their amelioration with vitamin E in Teddy goat bucks

The present environmental study has been planned to investigate the toxic effects of arsenic on reproductive functions of Teddy bucks as well as to examine whether these toxic effects are ameliorated by vitamin E. Sixteen adult Teddy bucks were divided randomly into four equal groups A, B, C and D with following treatment: A (control), B (sodium arsenite 5 mg kg^?1 BW day^?1), C (vit E 200 mg kg^?1 BW day^?1 + Arsenic 5 mg kg^?1 BW day^?1) and D (vit E 200 mg kg^?1 BW day^?1). This treatment was continued for 84 days. Semen quality parameters were evaluated weekly. Male testosterone, luteinising hormone (LH), follicle‐stimulating hormone (FSH) and cortisol levels were measured through enzyme‐linked immunosorbent assay (ELISA) after every 2 weeks. The data were subjected to two‐way analysis of variance followed by Duncan test for multiple comparisons. Semen evaluation parameters were reduced significantly (P < 0.05) in arsenic‐treated animals. The serum hormonal profile of testosterone, LH and FSH was reduced significantly (P < 0.05) in arsenic group, while the serum level of cortisol was increased. Vitamin E alleviated the toxic effects of arsenic on semen and hormonal parameters. It may be concluded from this study that sodium arsenite causes major toxicity changes in semen and hormonal profile in Teddy goat bucks and vitamin E has ameliorative effects on these toxic changes.     

Protective effects of udenafil citrate,piracetam and dexmedetomidine treatment on testicular torsion/detorsion‐induced ischaemia/reperfusion injury in rats

The aim of this study was to investigate the antioxidant properties of udenafil citrate (1.4 mg kg^?1–2.8 mg kg^?1), dexmedetomidine 25 μg kg^?1 and piracetam 200 mg kg^?1 administered on ipsilateral/contralateral testes after ischaemia in a rat model of testicular torsion/detorsion (T/D) and define its protective effect histologically. Fifty‐six Wistar albino rats were included and randomly assigned into 6 groups. No intervention was performed in control group (Group 1, n = 8) and in torsion/detorsion group, (Group 2, n = 8). Udenafil 1.4 mg kg^?1 was given to torsion/detorsion group (Group 3, n = 10), udenafil 2.8 mg kg^?1 was given to torsion/detorsion group (Group 4, n = 10), piracetam 200 mg kg^?1 was given to torsion/detorsion group (Group 5, n = 10) and dexmedetomidine 25 μg kg^?1 was given to torsion/detorsion group (Group 6, n = 10) intraperitoneally after 60 mins of testicular torsion. Biochemical and histopathological testicular injury were evaluated. When the tissue was examined by TOS values, Group 3, Group 4 and Group 5 were significantly lower than Group 2. In contrary Group 6 values were significantly higher than Group 2. The increasing doses of udenafil demonstrated antioxidant properties on the testis tissue and histopathological that protects the testicles.     

Reproductive and toxic effects of methanol extract of Alchornea cordifolia leaf in male rats

Alchornea cordifolia leaf is traditionally used for the treatment of venereal diseases and for the enhancement of fertility throughout its area of distribution in Africa. The effect of oral administration of the methanol extract of the leaf was evaluated on some reproductive and haematological parameters of male rats at 0 (control group), 100, 200, 400, 800 and 1600 mg kg^?1. The toxicity study revealed nonsignificant alterations (P > 0.05) in the values of total and differential white blood cell count, but the erythrocyte count, packed cell volume, haemoglobin concentration and haematometric indices were significantly decreased (P < 0.05) at 1600 mg kg^?1 dose. Markers of hepatic damage (aspartate aminotransferase and alanine aminotransferase) and renal damage (urea and creatinine) were significantly elevated (P < 0.05) at 800 and 1600 mg kg^?1. The bioactivity (reproductive) study revealed significant increases (P < 0.05) in testicular weight, sperm count and motility, and serum testosterone levels, at the 200 and 400 mg kg^?1. The study concludes that the extract of Alchornea cordifolia leaves has toxic potential at 800 mg kg^?1 and 1600 mg kg^?1 doses, but is safe and has beneficial effects on male reproduction when used at doses equal to or lower than 400 mg kg^?1.     

