Testicular Toxicity In Male Rats Research Articles

Molecular insights into the antioxidative and anti-inflammatory effects of P-coumaric acid against bisphenol A-induced testicular injury: In vivo and in silico studies

This study investigated the protective effects of p-coumaric acid (PCA) against bisphenol A (BPA)-induced testicular toxicity in male rats. The rats were divided into control, BPA, BPA+PCA50, BPA+PCA100, and PCA100 groups. Following a 14-day treatment period, various analyses were conducted on epididymal sperm quality and testicular tissues. PCA exhibited dose-dependent cytoprotective, antioxidant, and anti-inflammatory effects, ameliorating the decline in sperm quality induced by BPA. The treatment elevated antioxidant enzyme activities (SOD, GPx, CAT) and restored redox homeostasis by increasing cellular glutathione (GSH) and reducing malondialdehyde (MDA) levels. PCA also mitigated BPA-induced proinflammatory responses while reinstating anti-inflammatory IL-10 levels. Apoptotic parameters (p53 and p38-MAPK) were normalized by PCA in BPA-treated testicular tissue. Immunohistochemical and immunofluorescent analyses confirmed the cytoprotective and anti-inflammatory effects of PCA, evidenced by the upregulation of HO-1, Bcl-2, and Nrf-2 and the downregulation of the proapoptotic gene Bax in BPA-induced testicular intoxication. PCA corrected the disturbance in male reproductive hormone levels and reinstated testosterone biosynthetic capacity after BPA-induced testicular insult. In silico analyses suggested PCA's potential modulation of the oxidative stress KEAP1/NRF2/ARE pathway, affirming BPA's inhibitory impact on P450scc. This study elucidates BPA's molecular disruption of testosterone biosynthesis and highlights PCA's therapeutic potential in mitigating BPA's adverse effects on testicular function, showcasing its cytoprotective, anti-inflammatory, and hormone-regulating properties. The integrated in vivo and in silico approach offers a comprehensive understanding of complex mechanisms, paving the way for future research in reproductive health and toxicology, and underscores the importance of employing BPA-free plastic wares in semen handling.

Attenuating potential of some antioxidants: Cellgevity, max one, purslane and vitamin C on caffeine induced hormonal and testicular toxicities in male albino rats

Background: Infertility challenges in men, resulting from disturbances in hormonal balance and testicular integrity, stands as a significant health challenge associated with various factors. Consequently, diverse strategies are necessary to tackle this issue. This research explored the attenuating potentials of some antioxidants—Cellgevity (CG), Max One (MX), purslane, and vitamin C (VC)—on caffeine-induced hormonal and testicular toxicities in male albino rats. Methodology: Sixty sexually matured male albino rats were randomly divided into ten groups consisting of two rats in three replicates using completely randomized design (CRD). Group one served as control and received water and feed only. Group two were given 200 mg/kgBw of CG, group three received 200 mg/kgBW of MX, group four received 100 mg/kgBW of VC, group five received 200 mg/kgBW of caffeine, group six received 200mg/kgBW of purslane, group seven received 200 mg/kgBW of caffeine and 200 mg/kgBW of CG, group eight received 200 mg/kgBW of caffeine and 200 mg/kgBW of MX, group nine received 200mg/kgBW of caffeine and 200 mg/kgBW of purslane, group ten received 200 mg/kgBW of caffeine and 100 mg/kgBW of VC. Administration was done orally and lasted for 65days. The rats were sacrificed after administration using chloroform anaesthesia. The testes were processed for histology while blood sample were obtained for hormonal assay. Results: The results showed that caffeine significantly (p<0.05) reduced the serum levels of testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol when compared to the control and other treatments groups. There was testicular toxicity with loosely packed enlarged seminiferous tubules in caffeine treated animals when compared with the control and antioxidants treated animals. However, CG, MX, purslane and VC attenuated the effect of caffeine in all the parameters evaluated by increasing the levels of the hormones and restoring testicular integrity of the animals in the combination groups. Conclusion: This present study has revealed the toxic effect of caffeine reproductive hormones and testicular integrity of male albino rats. However, the findings of this study provided substantial evidence on the attenuating effects of CG MX, purslane and VC on caffeine-induced hormonal and testicular toxicity in male rats as mammalian models.

