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Background: Diesel particulate matter (DPM) induces several adverse effects on humans upon exposure. Objectives: In this study, we looked into the impact of DPM exposure on testicular toxicity brought on by cyclophosphamide in mice including spermatogenesis and oxidative damage. Results: The CP treatment reduces testicular weight and sperm motility and increases sperm abnormalities, such as amorphous head formation. Histopathological examination of CP-treated mouse testes revealed various morphological alterations in the testis, including an increased incidence of exfoliation of spermatogenic cells, degeneration of early spermatogenic cells, vacuolation of Sertoli cells, and a decreased number of spermatogonia/spermatocytes/spermatids, along with a high number of apoptotic cells. Moreover, the testes exhibited reduced glutathione (GSH) levels and catalase activity, and also increased malondialdehyde concentration. Meanwhile, DPM exposure exacerbated the testicular histopathological alterations induced by CP. The DPM exposure also aggravated oxidative damage by decreasing GSH levels in the testis. Conclusion: These results suggest that DPM exposure exacerbates CP-induced testicular toxicity in mice, which might be attributable to the reduced antioxidant activity. [ABSTRACT FROM AUTHOR]

Background: 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. Aim: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

The current study was designed to evaluate the aphrodisiac properties of Craterispemum schweinfurthi leaf extract in lead induced testicular toxicity in male Wistar rats using appropriate standard techniques. Adult male Wistar rats were divided into 7 groups and daily treated with different concentrations of extract and phytosterol only. Compared to group 1 (Control) rats, significantly higher values of mount, intromission, ejaculatory latencies as well as post ejaculatory interval and decreased values of mount, intromission and ejaculatory frequencies were observed amongst group 2 (2.25mg/kg Lead only) rats (p

Objective(s): In the present study, it was evaluated whether morin has a protective effect on testicular toxicity caused by ifosfamide (IFOS), which is used in the treatment of various malignancies. Materials and Methods: For this purpose, 100 or 200 mg/kg morin was given to Sprague Dawley rats for 2 days, and a single dose (500 mg/kg) IFOS was administered on the 2nd day. At the 24th hr of IFOS administration, animals were decapitated and testicular tissues were taken and the status of oxidative stress, inflammation, endoplasmic reticulum stress (ERS), autophagy, and apoptosis markers were analyzed by biochemical, molecular, and histopathological methods.Results: According to the data obtained, it was determined that IFOS caused oxidative stress in testicular tissues. It was observed that inflammation, ERS, autophagy, apoptosis, and oxidative DNA damage occurred with oxidative stress. Morin treatment suppressed oxidative stress. Morin showed anti-inflammatory effects by reducing TNF-α and IL-1β protein levels. It also increased the mRNA transcript levels of the ERS marker ATF-6, PERK, IRE1, GRP-78, and CHOP genes, and the apoptosis marker genes Bax, Casp-3, and apaf-1. It up-regulated the anti-apoptotic protein Bcl-2 gene and the cell survival signal AKT-2 gene. Morin caused a decrease in beclin-1 protein levels and showed an anti-autophagic effect. In addition, morin attenuated oxidative DNA damage and decreased 8-OHdG immune-positive cell numbers.Conclusion: As a result, it was observed that IFOS caused cellular damage by activating various signaling pathways in testicular tissue, while morin exhibited protective properties against this damage.

Abstract Background The clinical use of sildenafil citrate (Viagra), a drug used to treat erectile dysfunction, is limited because of its many side effects on tissues. In this context, we aimed to investigate the protective effects of hesperidin, a citrus flavonoid, on hepatic and testicular damage induced by a high dose of sildenafil citrate in male rats. Rats were randomly divided into four groups. The first group was used as the control group. The second group was orally administered sildenafil citrate at a high dose of 75 mg/kg thrice a week. In the third group, hesperidin was administered orally at a dose of 50 mg/kg/day. The fourth group was administered 75 mg/kg sildenafil citrate three times a week with 50 mg/kg hesperidin daily. The experiment lasted for 28 days. Results In the sildenafil-treated groups, blood indices were altered, liver function tests were deranged, and serum testosterone levels were reduced. In the liver and testicular tissue, sildenafil citrate treatment resulted in significant reductions in catalase and total antioxidant capacity; as well as increased malondialdehyde, reactive oxygen species, and nitrous oxide levels. In addition, sildenafil citrate treatment caused abnormal histopathological patterns in both the liver and the testes. Liver vascular endothelial growth factor and testicular steroidogenic acute regulatory protein gene expression were upregulated. Conclusions Hesperidin attenuated the harmful effects of intensive sildenafil citrate treatment on liver and testicular functions, alleviated oxidative stress and normalized blood indices. Therefore, hesperidin could be protective against sildenafil citrate-induced oxidative damage that may develop over the long term.

The reproductive system of males is adversely impacted by lead (Pb), a toxic heavy metal. The present study examined arbutin, a promising hydroquinone glycoside, for its potential ameliorative impact against Pb-induced testicular impairment in rats. The testicular injury was induced by the intraperitoneal administration of Pb acetate (20 mg/kg/day) for 10 consecutive days. Thirty-six rats were divided into six experimental groups (n = 6 per group): control, control treated with oral arbutin (250 mg/kg), control treated with intraperitoneal arbutin (75 mg/kg), untreated Pb, Pb treated with oral arbutin, and Pb treated with intraperitoneal arbutin. The treatments were administered daily for 10 days. Arbutin was administered by the oral and intraperitoneal routes to compare the efficacy of both routes in mitigating Pb acetate-induced testicular dysfunction. The current data revealed that both oral and intraperitoneal administration of arbutin significantly enhanced serum testosterone and sperm count/motility, indicating the amelioration of testicular dysfunction. In tandem, both routes lowered testicular histopathological aberrations and Johnsen’s damage scores. These favorable outcomes were driven by dampening testicular oxidative stress, evidenced by lowered lipid peroxidation and increased glutathione and catalase antioxidants. Moreover, arbutin lowered testicular p-JAK2 and p-STAT3 levels, confirming the inhibition of the JAK2/STAT3 pro-inflammatory pathway. In tandem, arbutin suppressed the testicular NLRP3/caspase-1/NF-B axis and augmented the cytoprotective PK2/PKR2 pathway. Notably, intraperitoneal arbutin at a lower dose prompted a more pronounced mitigation of Pb-induced testicular dysfunction compared to oral administration. In conclusion, arbutin ameliorates Pb-evoked testicular damage by stimulating testicular antioxidants and the PK2/PKR2 pathway and inhibiting the JAK2/STAT3 and NLRP3/caspase-1 pro-inflammatory pathways. Hence, arbutin may be used as an adjunct agent for mitigating Pb-induced testicular impairment.