Role of endothelin receptors and relationship with nitric oxide synthase in impaired erectile response in diabetic rats

To evaluate the protective role of bosentan (BOS), an endothelin‐1 (ET‐1) receptor antagonist, and to show the changes in rats with experimentally induced diabetic erectile dysfunction (ED), a total of 24 albino Wistar rats were allocated into four groups. Group 1 was the healthy group and Group 2 had diabetes mellitus (DM) induced by intraperitoneal injection of 60 mg kg^?1 streptozotocin (STZ). Following the establishment of DM, Group 3 and Group 4 were treated with oral BOS doses of 50 mg kg^?1 and 100 mg kg^?1, respectively, for 60 days. At the end of the treatment, we evaluated yawning and erection response to apomorphine treatment and then the animals were sacrificed. ET‐1, eNOS, iNOS, tumour necrosis factor (TNF)‐α, ET‐RA and ET‐RB mRNA expressions were analysed in cavernosal tissue. It was observed that yawning and erection response decreased in the diabetic group; however, both of these improved with BOS treatment. While ET‐1, TNF‐α and iNOS gene expressions increased, eNOS, ET‐RA and ET‐RB gene expressions decreased in the DM group compared to the healthy group. DM has a negative impact on cavernosal tissue blood flow through activating vasoconstrictor mediators in cavernosal tissue. BOS regulates significantly eNOS, iNOS and TNF‐α expressions in a dose‐dependent manner.     

Cisplatin‐induced testicular dysfunction and its amelioration by Launaea taraxacifolia leaf extract

This study investigates the ameliorative potential of Launea taraxacifolia (LT) aqueous leaf extract on cisplatin‐induced testicular dysfunction in Wistar rats. Thirty rats were randomly divided into six groups (A–F) of 5 rats each: Group A which served as control received water; Group B was intraperitoneally (ip) injected 10 mg kg^?1 body wt cisplatin on day 21; Groups C and D were given 100 and 400 mg of LT via oral administration, respectively, for 21 days while Groups E and F received similar treatment as Groups C and D, respectively, and then exposed to ip administration of 10 mg kg^?1 body weight cisplatin on the 21st day. Exclusively, Cisplatin‐exposed Group B rats showed reduced sperm characteristics and increased sperm morphological abnormalities; distorted histological architecture of seminiferous tubules; significantly increased lipid peroxidation (LPO) and decreased activities of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH)levels in the testes. These parameters in LT alone treated Groups C and D were not markedly different compared with the control group. The rats with the combined treatment in Groups E and F showed significantly improved sperm parameters, testicular histo‐architecture and antioxidant enzymatic activities. Conclusively, aqueous extract of L. taraxacifolia has protective potential against cisplatin damage.     

Ameliorative effect of polydatin on oxidative stress‐mediated testicular damage by chronic arsenic exposure in rats

Arsenic causes lipid peroxidation leading to alterations in antioxidant status in organisms. In this study, the reproductive effects of chronic exposure to arsenic and the protective effects of polydatin (PD) were evaluated in 35 Wistar male rats, which were divided equally into five groups. The control group received a normal diet and tap water, arsenic (100 mg l^?1, approximately 1/50 of oral LD₅₀) was given via drinking water to experimental groups except control group, and PD was orally given to the other groups at dose of 50, 100 and 200 mg kg^?1 for 60 days. Arsenic administration decreased sperm motility, glutathione level, superoxide dismutase and catalase activities in testicular tissue of rats. In contrast, malondialdehyde level and DNA damage were found to be high levels in arsenic‐treated group. Histopathologically, it was observed that decreased sperm concentration and degeneration of Sertoli cells in testicular tissue. PD administration, partially 200 mg kg^?1, reversed arsenic‐induced lipid peroxidation, DNA damage, antioxidant enzyme activity and cell integrity in testis of rats. These results demonstrate that PD decreases arsenic‐induced lipid peroxidation, enhances the antioxidant defence mechanism and regenerates tissue damage in testis of rats.     