Comparing the effects of Cyperus esculentus hydroethanolic extract and Euterpe oleracea on reproductive efficacy against cadmium-induced testicular toxicity in male rats.

Cadmium chloride (CdCl2) is an environmentally toxic pollutant that can cause reprotoxicity. Cyperus esculentus and Euterpe oleracea are potent antioxidant plants currently used to counteract the action of harmful pollutants. The present experiment was intended to evaluate and comp are the role of C. esculentus hydroethanolic extract (CHE) and E. oleracea in treating the reprotoxicity induced by CdCl2 in rats. Forty adult male rats (160-210 gm) were allocated into five groups equally. Control group: received 5 ml of normal saline (NS); the other treatment groups were injected with CdCl2 as a single dose for two weeks to induce testicular toxicity. After 14 days, the four groups were treated orally daily for two months as follows: The cadmium group (Cd) received NS, the third group (TC) was administered 800 mg/kg BW of CHE, the fourth group (TO) received 500 mg/kg BW of E. oleracea, and the fifth group (TCO) received CHE with E. oleracea. The live sperm and motility, serum testosterone, follicle-stimulating hormone (FSH), testicular superoxide dismutase (SOD), catalase (CAT), steroidogenic acute regulatory protein (StAR), 17β-hydroxysteroid dehydrogenase, and 3β-hydroxysteroid dehydrogenase (3β-HSD) were significantly increased in the TCO, TC, and TO groups compared with the Cd group. Testicular nitric oxide and malondialdehyde were elevated significantly in the Cd group compared to the TC, TO, TCO, and control groups. The fold changes of Fshβ, Lhβ, and Gnrh genes were upregulated in the TCO group compared to the Cd and control groups. The combination of CHE with E. oleracea showed improvements in rat testicles affected by cadmium toxicity via upregulated reproductive gene expression and its antioxidant effects.

Sciadopitysin mitigates spermatological and testicular damage instigated by paraquat administration in male albino rats

Paraquat (PQ) is a herbicide that has ability to induce testicular toxicity by producing reactive oxygen species (ROS). Sciadopitysin (SPS) is a promising flavonoid that displays multiple pharmacological properties i.e., anti-inflammatory, anti-oxidant and anti-apoptotic. Therefore, the present study was designed to evaluate the mitigative role of SPS against PQ induced testicular toxicity in male rats. The experiment was performed on male albino rats (n = 48) that were divided into 4 groups. The group-1 was control group. Group-2 was administrated orally with PQ (5 mg/kg). Group-3 was administrated orally with PQ (5 mg/kg) and SPS (2 mg/kg). Group-4 was supplemented with SPS (2 mg/kg) through oral gavage. The experiment was conducted for 56 days. The exposure to PQ significantly lowered the activities of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD) as well as glutathione peroxidase (GPx). Whereas, a substantial increase was observed in dead sperms number, abnormalities in the tail, head as well as midpiece of sperms in PQ intoxicated rats. Moreover, a significant increase in the level of ROS and malondialdehyde (MDA) was noticed in PQ administrated group. Furthermore, steroidogenic enzymes expression was significantly decreased in PQ-intoxicated group, whereas the level of inflammatory markers was increased in PQ administrated rats. Besides, the expression of apoptotic markers was significantly escalated in PQ exposed rats, whereas the expression of anti-apoptotic markers was considerably reduced. A significant reduction in hormonal level was also noticed in the rats that were administrated with PQ. Moreover, the histopathological examination revealed that PQ significantly damaged the testicles. However, the supplementation of SPS with PQ significantly reduced the adverse effects of PQ in the testes of albino rats. Therefore, the current investigation demonstrated that SPS possesses a significant potential to avert PQ-induced testicular dysfunction due to its anti-apoptotic, androgenic, anti-oxidant and anti-inflammatory nature.