Continuous exposure to nanoparticles (NPs) poses potential hazards to human health and animal life, necessitating thorough monitoring and investigation of environmental contaminants to mitigate their adverse effects. Therefore, this study investigates the histopathological alterations, serum biochemistry, oxidative stress biomarkers, and genotoxicity endpoints induced by crystalline silica (C-SiO2) NPs, sliver-silica (Ag-SiO2) and zinc-oxide silica (ZnO-SiO2) NPs in Rattus Norvegicus. Twenty-five rats were blindly distributed into groups (A, B, C, & D), with B, C, and D administered 500 µg/kg of ZnO-SiO2, Ag-SiO2, and C-SiO2 NPs intravenously (IV), while A served as the control. Severe histopathological alterations, including widening of urinary spaces, edema, necrosis of neurons, atrophy of neurons, myofibrillolysis, inflammatory exudate, disorganization of splenic cells, and pyknotic nuclei, were observed in C-SiO2 NPs-exposed rats across study organs. Compared to controls, C-SiO2 NPs significantly altered 95 % of serological, DNA damage, histopathological, and oxidative stress parameters. Ag-SiO2 and ZnO-SiO2 NPs affected 75 % and 60 % of these parameters, respectively. Among the NPs, C-SiO2 exhibited the most adverse effects. The study concludes that SiO2 coating on metal (Ag) and metal oxide (ZnO) rendered these substances biocompatible, suggesting potential applications for reducing adverse effects in living organisms. These findings also contribute to the genotoxic profiling of NPs and their potential health hazards upon exposure to humans.

Polyethylene microplastics (PE-MPs) are one of the environmental contaminants that instigate oxidative stress (OS) in various organs of the body, including testes. Kaempferide (KFD) is a plant-derived natural flavonol with potential neuroprotective, hepatoprotective, anti-cancer, anti-oxidant and anti-inflammatory properties. Therefore, the present study was designed to evaluate the alleviative effects of KFD against PE-MPs-prompted testicular toxicity in rats. Fourty eight adult male albino rats were randomly distributed into 4 groups: control, PE-MPs-administered (1.5 mgkg-1), PE-MPs (1.5 mgkg-1) + KFD (20 mgkg-1) co-treated and KFD (20 mgkg-1) only treated group. PE-MPs intoxication significantly (P

Objective: To observe the histomorphological changes in rat testes treated with Fluoxetine, focusing on the weight of the testis along with the epithelial thickness of the seminiferous tubules and evaluating the ameliorative effects of Moringa oleifera on the same gross and histological parameters. Study Design: Laboratory-based experimental study. Place and Duration of Study: Army Medical College, National University of Medical Sciences (NUMS), with the National Institute of Health, Islamabad and Pak Emirates Military Hospital, Rawalpindi Pakistan, from Sep 2022 to Mar 2023. Methodology: Thirty male Sprague Dawley rats divided into three groups (n=10). Group-A was the Control-Group, and the rest served as the Experimental-Group. Drugs were given in a single daily dose through oral gavage for eight weeks. Group-B was given Fluoxetine, 10 mg/kg body weight. Group-C was administered Fluoxetine in the same dose and concomitant administration of Moringa powder, 50mg/30 grams body weight. After sacrifice, testes were fixed and stained with Hematoxylin and Eosin for histological study. Results: The study found a statistically significant decrease in the weight of rat testis (p-value˂0.05) and epithelial thickness of seminiferous tubules of rats treated with Fluoxetine (p-value ˂0.05). Conclusion: Fluoxetine significantly decreased the weight of the testis and epithelial thickness of the seminiferous tubules in rat testes. Moringa Oleifera administration ameliorated these effects in the short term.

Increased life expectancy turns the public into aged societies, and aged individuals are expected to reach 2 billion of the world’s population. Aging is a time accumulating decline in the body's biological function. An important aging hallmark is epigenetic alteration. Tea is a rich source of Epigallocatechin Gallate which has a role in aging epigenetics modulation. This review is conducted to clarify and derive a more precise description of the association between Epigallocatechin Gallate (EGCG) and epigenetic alteration as an aging hallmark. The search was conducted in four databases (PubMed, Science Direct, Scopus, and Google Scholar) for peer-reviewed articles published between January 2011 and December 2020. Studies were selected according to the association between EGCG and regulation of aging-related epigenetic marks in mice animal models following the PRISMA statement checklist. The role of EGCG in muscle aging is the modification of miRNA, which decreases gene expression and proteins responsible for muscle wasting, another role of EGCG in aging through increasing AcH3K9 and HDAC1 lower expression, which improves cardiac diastolic function. EGCG is one of the epigenetics modifying phytochemicals in aging; according to the aging theory, histone acetylation restoration by HDAC 1 inhibitors, and there is a (geromiRNAs) regulating aging-associated genes activity. [ABSTRACT FROM AUTHOR]