3,3 diindolylmethane leads to apoptosis,decreases sperm quality,affects blood estradiol 17 β and testosterone,oestrogen (α and β) and androgen receptor levels in the reproductive system in male rats

3,3 Diindolylmethane (DIM) is a major digestive product of indole‐3 carbinol, obtained from Brassica family vegetables such as broccoli, cabbage and Brussels sprouts. This study aimed to investigate the effects of DIM on sperm parameters, histological structures of testicular tissues, blood testosterone (T) and estradiol 17‐β (E2) in male rats. Thirty‐eight male Sprague Dawley rats were used. Rats were divided into four groups: Group I: referred as Control group, received corn oil only; Group II: as DIM‐10, rats received 10 mg kg^?1 DIM; Group III: as DIM‐50, rats received 50 mg kg^?1 DIM; Group IV: as DIM‐100, received 100 mg kg^?1 DIM during 53 days. Spermatological parameters, malondialdehyde (MDA) levels of testes and serum T and E2 levels were assayed. Histopathological examinations of tests were done. DIM caused an increase in MDA levels. It decreased motility and live sperm rates and increased degeneration of testicular tissues. While DIM‐10 did not affect abnormal sperm rate, higher concentrations increased the abnormalities. Sperm density was higher in DIM‐10 groups when compared to both other groups. Only DIM‐50 had an anti‐androgenic effect among all groups. Only, DIM‐10 showed anti‐estrogenic activity as compared to higher DIM groups. In conclusion, DIM (i) had side effect on some sperm characteristics, (ii) increased the MDA levels and (iii) led to histological degeneration of testicular tissues and apoptosis in a dose‐dependent manner.     

Effect of etodolac hydrazone,a new compound synthesised from etodolac,on spermatozoon quality,testicular lipid peroxidation,apoptosis and spermatozoon DNA integrity

The aim of this study was to investigate the effect of etodolac hydrazone (EH), a new compound synthesised from etodolac, on spermatozoon quality, testicular lipid peroxidation, apoptosis and spermatozoon DNA integrity in rats. Group 1 (n = 8) received 1 ml dimethyl sulfoxide (DMSO) daily (Control); group 2 (n = 8) was treated with 5 mg kg^?1 day^?1 EH, dissolved in 1 ml DMSO (EH‐5); and group 3 (n = 8) was treated with 10 mg kg^?1 day^?1 EH, dissolved in 1 ml DMSO (EH‐10). All administrations were performed by gavage and maintained for 8 weeks. Both doses of EH administration caused significant decreases in absolute and relative weights of testis, whole epididymis, right cauda epididymis, and spermatozoon motility, spermatozoon count in comparison with the control group. Only 10 mg kg^?1 day^?1 EH administration caused significant decreases in absolute and relative weights of seminal vesicles and serum testosterone level, and significant increases in testicular lipid peroxidation level, and numbers of TUNEL+ apoptotic germ cells and spermatozoa with damaged DNA along with some histopathological damages when compared to the control group. However, body and ventral prostate weight, and testicular antioxidant markers (glutathione, glutathione‐peroxidase and catalase), were unaffected significantly by both doses of EH administration. In conclusion, two different doses of EH, in particular its high dose, damage to testicular spermatogenic cells and spermatozoon DNA and, it decreases spermatozoon motility, count and testosterone level in healthy rats.     

Bioefficacy of hydromethanolic extract of tuber of Chlorophytum borivilianum (Safed Musli) for the management of male infertility in cyproterone acetate‐treated albino rats

Increase in male sexual dysfunction, and its treatment with conventional aphrodisiac drugs with side effects lead to investigate the spermatogenesis and androgenesis augmentative efficacy of hydromethanolic (40 : 60) extract of root of Chlorophytum borivilianum (family – Liliaceae) against cyproterone acetate‐induced subfertility in Wistar strain male albino rat. For this purpose, experimental rats were divided into three treatment groups: vehicle (received distilled water), cyproterone acetate (gastric intubation at 250 mg kg^?1 twice daily for 35 days) and cyproterone acetate plus root extract of C. borivilianum (gastric intubation at 250 mg kg^?1 plus 400 mg kg^?1 with an interval of 20 min twice daily for 35 days). After 35‐day treatment, all rats were euthanised. Reproductive deviations towards negative side were investigated by screening the spermatogenic and steroidogenic biosensors. Oxidative stress profile in reproductive organs and sperm pellet was evaluated by biochemical assessment of antioxidative enzyme activities and level of end products of the lipid peroxidation. Apoptosis profile was evaluated by Western blot study, TUNEL assay and DNA fragmentation study of testicular tissues. Evaluation of toxicity profile was included for experimental investigation. After cyproterone acetate treatment, the pituitary–testicular axis was deviated towards the negative side and its tuning system was affected by oxidative stress and apoptosis‐mediated process, which reduced the quality of semen and finally led to subfertility. Co‐administration of C. borivilianum root extract enhanced male reproductive potentiality and prevented the negative deviations after the treatment with cyproterone acetate by means of increasing oxidative defence and maintaining homeostasis in testicular apoptosis process.     