Protective Effect of L-Carnitine against Deltamethrin Induced Male Reproductive Toxicity in Adult Rats Exposed at their Prepubertal Stage

The present study aims to investigate the protective role of L-Carnitine (LC) against Deltamethrin-induced testicular toxicity in male rats exposed during their early developmental period. DTM was administered at a dose of 6 mg/kg body weight to the prepubertal rat’s Post-Natal Day (PND) 23 rats through oral route and exposure was continued until they reach PND 90. After completion of the exposure period, male rats were assessed for reproductive endpoints. Deltamethrin exposure caused a significant reduction in testosterone production and decreased the sperm parameters such as sperm count, sperm motility, sperm viability and sperm membrane integrity. Deltamethrin intoxication also reduced the reproductive organs’ weight and testicular steroidogenic enzymes (3β-hydroxysteriod dehydrogenase and 17β-hydroxysteriod dehydrogenase) levels. Further DTM exposure induced the oxidative stress as evidenced by the significant reduction in the superoxide dismutase, catalase, and glutathione levels with significant elevation in the malondialdehyde. DTM also induced the significant sperm DNA damage. In addition, DTM exposure significantly declined the testosterone levels over the control group, indicating the impaired steroidogenesis. In addition to the compromised steroidogenesis DTM exposure also deteriorated the testicular architecture according to the histological observations. On the other hand, therapy with LC (100 mg/kg body weight) improved the biomass of reproductive organs, the features of the sperm, testicular steroidogenesis and testicular antioxidant enzymes levels. Concluding that DTM might disturb the testicular antioxidant level that eventually impaired the reproductive health of rats. However, LC supplementation mitigated the reproductive toxicity through its antioxidant property.

Ameliorative effect of selenium nanoparticles on testicular toxicity induced by cisplatin in adult male rats.

Cisplatin (Cis) is a treatment for testicular germ-cell tumors (TGCTs). Unfortunately, it causes testicular toxicity due to releasing reactive oxygen species (ROS) causing damage to testicular cells and chromosomes. The current study aimed to investigate the ameliorative effect of selenium nanoparticles (SeNPs) against cisplatin testicular toxicity in male rats by assessment of body weight, testis weight, oxidative stress markers in testis homogenates as (malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione reduced (GSH), Glutathione peroxidase (GSH∼PX) and Catalase (CAT)), gene expression, testosterone concentration (T), sperm characteristics (count, motility and abnormality) and testicular histopathology. Methods: Thirty adult male rats divided equally into four groups; a single dose intraperitoneally injection of cisplatin (10mg/kg) and selenium nanoparticles (2mg/kg/day) were administrated alone or in combination. Cis group showed a decrease in body weight, testis weight, antioxidant activities (SOD, GSH, GSH∼PX and CAT), T concentration and steroidogenetic expression, the data recorded an increase in MDA levels and sperm abnormality, meanwhile histopathology of testis sections showed degenerative changes in the seminiferous tubules. The co-administration of selenium nanoparticles ameliorated the harmful effects of cisplatin. In conclusion; SeNPs through its antioxidant potential may be useful to prevent the testicular toxicity induced by cisplatin to the rat testis by reducing oxidative stress.

Appraisal of the Pre-Emptive Effect of Lactoferrin Against Chromium-Induced Testicular Toxicity in Male Rats

Lactoferrin (LCF), a potent naturally occurring antioxidant, is a crucial component in preventing potassium dichromate (PDC) toxicity. The goal of the current work was to study the potential efficacy of LCF in preventing PDC(CrVI)-induced testicular toxicity and oxidative injury in rats. Six groups of male rats of Wistar stain were randomly categorized into: group 1, which served as the control; group 2 and 3 received LCF (200 and 300 mg/kg orally, respectively); group 4 received PDC (2 mg/kg i.p.); group 5 and 6 pretreated with LCF, followed by PDC as in group 4 with 90 min apart for 28 days. PDC-intoxicated rats showed a significantly altered spermogram with abnormal sperm morphology. PDC significantly upregulated serum FSH and downregulated testosterone levels. Additionally, PDC decreased the levels of testicular key antioxidant biomarkers (catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH)) with elevated lipid peroxidation marker (TBARS) and testicular chromium content. Moreover, it upregulated testicular proinflammatory cytokines, IL-1, IL-6, IL-10, and TNF-α, induced histopathological changes in testes with significant immunohistochemical expression of FasL and moderate expression of Nrf2. Pretreatment with LCF significantly mitigated PDC-induced testicular toxicity by enhancing spermogram, improving hormonal levels, restoring testicular oxidant/antioxidant balance, and decreasing testicular IL-1, IL6, IL-10, and TNFα levels, and amending both FasL and Nrf2 immunohistochemical-expression. Additionally, LCF improved testicular histopathological picture and spermatogenesis. Our results highlight the importance of LCF as a superior protective modulator of PDC-induced testicular injury.