Objective(s): In the present study, it was evaluated whether morin has a protective effect on testicular toxicity caused by ifosfamide (IFOS), which is used in the treatment of various malignancies. Materials and Methods: For this purpose, 100 or 200 mg/kg morin was given to Sprague Dawley rats for 2 days, and a single dose (500 mg/kg) IFOS was administered on the 2nd day. At the 24th hr of IFOS administration, animals were decapitated and testicular tissues were taken and the status of oxidative stress, inflammation, endoplasmic reticulum stress (ERS), autophagy, and apoptosis markers were analyzed by biochemical, molecular, and histopathological methods. Results: According to the data obtained, it was determined that IFOS caused oxidative stress in testicular tissues. It was observed that inflammation, ERS, autophagy, apoptosis, and oxidative DNA damage occurred with oxidative stress. Morin treatment suppressed oxidative stress. Morin showed anti-inflammatory effects by reducing TNF-α and IL-1β protein levels. It also increased the mRNA transcript levels of the ERS marker ATF-6, PERK, IRE1, GRP-78, and CHOP genes, and the apoptosis marker genes Bax, Casp-3, and apaf-1. It up-regulated the anti-apoptotic protein Bcl-2 gene and the cell survival signal AKT-2 gene. Morin caused a decrease in beclin-1 protein levels and showed an anti-autophagic effect. In addition, morin attenuated oxidative DNA damage and decreased 8-OHdG immune-positive cell numbers. Conclusion: As a result, it was observed that IFOS caused cellular damage by activating various signaling pathways in testicular tissue, while morin exhibited protective properties against this damage. [ABSTRACT FROM AUTHOR]

Background: The clinical use of sildenafil citrate (Viagra), a drug used to treat erectile dysfunction, is limited because of its many side effects on tissues. In this context, we aimed to investigate the protective effects of hesperidin, a citrus flavonoid, on hepatic and testicular damage induced by a high dose of sildenafil citrate in male rats. Rats were randomly divided into four groups. The first group was used as the control group. The second group was orally administered sildenafil citrate at a high dose of 75 mg/kg thrice a week. In the third group, hesperidin was administered orally at a dose of 50 mg/kg/day. The fourth group was administered 75 mg/kg sildenafil citrate three times a week with 50 mg/kg hesperidin daily. The experiment lasted for 28 days. Results: In the sildenafil-treated groups, blood indices were altered, liver function tests were deranged, and serum testosterone levels were reduced. In the liver and testicular tissue, sildenafil citrate treatment resulted in significant reductions in catalase and total antioxidant capacity; as well as increased malondialdehyde, reactive oxygen species, and nitrous oxide levels. In addition, sildenafil citrate treatment caused abnormal histopathological patterns in both the liver and the testes. Liver vascular endothelial growth factor and testicular steroidogenic acute regulatory protein gene expression were upregulated. Conclusions: Hesperidin attenuated the harmful effects of intensive sildenafil citrate treatment on liver and testicular functions, alleviated oxidative stress and normalized blood indices. Therefore, hesperidin could be protective against sildenafil citrate-induced oxidative damage that may develop over the long term. [ABSTRACT FROM AUTHOR]

Lead (Pb)-induced reprotoxicity is a detrimental consequence of Pb exposure, which results in abnormal spermatogenesis, testicular degeneration, and pathogenic sperm changes. The association between impaired male reproductive function and Pb-induced oxidative stress (OS) has been demonstrated, with consequent testicular antioxidant deficiency. The current study investigated the protective role of the natural antioxidant hesperidin (HSD) against lead-acetate (PbAc)-induced testicular toxicity. Male Wistar rats (n = 40) were randomly divided into four experimental groups: Group I (negative control) received 2.0 mL/kg BW 0.9% saline; Group II received 100 mg/kg BW PbAc; Group III received 100 mg/kg BW HSD; and Group IV received HSD two hours before PbAc using the abovementioned doses. The treatments were administered daily for 30 consecutive days. The results showed that HSD treatment significantly restored PbAc-induced decrease in body, epididymal, and testicular weights as well as in semen parameters, reproductive hormones, and testicular markers of OS. Reduced MDA levels and improved testicular histopathological findings were also observed. Collectively, this study sheds light on the preventive role of HSD against PbAc-induced testicular injury, which is mediated via the suppression of OS and the modulation of reproductive hormones as well as the plausibility of HSD being used as a supplementary therapeutic option for recovery. [ABSTRACT FROM AUTHOR]

Background: This study aims to study the histomorphological response of d-ribose-l-cysteine (DRLC) to ketamine-induced testicular damage in adult male Wistar rats. Methods: A total of 20 adult male Wistar rats were used for this experiment. The animals were randomly divided into four groups (A–D) (n = 5). Group A served as the control, receiving distilled water as placebo; animals in group B were administered with 50 mg/kg body weight (bw) of ketamine only; animals in group C were administered with 50 mg/kg bw of ketamine and 30 mg/kg bw of DRLC; animals in group D were administered with 30 mg/kg bw of DRLC only. At the end of the experiment, blood was taken from the heart via cardiac puncture and stored, semen was collected from the caudal epididymis for immediate sperm analysis, while the testes were excised and preserved for histological examination and biochemical analysis. Results: The results showed abnormalities marked by a significant decrease in the weights, sperm parameters, as well as antioxidants, serum hormonal levels and abnormal testicular microarchitecture in the rats as a result of ketamine treatment. However, DRLC exhibits significant quenching effects and attenuating activities on the ketamine-induced abnormalities by increasing the rats' weights, restoring the sperm parameters, as well as increasing the antioxidants and serum hormonal levels with restored testicular histoarchitecture. Conclusion: DRLC in the current study attenuated the toxic effects of ketam ine on the testes; therefore, it could be used as adjuvant therapy for reproductive toxicant-induced testicular toxicity due to its potent antioxidant property. Significance statement The testis is a vital secreting organ that produces and stores spermatozoa and is crucial for producing male sexual hormones and is thus the main target of infertility when overdoses of chemicals and toxins are introduced to it. In view of the facts above, studies of the potential of chemicals like ketamine to induce testicular toxicity are important as well as the methods aimed at mitigating this effect. Various stu dies have been conducted on the effectiveness of DRLC in subsiding different chronic health conditions, but there is no published literature on the effects of DRLC in ketamine-induced testicular toxicity in adult male Wistar rats. Hence we present this study.