Quercetin exacerbates the effects of subacute treatment of atrazine on reproductive tissue antioxidant defence system,lipid peroxidation and sperm quality in rats

The study investigated the reproductive function and the antioxidant defence system of rats co‐exposed to atrazine [ATZ, 120 mg kg^?1 body weight (b. wt)] and quercetin (QT, 20 mg kg^?1 b. wt.). ATZ had no significant effects on feed intake, body weights and reproductive organs weight except prostate weight. Sperm abnormalities were increased, whereas sperm production, sperm motility and epididymal and testicular sperm numbers were decreased with ATZ treatment. Antioxidant enzymes including superoxide dismutase, glutathione‐S‐transferase and glutathione peroxidase were significantly altered in the epididymis and testis resulting to lipid peroxidation. A potentiating response on glutathione‐S‐transferase and aspartate aminotransferase activities in the testis and on lactate dehydrogenase activity and glutathione level in the epididymis was observed in the QT + ATZ animals. Quercetin alone decreased seminal vesicle and prostate weights, increased superoxide dismutase activity in the testis and ascorbate level in the epididymis. Mild pathological changes were observed in the ATZ group, whereas considerable necrosis of seminiferous tubular cells with hypoplasia of the epithelia was observed in the QT + ATZ animals. The epididymis of these animals had multilayered and sometimes a single lining epididymal epithelium with few spermatozoa. We conclude that quercetin at the investigated dose increases the susceptibility of rat reproductive tissues to atrazine‐induced oxidative damage.     

Sperm abnormalities induced by pre‐pubertal exposure to cyclophosphamide are effectively mitigated by Moringa oleifera leaf extract

Moringa oleifera L. is a medicinal plant with potential antioxidant property. This study was aimed at investigating the chemoprotective effect of Moringa oleifera leaf extract (MOE) on cyclophosphamide (CP)‐induced testicular toxicity. Two‐week‐old male Swiss albino mice were intraperitoneally injected with phosphate‐buffered saline, 50 mg kg^?1 of CP and 25 mg kg^?1 of MOE. In combination treatment, mice were injected with 25 mg kg^?1 of MOE 24 h prior to CP injection, 24 h prior and post‐CP injection and 24 h post‐CP injection for 5 consecutive days (10 mg kg^?1). Six weeks later, mice were sacrificed to assess epididymal sperm parameters. MOE alone did not have any significant effect on sperm parameters. However, acute injection of CP resulted in significant decline in motility (P < 0.001), increase in head abnormality (P < 0.01) and DNA damage (P < 0.05). Combining MOE with CP increased the sperm density, motility and reduced head defect and DNA damage, irrespective of the schedule and dosage of MOE. Administration of MOE prior to CP significantly elevated the level of superoxide dismutase and catalase with concomitant decrease in lipid peroxidation in the testicular tissue. In conclusion, MOE may have potential benefit in reducing the loss of male gonadal function following chemotherapy.     

Effectiveness of cinnamon (Cinnamomum zeylanicum) bark oil in the prevention of carbon tetrachloride‐induced damages on the male reproductive system

In this study, it was aimed to investigate the likelihood of detrimental effects of carbon tetrachloride (CCl₄) on male reproductive system through oxidative stress mechanism and also protective effects of cinnamon bark oil (CBO). For this purpose, 28 healthy male Wistar rats were divided into four groups, seven rats in each. Group 1 received only olive oil daily; group 2 was treated with 100 mg kg^?1 CBO daily; group 3 was treated with only 0.25 ml kg^?1 CCl₄ weekly; and group 4 received weekly CCl₄ + daily CBO. All administrations were made by intragastric catheter and maintained for 10 weeks. Body and reproductive organ weights, sperm characteristics, testicular oxidative stress markers and testicular apoptosis were examined. CCl₄ administration caused significant decreases in body and reproductive organ weights, testicular catalase (CAT) activity, sperm motility and concentration, and significant increases in lipid peroxidation (LPO) level, abnormal sperm rate and apoptotic index along with some histopathological damages compared with the control group. However, significant improvements were observed in absolute weights of testis and epididymis, all sperm quality parameters, LPO level, apoptotic index and testicular histopathological structure following the administration of CCl₄ together with CBO when compared to group given CCl₄ only. The findings of this study clearly suggest that CBO has protective effect against damages in male reproductive organs and cells induced by CCl₄.     