Antioxidant, anti-inflammatory, and anti-reprotoxic effects of kaempferol and vitamin E on lead acetate-induced testicular toxicity in male rats.

The heavy metals cause repro-toxicity via oxidative stress and suppress the antioxidant enzymes. Kaempferol and vitamin E possess antioxidant properties that can counteract the deleterious heavy metals effects. The present study was directed to investigate the protective role of kaempferol, alone or with vitamin E, on testicular toxicity mediated by lead acetate in male rats. Fifty adult male rats were randomly grouped into five groups (n = 10): the control group received 5 ml distilled water, and the Pb group was intraperitoneally injected with 20 mg/kg of lead acetate. The Pb + Vitamin E group received Pb with 100 mg/kg of vitamin E, the Pb + KAF group received Pb with 50 mg/kg of kaempferol, the Pb + KAF + Vitamin E group received Pb with kaempferol and vitamin E for 6 weeks. The testicular levels of superoxide dismutase, catalase, steroidogenic enzyme, serum testosterone, follicle-stimulating hormone, interleukin (IL)-10, and sperm function were significantly decreased in the Pb group compared with all experimental groups. These parameters were significantly elevated in the Pb + KAF + Vitamin E group compared to other experimental groups. Lead acetate caused elevation in testicular malondialdehyde, nitric oxide, IL-6, IL-1β, tumor necrosis factor-α, nuclear factor kappa, and sperm abnormality compared to all treatment groups. All these parameters were significantly declined in the Pb + KAF + Vitamin E group and Pb + KAF group compared with the Pb group. The fold changes of pituitary follicle-stimulating hormone beta, gonadotropin-releasing hormone receptor, and luteinizing hormone beta, and testicular CYP11A1, LH receptor, and FHr gene expression were significantly upregulated in Pb + KAF + Vitamin E group compared with all experimental groups. In addition, KAF + Vitamin E has the potential to improve testicular regeneration in seminiferous tubules, Leydig, and Sertoli cells. Administration of kaempferol alone or with vitamin E can mitigate lead acetate-induced testicular toxicity in rats via its antioxidant and anti-inflammatory properties. The current research is the first to demonstrate that kaempferol can exert a preventive role in testicular dysfunction.

Hydrogen sulfide alleviates acrylamide-induced testicular toxicity in male rats

Hydrogen sulfide alleviates acrylamide-induced testicular toxicity in male rats

Efficacy of Carnosine administration along with or without Coenzyme Q10 on sodium valproate induced testicular toxicity in vivo models

Background and aimIn the present study, the effect of carnosine along with or without Coenzyme Q10 was tested on the sodium valporate induced testicular toxicity in male rats. Methods: The five different treatments were designed and its biological, relative weight of reproductive organs, serum lipid profiles, reproductive hormones levels and sperm motility factors were evaluated to provide a possible alternative to meet the problem of infertility in males. Results: the experimental rats showed a significant decrease in body weight gain and no difference was recorded feed intake and feed efficiency ratio in different treatments. The treatment of Carnosine along with CoQ10 does not produce any significant change in the relative weight of prostate in SVA induced rats. Further, the SVA induced male rats treated with the combination of Carnosine and CoQ10 showed significant decrease in total cholesterol, triglycerides and a significant increase in HDL-c, LDL-C, VLDL-C levels as compared to control. The same treatment resulted in the significant improvement in the reproductive hormones like testosterone, FSH and LH levels in the serum. Also, the biochemical parameters such as SOD, GST, GPX and catalase levels increased and decreased MDA serum antioxidant level when treated with both Carnosine and CoQ10. Conclusions: The combination of Carnosine and CoQ10 showed a succeeding increase in sperm motility even after 6 h of sperm storage. Thus, the obtained results from current study proved that the carnosine along with CoQ10 may be best alternative solution to treat male infertility.