The reprioritization of healthcare services occurred with the discovery of the highly contagious coronavirus 2 (SARS-CoV-2) in late 2019. Pharmacies played a crucial role in the healthcare system during the pandemic, contributing to the enhancement of patient care in all dimensions. This study aimed to evaluate the provision of community pharmacy services and the level of preparation exhibited during the COVID-19 pandemic in Saudi Arabia. Between July and November 2020, a cross-sectional study was conducted in Saudi Arabia. The study involved the distribution of a validated questionnaire to community pharmacists using electronic means. The questionnaire encompassed many issues aimed at evaluating the extent of preventative efforts, public knowledge, and the ramifications of the pandemic on the services provided by pharmacists. A total of 315 pharmacists from various regions around the country were included in this study. A significant proportion of individuals (81.9%) participated in educational programs focusing on COVID-19, with compulsory attendance required for 56.6% of these individuals. The most often implemented preventative measures in pharmacies were disinfecting clients' hands, wearing face masks, and checking body temperature, with respective application rates of 90.8%, 89.2%, and 85.1%. Moreover, most participants concurred that the provision of pharmaceutical counseling and public education saw the most significant impact due to the COVID-19 pandemic, with 52.1% and 49.5%, respectively. The report demonstrates a notable degree of compliance among community pharmacies concerning implementing preventative measures during the COVID-19 outbreak. Nevertheless, most of these preventative steps were implemented voluntarily and were tailored to individual needs and circumstances. [ABSTRACT FROM AUTHOR]

Arsenic (As) is a highly toxic metalloid. Carvacrol (CAR) is the active ingredient of Lamiaceae plants and has various biological and pharmacological properties. The present study investigated the protective effects of carvacrol (CAR) against testicular toxicity induced by sodium arsenite (SA). Rats were given SA (10 mg/kg) and/or CAR (25 or 50 mg/kg) for 14 days. Semen analyzes showed that CAR increased sperm motility and decreased the percentage of abnormal and dead sperm. It was determined that the oxidative stress induced by SA decreased with the increase of Nrf‐2 and HO‐1 expressions, SOD, CAT, GPx, and GSH levels, and MDA levels decreased after CAR treatment. It was observed that autophagy and inflammation triggered by SA in testicular tissue were alleviated by suppressing the expressions of LC3A, LC3B, MAPK‐14, NF‐κB, TNF‐α, IL‐1β, iNOS, and COX‐2 biomarkers in rats given CAR. Also, CAR treatment suppressed SA‐induced apoptosis by inhibiting Bax and Caspase‐3 expressions in testicles and up‐regulating Bcl‐2 expression. Histopathological analyzes showed that rats given SA had deterioration in tubule structure and spermatogenesis cell line, especially a serious loss of spermatogonia cells, atrophy of seminiferous tubules, and deterioration of germinal epithelium. In the group given CAR, the germinal epithelium and connective tissue were in normal morphological structure and an increase in seminiferous tubule diameters was observed. As a result, it was determined that oxidative stress, inflammation, autophagy, and apoptosis induced by SA were suppressed by CAR, thus protecting the testicular tissue from damage and increasing semen quality. [ABSTRACT FROM AUTHOR]

Exposure to Lead ‐causes testicular dysfunction through oxidative stress, inflammation, and apoptosis; however, naringenin (NGN) therapeutic impact against lead‐evoked testicular dysfunction remains elusive. Herein, the point of the study was to examine the defensive impact of NGN on testicular dysfunction initiated by lead. Seventy‐Two male Wistar rats were allotted into nine groups; control group, drug control groups, lead acetate group, as well as NGN treated groups (10, 25, and 50 mg/kg) respectively, given 5 days before lead acetate treatment. The result showed clearly the impact of lead on reduced sperm count, sperm motility as well as serum testosterone and LH levels. Additionally, it caused a significant rise in testicular inflammatory markers TNF‐α, IL‐1β, and TGFβ, effects that were accompanied by a reduction of AKT and mTOR levels. Lead acetate also caused degenerative changes in the testis, atrophy, and loss of spermatogenic series. Our findings revealed that NGN in a dose‐dependent manner improved spermiotoxicity induced by lead acetate via restoration of the testicular function, preservation of spermatogenesis, halting inflammatory cytokines along with the enhancement of germ cell survival using upregulation of AKT/mTOR expressions. The present study discloses that NGN suppresses lead acetate toxicity that is involved in the antioxidant effect in a dose‐dependent manner, besides its anti‐inflammatory property. [ABSTRACT FROM AUTHOR]

Objective: To assess the potential of plantain-based diet in modulating testicular toxicities in rats exposed to atrazine. Methods: The plantain-based diet at 50%, 25% and 12.5% were prepared from the basal diet by substituting the corn starch with plantain fruit pulp flour at different percentages. Wistar rats were fed plantain-based diet in varying concentrations ranging from 12.5% to 50% of the basal diet for 21 days before or after atrazine treatment in a two-phase experiment: preventive and therapeutic phases. The therapeutic model (n=35) had seven groups with 5 rats each, including the control, atrazine, atrazine recovery, atrazine plus plantain-based diet 50%, 25%, 12.5%, and atrazine plus quercetin groups. The preventive model (n=30) had six groups of 5 rats, consisting of the control, atrazine, 50%, 25%, 12.5% plantain-based diet plus atrazine, and quercetin plus atrazine groups. Gonadal hormones (testosterone, luteinizing hormone and follicle-stimulating hormone), sperm parameters (sperm motility, viability, morphology and concentration), and testicular function indices (protein, cholesterol, glycogen, acid phosphatase, alkaline phosphatase and lactate dehydrogenase) were measured. Results: The gonadal hormones, sperm characteristics, and testicular function indices of the rat testis decreased significantly in the atrazine group alongside degeneration of the histoarchitecture. However, plantain-based diet restored the gonadal hormone concentrations, semen parameters, and testicular function indices in both the preventive and therapeutic models. Conclusions: Treatment with plantain-based diet protects against rat testicular toxicity caused by atrazine via the modulation of gonadal hormones, sperm quality, testicular function index as well as histoarchitecture of rat testes.