Therapeutic effects of date palm (Phoenix dactylifera L.) pollen extract on cadmium‐induced testicular toxicity

Cadmium (Cd) is a well‐known testicular toxicant. This study was designed to explore the long‐term effects of a single low dose of Cd on spermatogenesis, and testicular dysfunction and oxidative stress, and the therapeutic potential of date palm pollen extract (DPP) in averting such reproductive damage. Adult male Wistar rats received a single intraperitoneal injection of CdCl₂ (0 or 1 mg kg^?1). Twenty‐four hours later, they started receiving DPP (0 or 40 mg kg^?1) orally, once daily for 56 consecutive days. Cd exposure caused significant reproductive damage via reduced weight of the reproductive organs, which includes spermatological damage (decreased sperm count and motility and increased rates of sperm abnormalities), increased oxidative stress (increased malondialdehyde and decreased reduced glutathione levels), histological alterations (necrosis, inefficient to completely arrest spermatogenesis and a reduced Johnsen's score) and decreased serum testosterone level. DPP restored spermatogenesis and attenuated the toxic effects of Cd on the reproductive system to the levels observed in the control animals. These findings support the hypothesis that the testis is particularly sensitive to Cd, which can cause testicular damage and infertility. Treatment with DPP can ameliorate the deleterious effects of Cd, probably by activating testicular endocrine and antioxidant systems.     

Effects of montelukast and zileuton on testicular torsion/detorsion injury in rats

The aim of this study was to evaluate and compare the effects of 5‐lipoxygenase enzyme (5‐LO) inhibitor zileuton and cysteinyl leukotriene receptor (CysLT1R) antagonist montelukast in testicular torsion/detorsion (T/D) injury model in rats. Rats were anaesthetised with 75 mg kg^?1 ketamine hydrochloride and 8 mg kg^?1 xylazine intraperitoneal before the operation. Torsion was created by rotating the right testis 720° clockwise and maintained by fixing the testis. The rats were treated with CysLT1R antagonist montelukast (10 mg kg^?1; i.p.), 5‐LO inhibitor zileuton (3 mg kg^?1; i.p.), and vehicle, at 30 min prior detorsion. After 1 h of torsion, the testis was counter‐rotated to the natural position and replaced into the scrotum. Malondialdehyde (MDA) level was measured in testicular tissue after 3 h of reperfusion. Histological examination was performed after 24 h of reperfusion. T/D caused a significant increase in MDA level and histopathological injury in testes. Montelukast and zileuton treatments prevented the T/D‐induced augmentation in MDA levels. Only zileuton treatment significantly reduced the T/D‐induced histopathological injury. In this study, we demonstrated for the first time that zileuton had protective effects on testicular T/D injury. We have also found that zileuton is more effective than montelukast on histopathological injury.     

Strontium fructose 1, 6‐diphosphate alleviate cyclophosphamide‐induced oligozoospermia by improving antioxidant and inhibiting testicular apoptosis via FAS/FASL pathway

This study investigated the treatment effects of a new compound, strontium fructose 1, 6‐diphosphate (FDP‐Sr), in cyclophosphamide (CP)‐induced oligozoospermia. FDP‐Sr, with extra high‐energy supply, could reverse male hypogonadism in the testis. Male Wistar rats were randomly divided into three groups: control group (vehicle treated), CP group and CP + FDP‐Sr group. Both CP group and CP + FDP‐Sr groups were orally administered CP (20 mg kg^?1) consecutively for the first 7 days to establish CP‐induced testicular toxic models. Subsequently, CP group was given orally distilled water per day, whereas CP + FDP‐Sr group was received FDP‐Sr (200 mg kg^?1) for 49 days. Compared to the CP group, the FDP‐Sr group showed significantly increased levels of serum testosterone, testis relative weights and epididymal sperm counts in rats. In addition, rats treated by FDP‐Sr showed the recuperative activities of testicular marker enzymes and normalised levels of antioxidants in tissue. Testicular protection of FDP‐Sr was further demonstrated by enhancing expression of P450scc, reducing ability of FAS/FASL and generating cytoprotection in the histopathological study. FDP‐Sr appeared to possess an ability to attenuate CP‐induced reproduction toxicity via the activation of antioxidants and steroidogenesis enzymes, and alleviate oligozoospermia via inhibition of testicular apoptosis by FAS/FASL pathway.