Effects of Quercetin against Doxorubicin-Induced Testicular Toxicity in Male Rats

Effects of Quercetin against Doxorubicin-Induced Testicular Toxicity in Male Rats

Chitosan/Selenium Nanoparticles Attenuate Diclofenac Sodium-Induced Testicular Toxicity in Male Rats

The detrimental effect of diclofenac sodium (Diclo-Na) on male reproductive organs is reported upon in this paper. Chitosan is a polysaccharide composed of various amounts of glucosamine. Chitosan nanoparticles (CH-NPs) have attracted much attention owing to their biomedical activity. Selenium (Se) has a vital role in nutrition, plays an important role in enhancing male reproduction, and has a wide range of free radical scavenging activities. However, the study of the impact of chitosan nanoparticles in combination with Se (IV) (CH-NPs/Se) on male reproductive toxicity associated with Diclo-Na administration is lacking in recent literature. The current study assessed the ameliorative effects of complexes of CH-NPs/Se (IV) on Diclo-Na and the ways in which they alter reproductive toxicity in male rats. Male rats were treated for 30 days successively, either with Diclo-Na (10 mg/kg) or co-treated with a CH-NPs/Se complex (280 mg/kg). Sperm characteristics, marker enzymes of testicular function, LH, FSH, and testosterone were evaluated in addition to oxidative stress markers and histological alterations. CH-NPs/Se significantly alleviated Diclo-Na-induced decline in sperm count and motility, testicular function enzymes, and levels of LH and testosterone in serum. Additionally, CH-NPs/Se co-administration at 280 mg/Kg, inhibited the Diclo-Na-induced decline of antioxidant enzyme activities and elevated oxidative stress indices and reactive free radicals in testicular homogenates of male rats. CH-NPs/Se (280 mg/kg) alone improved Diclo-Na and ameliorated histological damages in exposed rats. In conclusion, chitosan improved testicular function in Diclo-Na-treated rats by enhancing the testosterone hormone levels, ameliorating testicular tissue, and inhibiting markers of oxidative stress in male rats.

L-carnitine modulates autophagy, oxidative stress and inflammation in trazodone induced testicular toxicity

BackgroundTrazadone is an antidepressant and may affect reproductive hormones and spermatogenesis. l-carnitine is an amino acid that exhibits antioxidant actions. This study was designed to investigate the potential protective effects of l-carnitine against trazadone-induced testicular toxicity in male rats and the possible underlying mechanisms such as oxidative stress, inflammation and autophagy. Methodsthirty-two male Wistar rats were divided randomly into four equal groups (n = 8). Testicular damage was induced by oral administration of Trazadone (TRZ, 20 mg/kg/day, p.o.) for four weeks (TRZ group). l-carnitine (LC, 200 mg/kg/day, p.o.) was applied for four weeks (LC group). LC + TRZ group administered the same doses of LC and TRZ concomitantly. The control group received distilled water (as vehicle). Resultsthe protective treatment with LC attenuated the decline of sperm count and motility resulted from trazadone administration. Moreover, LC ameliorated trazadone increased lipid peroxidation (MDA) and reduction of total thiol and catalase activity. LC modulated the elevation in tumor necrosis factor- α (TNF-α), and increased the expression of autophagy related genes Becline-1, ATG 5 and ATG-12 in rat testes. Serum level of FSH, LH and total testosterone were increased significantly (p < 0.001) in LC + TRZ group. Histopathological findings further supported the protective effects of LC against trazadone -induced testicular injury by increasing free sperms within the lumen of spermatogenic cells and improving testicular degeneration. ConclusionThese findings supported the protective effects of l-carnitine on rat testes due to suppression of oxidative stress, inflammation and enhancing autophagy. l-carnitine may be recommended as adjuvant therapy to trazadone treatment.

The antioxidant and anti-apoptotic potential of Pleurotus eryngii extract and its chitosan-loaded nanoparticles against doxorubicin-induced testicular toxicity in male rats.