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.

Objective: To investigate the protective role of pumpkin seed ethanolic extract against escitalopram-induced reproductive toxicity in male mice. Methods: Swiss albino male mice were randomly divided into five groups with six mice in each group. Group I received normal water orally, Group II, III, IV and V received escitalopram oxalate (10 mg/kg), pumpkin seed extract (300 mg/kg) plus escitalopram oxalate (10 mg/kg), escitalopram oxalate (20 mg/kg), and pumpkin seed extract (300 mg/kg) plus escitalopram oxalate (20 mg/kg), respectively. All test doses were continuously administered orally once daily per animal body weight for 30 days and 60 days. Body weight and sexual organ weight were evaluated on day 31 and 61. Effects of pumpkin seed extract on sperm parameters, biochemical parameters and histology of testis were also investigated. Results: Escitalopram 10 or 20 mg/kg caused reproductive toxicity in male mice after 30 and 60 days of treatment. However, simultaneous administration of escitalopram oxalate (10 or 20 mg/kg) with pumpkin seed extract (300 mg/kg) attenuated escitalopram-induced testicular toxicity. Significant increase in the body weight and relative organ weight was observed. Sperm count, sperm motility and viability significantly increased (P

Rèsumè Contexte Le bisphénol A (BPA) est l’un des produits chimiques synthétiques les plus utilisés dans le monde. Le BPA en tant que perturbateur endocrinien affecte le système reproducteur par le biais de ses propriétés œstrogéniques et anti-androgènes. Le resvératrol (RES), en tant que polyphénol naturel et puissant antioxydant, présente des effets protecteurs contre la toxicité sur la reproduction en inhibant le stress oxydatif. Quarante-huit rats mâles ont été divisés en huit groupes (n = 6), comprenant les groupes TÉMOIN, HUILE D’OLIVE (0,5 ml/jour), méthylcellulose Carboxyle (MCC) (1 ml de 10 g/L), RES (100 mg/kg/ jour), faible dose de 25 de BPA (25 mg/kg/jour), dose élevée de BPA (50 mg/kg/jour), faible dose de BPA + RES et dose élevée de BPA + RES. Tous les traitements ont été effectués quotidiennement par voie orale pendant 56 jours. À la fin de la 8ème semaine, des échantillons de sang ont été prélevés pour dosages hormonaux. Ensuite, les paramètres du sperme ont été analysés et le testicule gauche a été retiré pour une étude stéréologique. Résultats Nous avons montré une diminution significative des paramètres spermatiques dans les groupes traités par doses faibles et doses élevées de BPA par rapport aux groupe témoin (P

Chemotherapy is considered to be the most effective intervention in cancer treatment. The first use of chemotherapy began in the 1940s, unfortunately, its use result in many serious and debilitating side effects which affect human daily activities. Doxorubicin is a powerful antineoplastic drug FDA approved for the management of variety of cancer types including leukemia and lymphoma. however, its clinical use is limited due to its toxic effect to different tissues including testicular toxicity which has bad impact on quality of life to cancer survivors. DOX –induced testicular toxicity is accompanied by defects in sperm analysis including low sperm count, low sperm motility and high sperm abnormalities in addition to affecting on steroidogenesis. This review is intended to discuss the pharmacodynamics and the pharmacokinetics of doxorubicin, beside the possible underlying mechanisms may be contributed to damage of testicles caused by DOX including oxidative stress, inflammation, apoptosis and autophagy. moreover, the assessment of post – chemotherapy testicular toxicity in animals and the promising pharmacological treatment that has been studied in animal models were discussed.

Background Methotrexate (MTX) is a commonly used chemotherapeutic drug that has adverse toxic effects on germ cells. Naringin (NG) is a natural flavanone glycoside, with different phytotherapeutic applications, and its possible protective effects against MTX-induced testicular tissue damage were investigated in this study.Methods Low and high doses of NG (40 and 80 mg/kg/day) were given for 10 days by intraperitoneal (i.p.) injection and MTX (20 mg/kg i.p.) was given at the 4th day of the experiment, with or without NG in rats.Results The obtained results showed that exposure to MTX increased malondialdehyde (MDA) levels and nitric oxide (NO) production compared with the control. In the meantime, MTX depleted catalse (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), and reduced glutathione (GSH) in the testicular tissue. Further, serum testosterone levels were significantly decreased in the MTX group. NG significantly counteracted the aforementioned effects of MTX; however, NG80 was more effective in restoring SOD, GR, MDA and NO. Interestingly, NG80 achieved a better improvement in the ultrastructural pattern of the testicular cells in MTX-exposed rats.Conclusion These results indicated, for the first time, that NG could be a potential candidate therapy against MTX-reprotoxic impacts.

Objectives This study aimed to evaluate the potential mitigating effect of fisetin on monosodium glutamate (MSG)-induced testicular toxicity and investigate the possible involvement of silent mating type information regulation 2 homolog 1 (SIRT1) in this effect.Methods Forty male rats were divided into normal control, fisetin-treated, MSG-treated, and fisetin + MSG-treated groups. Testosterone, GnRH, FSH, and LH were measured in plasma, as well as SIRT1 and phosphorylated AMP-activated protein kinase (pAMPK) levels in testicular tissues using ELISA. Hydrogen peroxide (H2O2), nitric oxide (NO), and reduced glutathione (GSH) were measured colorimetrically, while Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) expression was relatively quantified using RT–PCR in testicular tissues.Results After 30 days, fisetin could ameliorate MSG-induced testicular toxicity by acting centrally on the hypothalamic-pituitary-gonadal axis, increasing plasma levels of GnRH, FSH, LH, and testosterone. Peripheral actions of fisetin on the testis were indicated as it increased testicular SIRT1 and pAMPK. Furthermore, it antagonized glutamate-induced oxidative stress by significantly lowering H2O2, NO, and relative NOX4 expression while significantly increasing reduced GSH levels. It also improved the architecture of the seminiferous tubules, reduced sperm abnormality, and increased sperm count.Discussion Fisetin ameliorates MSG-induced testicular toxicity via central and peripheral mechanisms making it a promising therapeutic target for male infertility.