This study was conducted to evaluate the protective role of Pleurotus eryngii extract (PE) and Pleurotus eryngii extract-loaded chitosan nanoparticles (PE-CSNP) against doxorubicin (DOX)-induced testicular toxicity in rats. Male rats were divided into six groups: control (DMSO/ethanol), PE (200mg/kg PE), PE-CSNP (30mg/kg PE-CSNP), DOX (10mg/kg DOX, a single dose, i.p), DOX+PE (10mg/kg DOX+200mg/kg PE) and DOX+PE-CSNP (10mg/kg DOX+30mg/kg PE-CSNP). PE and PE-CSNP were administered by oral gavage every other day for 21days. DOX-treated rats showed histopathological impairment compared with the control group. There was an increase in the apoptotic index, caspase 3 (CASP3), BCL2-associated X apoptosis regulator (BAX), dynamin-related protein 1 (DRP1) expression and total oxidative status (TOS) in the DOX group, while mitofusin-2 (MFN2), total antioxidative status (TAS) and serum testosterone levels of the DOX group reduced when compared with the other groups. PE and PE-CSNP treatments provided significant protection against DOX-induced oxidative stress by reducing TOS levels and increasing TAS levels. CASP3, BAX, apoptotic index and DRP1-MFN2 expressions were restored by PE and PE-CSNP. However, the PE-CSNP showed higher antioxidant and anti-apoptotic efficacy compared with PE. Thus, our results provide evidence that CSNP and PE could synergistically have a potent antioxidant and anti-apoptotic therapy against DOX-induced testicular damage in male rats.

Nutritional supplementation of D-Ribose-L-Cysteine suppresses oxidative stress, spermatogenesis and steroidogenesis recovery in rats exposed to mercury chloride: histomorphometry and biochemical evidence

BackgroundMercury chloride (HgCl2) is known to cause reproductive dysfunction. The negative effects may be ameliorated with the use of certain antioxidants. Present study focused on impact of D-Ribose-L-Cysteine (DRLC) on mercury chloride-induced testicular toxicity in male rats. Materials and methodsForty-eight (48) adult male Sprague-Dawley rats weighing 150-200g randomized into six groups of eight (n=8) rats each. Group A treated with 1mg/Kg body weight (bwt) HgCl2; Group B received 30mg/Kg bwt of DRLC; Group C received 1mg/Kg bwt of HgCl2 and 30 mg/Kg bwt of DRLC; Group D received 1mg/Kg bwt of HgCl2 and 30mg/Kg bwt of Vit. C; Group E received 1mg/Kg bwt of HgCl2 and 30mg/Kg bwt of DRLC and 30 mg/Kg bwt of Vit. C; Group F served as control given normal saline orally for 8 weeks. Testicular histology, histomorphometry parameters, and other parameters such as sperm, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (TT), reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) were investigated. ResultsAdministration of HgCl2 disorganized seminiferous epithelium and widened the hypocellular interstitium; significantly decrease the sperm quality, TT, FSH, LH, CAT, GPx, GSH, SOD, and increases the MDA compared to control group. Co-administration of HgCl2, DRLC and Vit.C decrease the MDA and increase hormonal and antioxidant level; improved sperm quality and restored testicular histopathological alterations. ConclusionIntervening action of DRLC therefore, resulted in normal germinal cell layers, suppresses oxidative stress, spermatogenesis and steroidogenesis recovery in HgCl2 induced testicular toxicity.

The Possible Protective Effects of Coenzyme Q10 on Malathion-induced Testicular Toxicity in Male Rats

The Possible Protective Effects of Coenzyme Q10 on Malathion-induced Testicular Toxicity in Male Rats

Ethyl acetate fraction of Spathodea campanulata (Bignoniaceae) attenuates lead acetate induced testicular toxicity in male Wistar rats.

The use of Spathodea campanulata in folklore medicine for the management of reproductive disorders has been poorly reported. We sought to investigate the protective potential of the ethyl acetate fraction of S.campanulata stem bark extract (EFSC) on lead acetate-induced (LA) testicular toxicity in male rats. Animals during a 28days treatment received dimethyl sulfoxide (DMSO, 0.1%), LA (20mg/kg), and EFSC (200mg/kg). Others received EFSC only (100, 200, and 400mg/kg) or vitamin E (100mg/kg) 1h prior to LA (20mg/kg) administration. LA administration decreased sperm counts and motility by 36.39 and 40.69% respectively in rats. Also, LA-untreated rats showed elevated malondialdehyde (MDA) and decreased total proteins in testis (260, 33%) and epididymis (62, 29%) respectively. However, EFSC (100, 200, or 400mg/kg) administrations improved sperm morphological characteristics as well as antioxidant status in LA-treated rats. EFSC (400mg/kg) showed improved testis seminiferous tubules that were almost normal in the LA-treated rats. Further, EFSC contains a high 9-octadecenoic acid methyl ester. Overall, evidence by LA-induced testicular toxicity, EFSC provides chemopreventive roles via antioxidant mechanisms.

Roflumilast protects from cisplatin-induced testicular toxicity in male rats and enhances its cytotoxicity in prostate cancer cell line. Role of NF-κB-p65, cAMP/PKA and Nrf2/HO-1, NQO1 signaling

Cisplatin (CIS)-induced testicular injury is a major obstacle in its application as antineoplastic agent. In this study, we investigated the protective effect and mechanism of roflumilast (ROF), a PDE4 inhibitor, against CIS-induced testicular toxicity in rats. Besides, the cytotoxic effect of CIS, with and without ROF, was evaluated on PC3 cell line. ROF reversed CIS-induced abnormalities in sperm characteristics, normalized serum testosterone level, and ameliorated CIS-induced alterations in testicular and epidydimal weights and restored normal testicular structure. Moreover, ROF increased intracellular cAMP level, PKA and HO-1 activities and Nrf2, NQO-1 and HO-1 gene expression, improved testicular oxidative stress parameters (TBARS, NO, GSH levels, and CAT activity) and inflammatory mediators (IL-1β and TNF-α, and NF-κβ p65gene expression) and reduced the proapoptotic proteins, caspase-3, Bax and increased Bcl-2. Lastly, in vitro analyses showed that ROF augmented the anticancer efficacy of CIS and enhanced the increase in gene expression of Nrf2, HO-1, and NQO-1 and the inhibition of gene expression of NF-κβ p65 induced by CIS and enhanced its apoptotic effect in PC3 cells. Conclusively, PDE4 inhibition with induction of Nrf2/HO-1, NQO-1 is a potential therapeutic approach to protect male reproductive system from the detrimental effects with augmenting, the antineoplastic effect of CIS.

Phytochemical and Biological Evaluation of a Newly Designed Nutraceutical Self-Nanoemulsifying Self-Nanosuspension for Protection and Treatment of Cisplatin Induced Testicular Toxicity in Male Rats.

The incorporation of cisplatin (CP) as a cytotoxic antineoplastic agent in most chemotherapeutic protocols is a challenge due to its toxic effect on testicular tissues. Natural compounds present a promising trend in research, so a new nutraceutical formulation (NCF) was designed to diminish CP spermatotoxicity. A combination of three nutraceutical materials, 250 mg Spirulina platensis powder (SP), 25 mg Tribulus terrestris L. extract (TT), and 100 mg fish oil (FO) were formulated in self-nanoemulsifying self-nanosuspension (SNESNS). SP was loaded into the optimized self-nanoemulsifying system (30% FO, 50% span 80/cremophor EL and 20% isopropanol) and mixed with TT aqueous solution to form SNESNS. For the SP, phytochemical profiling revealed the presence of valuable amounts of fatty acids (FAs), amino acids, flavonoids, polyphenols, vitamins, and minerals. Transmission electron microscopy (TEM) and particle size analysis confirmed the formation of nanoemulsion-based nanosuspension upon dilution. Method validation of the phytochemical constituents in NCF has been developed. Furthermore, NCF was biologically evaluated on male Wistar rats and revealed the improvement of spermatozoa, histopathological features, and biochemical markers over the CP and each ingredient group. Our findings suggest the potential of NCF with SNESNS as a delivery system against CP-induced testicular toxicity in male rats.

Development of health-based environmental screening levels for insensitive munitions constituents

Dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ) are constituents of insensitive munitions being developed to minimize the acute hazards associated with non-intentional detonation of warheads. Although a reference dose (RfD) has been established for NQ and occupational exposure levels have been developed for all three compounds, current state-of-the science methods were not used. Here we present the latest toxicity data and interpretations for NTO, DNAN, and NQ and use Bayesian Benchmark Dose modeling and a Bayesian approach to applying uncertainty factors to derive tolerable daily intake (TDI) values. A TDI of 0.02 mg/kg-d was calculated for DNAN based on extramedullary hematopoiesis in female rats. A TDI of 2.4 mg/kg-d was derived for NTO based on testicular toxicity in male rats. A TDI of 4.0 mg/kg-d was derived for NQ based on increased fetal resorptions in rabbits. These TDIs are generally an order of magnitude higher than previously developed reference values. These values can be used to inform public health, occupational safety, and product acquisition and stewardship decisions. Drinking water, soil, and tap water screening levels were derived for residential and worker exposure scenarios to help inform risk assessment decisions.