Di-2-ethylhexyl phthalate (DEHP) is an extensively used plasticizer which has raised some concerns about its safety on human health. This study aimed at evaluating the effects of vanillic acid (VA) and vitamin C (VC) supplementation on DEHP-induced testicular toxicity. Thirty-five adult male Wistar rats were randomly divided into 7 groups (A–G) (n = 5) receiving distilled water; 250 mg/kg bw of DEHP only; 30 mg/kg bw of VA and 250 mg/kg bw of DEHP; 30 mg/kg bw of VC and 250 mg/kg bw of DEHP; 30 mg/kg bw of DEHP plus 30 mg/kg bw of VA and 30 mg/kg bw of VC; 30 mg/kg bw of VA only; and 30 mg/kg bw of VC only, respectively. At the end of the experiment, blood was taken from the heart via cardiac puncture and stored, semen was collected from the caudal epididymis for immediate sperm analysis, while the testes were excised and preserved for histological examination and biochemical analysis. The results showed a significant decrease (P < 0.05) in body weights, sperm motility, sperm volume, sperm viability and count, antioxidant levels, and reproductive hormonal levels, with a significant increase (P < 0.05) in sperm morphological defect and lipid peroxidation level in DEHP-only group compared with the control but was ameliorated after VA and VC administration compared to the DEHP-only treated animals. VA and VC supplementation attenuated the toxic effects of DEHP on the testicular functions, morphology, and semen characterization of the experimental adult male Wistar rats.

Occupational exposure to potentially harmful substances is one of the dangers associated with industrial jobs. This study evaluated the modulatory influence of selected dietary polyphenols on the pulmonotoxic and testiculotoxic effects of crude acetylene, an industrial gas used in welding metals. Wistar rats were exposed to 58 000 ppm acetylene, 20 min daily for 30 days, in a 36 L glass inhalation chamber. Some acetylene-exposed animals were treated concurrently with 30 mg/kg quercetin, rutin, caffeic acid, ferulic acid, or coumaric acid. At the end of the treatment sessions, the levels of superoxide dismutase, reduced glutathione, glutathione peroxidase, lactate dehydrogenase, and hormonal markers in rats exposed to acetylene were significantly decreased, with a concomitant increase in lipid peroxidation, nitric oxide level, cholesterol concentration, and histopathological abnormalities. These damaging biochemical and histopathological changes were significantly ameliorated in animals administered the polyphenols. Quercetin showed greater ameliorative activity than rutin while the phenolic acids exhibited increasing levels of ameliorative activity in the order: caffeic acid > ferulic acid > coumaric acid. These results indicate that inhalation of crude acetylene is deleterious to the lungs and testes, and polyphenols provide protection against these detrimental effects. [ABSTRACT FROM AUTHOR]

Di(n‐butyl) phthalate (DBP) is considered a substance of serious concern because of its reproductive toxicity and endocrine‐disrupting properties. Exposure to DBP causes morphological and functional changes in the male reproductive system of birds and mammals. However, there are no detailed reports on the effects of DBP on the Sertoli cell and junctional complexes of the blood–testis barrier (BTB) in birds. The present study investigated dose‐related ultrastructural changes in Sertoli cells and junctional complexes of the BTB in adult Japanese quail (Coturnix coturnix japonica) exposed to DBP prior to puberty. A total of 25 Japanese quail were used for the study. Exposure to DBP doses of 50, 200 and 400 mg DBP/kg/d caused dose‐related ultrastructural changes in junctional complexes including dilation and separation, while disruption of cytoplasmic membranes and mitochondria was observed in Sertoli cells. There was a significant difference in the sum of vacuoles, vacuole diameter, nuclear width, nuclear length, nuclear area, sum of damaged spherical mitochondria, width of elongated mitochondria and the sum of damaged elongated mitochondria among the five treatment groups (p ˂ 0.05). Prepubertal exposure to DBP at doses of 50, 200 and 400 mg DBP/kg/d for 30 days led to adverse effects in the adult male Japanese quail reproductive system by inducing structural changes in the Sertoli cells and junctional complexes. Such changes might disrupt the BTB and potentially interfere with spermatogenesis. Results indicated that the Sertoli cell is sensitive to DBP exposure and might be an important cellular target for DBP‐induced testicular toxicity. [ABSTRACT FROM AUTHOR]

One of the main environmental toxins that pose a risk to human health is cadmium (Cd) which especially affected human fertility. This investigation aimed to study whether the Stem Enhancer® was able to treat cadmium chloride-evoked testicular toxicity or not. About 36 male rats were divided into 6 groups equally: the control group, tween80 group, and StemEnhance® group received 198mg/kg b. w. /days orally, cadmium chloride group (Cdcl2) received 15 mg/kg b.w. / day orally for 45 consecutive days, Cdcl2+distilled water group received Cdcl2 15mg/kg/day orally for 45 days, and then it received distilled water orally for another 45 days and Cdcl2+ StemEnhance®group received Cdcl2 15mg/kg/day orally for 45 days, and then it received StemEnhance® 198 mg/kg body weight /days orally for another 45 days. The results demonstrated that CdCl2 reduced sperm motility, count, and relative weight of testes and increased the percentage of dead sperm and sperm abnormalities and caused histopathological alterations. CdCl2 and decreased level of testosterone, FSH and testicular total antioxidant level in serum. However, the sperm profile of rats in the StemEnhance® treated group was improved, as the testosterone, FSH and total antioxidant capacity increased. So by inhibiting oxidative stress and acting as a bone marrow stem cell mobilizer, StemEnhance®, according to our findings, may be able to treat testicular damage caused by cadmium chloride. [ABSTRACT FROM AUTHOR]

Background: Application of doxorubicin (DOX) in cancer patients is limited due to its dose-dependent toxicity to nontarget tissues such as testis and subsequent infertility. Due to limitation of our knowledge about the mechanisms of DOX toxicity in the reproductive system, reduction of DOX-induced testicular toxicity remains an actual and primary clinical challenge. Considering the potentials of troxerutin (TXR) in generating a protective phenotype in many tissues, we aimed to examine the effect of TXR on DOX-induced testicular toxicity by evaluating the histological changes and the expression of mitochondrial biogenesis genes and microRNA-140 (miR-140). Materials and Methods: Twenty-four adult male Wistar rats (250-300 g) were divided in groups with/ without DOX and/or TXR. DOX was injected intraperitoneally at 6 consecutive doses over 12 days (cumulative dose: 12 mg/kg). TXR (150 mg/kg/day; orally) was administered for 4 weeks before DOX challenge. One week after the last injection of DOX, testicular histopathological changes, spermatogenesis activity, and expression of mitochondrial biogenesis genes and miR-140 were determined. Results: DOX challenge significantly increased testicular histopathological changes, decreased testicular expression profiles of sirtuin 1 (SIRT-1) and nuclear respiratory factor-2 (NRF-2), and increased expression of miR-140 (P < 0.05 to P < 0.01). Pretreatment of DOX-received rats with TXR significantly reversed testicular histopathological changes, spermatogenesis activity index, and the expression levels of SIRT-1, peroxisome proliferator-activated receptor-γ coactivator 1-alpha (PGC-1α), NRF-2, and miR-140 (P < 0.05 to P < 0.01). Conclusion: Reduction of DOX-induced testicular toxicity following TXR pretreatment was associated with upregulation of SIRT-1/PGC-1α/NRF-2 profiles and better regulation of miR-140 expression. It seems that improving microRNA-mitochondrial biogenesis network can play a role in the beneficial effect of TXR on DOX-induced testicular toxicity. [ABSTRACT FROM AUTHOR]

Acrylamide (ACR) is used in many fields such as cosmetics, paper, and textile industries. It also occurs at very high temperatures in some foods. Gonadotoxic effects of ACR have been found in experimental animals. Many studies use flavonoids to prevent the reproductive side effects of ACR. Naringin (NA) is a flavonoid and it has been determined by studies that it has no toxic effect on tissues. In our study, we aimed to determine the protective effect of NA against the damage of ACR on testicular tissue and the reproductive system in rats. In our study, 50 Spraque Dawley male rats weighing 220‐250 grams were used. Control: Only intragastric saline was administered for 10 days. ACR: Animals received ACR (40 mg/kg, intraperitoneally) for 10 days. NA50+ACR: Animals were given NA for 10 days and each NA was one hour after the administration of ACR. NA100+ACR: Animals received NA for 10 days and one hour after each NA was given ACR. NA100: Animals were given NA for 10 days. At the end of the applications, the rats were euthanized by cervical dislocation under anesthesia. Serum FSH, LH, and Dihydrotestosterone levels were compared between the groups. In addition, oxidative stress, inflammation, expression of some reproductive enzymes, and apoptosis markers were determined in testicular tissues. When these parameters were compared between groups, ACR induced testicular dysfunction and tissue damage in rats. We determined that only the NA application did not cause tissue damage. and the administration of NA along with ACR significantly reduced ACR‐induced testis toxicity. [ABSTRACT FROM AUTHOR]

Male reproductive toxicity is a well-established side effect of the chemotherapeutic drug adriamycin (ADR). Sildenafil (SIL) is a phosphodiesterase inhibitor known to enhance the chemosensitivity of cancer cells to ADR. However, there is a scarcity of information on the effect of SIL on ADR-induced testicular toxicity. In this study, SIL (5, 10, or 20 mg/kg/day) was administered to male rats for 7 days, followed by a single intraperitoneal injection of ADR (20 mg/kg) on day 7. Control rats received either ADR, SIL, or normal saline for 7 days. Epididymal sperm were collected from the testes to assess the effects on sperm quality, quantity, and serum testosterone concentration was also determined. ADR treatment caused a decrease in sperm motility and elevated the percentage of sperms with tail defects which worsened in combination with SIL (20 mg/kg). Furthermore, ADR alone or in combination with SIL dose-dependently increased total sperm abnormalities. SIL (20 mg/kg) plus ADR also decreased sperm count and lowered testosterone level compared to ADR-only rats. In conclusion, exposure of rats to SIL before ADR treatment has the potential to worsen ADR-induced testicular toxicity. [ABSTRACT FROM AUTHOR]

Objective: Testicular tissues and sperms are typically vulnerable to oxidative stress and inflammation. Despite functioning as a signaling molecule in different physiological and pathological processes, hydrogen sulfide (H2S) role in the reproductive system is not fully recognized. This study aimed to assess whether H2S could counteract the testicular damage that acrylamide (AC) causes in male rats. Methods: Forty male rats were equally divided randomly into four groups: normal control, AC, H2S, and AC + H2S who received normal saline, 40 mg/Kg of AC, 200 µg/Kg of sodium hydrosulfide NaHS (H2S donor), and 40 mg/Kg of AC + 200 µg/Kg of NaHS by intraperitoneal injection for 14 consecutive days, respectively. Body and testes weights, sperm count and motility, lactate dehydrogenase isoenzyme-x (LDH-X), serum testosterone level, oxidative parameters, the expression level of inducible nitric oxide synthase (iNOS), inflammatory cytokines, and histopathological alterations were evaluated. Results: The reduction in relative testicular weights, sperm count, and motility served as evidence of the harmful effects of AC. However, these values were reversed when H2S and AC were combined. Additionally, AC significantly decreased serum testosterone level, testicular LDH-X activity, superoxide dismutase, catalase, and reduced glutathione. While malondialdehyde, expression levels of iNOS protein and inflammatory cytokines (TNF-α, IL-1β, and IL-6) levels were elevated. Interestingly, the co-administration of H2S with AC reversed these values, demonstrating an opposing effect in the previous parameters. Conclusion: H2S exhibited a protective effect in the rat model of testicular toxicity induced by AC, which may be associated with the suppression of iNOS expression, proinflammatory cytokines, and the inhibition of oxidative stress injury. [ABSTRACT FROM AUTHOR]

Fruit of Carissa opaca Stapf ex Haines (C. opaca) is a feed additive and is commonly used against cardiac dysfunction, fever, asthma, diarrhea, gastrointestinal ailments, and skin diseases. In this study, we aimed to evaluate the metabolic profile and antioxidant potential of C. opaca fruit against carbon tetrachloride (CCl4)-induced cardiotoxicity and testicular toxicity in rats. Gas Chromatoghraphy-Mass Spectrometry (GC-MS) analysis of C. opaca fruit for the identification of potential metabolic profile, followed by methanolic extract of C. opaca and its derived fractions including n-hexane, ethyl acetate, chloroform, butanol, and aqueous were used to assess the antioxidant potential of fruits. Ten groups of rats received different treatments and got evaluated for cardiac and testicular antioxidant enzymes, histological architecture, and serum hormonal levels. GC-MS analysis of methanolic extract of C. opaca fruit showed the presence of some bioactive metabolites like cyclodecane, diethyl 2,6-pyridine dicarboxylate, tetrahydro-geraniol, S-[2-[N, N-Dimethylamino]ethyl]morpoline, 2,3-Methylenedioxyphenol, alpha-d-Glucopyranoside, 5,10-Diethoxy-2,3,7,8-tetrahydro-1H, 6H-dipyrrolo [1,2-a; 1′,2′-d] pyrazine and 1,3-Benzothiazol-2(3H)-one,3-(3,3-dimethyl-1-oxobutyl) that corresponds the medicinal properties of C. opaca fruit. Prepared fractions of C. opaca fruits mitigated the toxicity induced by CCl4 in the heart and testicular tissues of rats. Oxidative stress was caused by the inhibition of activities of glutathione and other antioxidant enzymes of the body, while on the other hand elevating the levels of nitrite and hydrogen peroxide. Treatment with C. opaca fruit extract normalized the levels of enzymes, reproductive hormones, and free radicals thus restoring the histopathological and enzymatic biomarkers towards the normal group. The study supports the indigenous use of fruits as an alternative medicine against cardiac dysfunction by providing scientific evidence of protection against CCl4-induced injuries, and it also concludes the antioxidant defensive role in testicular tissues.

The purpose of this study was to investigate the protective effect of Beta vulgaris leaf extract (BVLE) on Fe2+-induced oxidative testicular damage via experimental and computational models. Oxidative testicular damage was induced via incubation of testicular tissue supernatant with 0.1 mM FeSO4 for 30 min at 37 °C. Treatment was achieved by incubating the testicular tissues with BVLE under the same conditions. The catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels, acetylcholinesterase (AChE), sodium-potassium adenosine triphosphatase (Na+/K + ATPase), ecto-nucleoside triphosphate diphosphohydrolase (ENTPDase), glucose-6-phosphatase (G6Pase), and fructose-1,6-bisphosphatase (F-1,6-BPase) were all measured in the tissues. We identified the bioactive compounds present using high-performance liquid chromatography (HPLC). Molecular docking and dynamic simulations were done on all identified compounds using a computational approach. The induction of testicular damage (p

Background: Polystyrene microplastics (PS-MPs) have become major environmental pollutants that adversely effects multiple organs specifically testicles. Pinostrobin (PN) is an important flavonoid which, shows several pharmacological potentials. Purpose: The current study was designed to elucidate the mitigative effects of PN against PS-MPs induced testicular toxicities in rats. Methods: 48 male albino rats were randomly distributed into 4 groups, control, PS-MPs group (0.01 mg/kg), PS-MPs + PN group (0.01 mg/kg of PS-MPs; 40 mg/kg of PN) and PN group (40 mg/kg). Results: PS-MPs intoxication substantially lessened the activities of glutathione peroxidase (GPx), glutathione reductase (GSR), superoxide dismutase (SOD) along with catalase (CAT) while, raised the level of malondialdehyde (MDA) as well as reactive oxygen species (ROS). Additionally, PS-MPs reduced luteinizing hormone (LH), plasma testosterone, follicle-stimulating hormone (FSH) concentration, sperm motility, sperm count, expression of steroidogenic enzymes and Bcl-2 (anti-apoptotic protein) along with the count of spermatogenic cells. While, dead sperm count, sperm abnormalities (tail, neck and head), Bax and caspase-3 (apoptotic proteins) expression along with histopathological anomalies were elevated. Moreover, PS-MPs exposure increased the level of inflammatory markers. However, PN treatment considerably decreased oxidative stress (OS) by reducing ROS as well as increased sperm motility and alleviated all the damages induced by the PS-MPs. Conclusion: Therefore, it is concluded that PN may prove a potential therapeutic candidate to restore all the PS-MPs-induced testicular toxicities.

Chia seeds offer therapeutic properties that aid in the prevention of a variety of ailments, including cardiovascular disease, diabetes, obesity, and other risk factors. Arsenite, a common environmental chemical, has been identified as a reproductive toxin owing to its negative effects on male reproductive health. It has been shown to inhibit spermatogenesis and generate androgenic effects in men. The primary goal of this research was to look into the effect of Salvia hispanica on testicular toxicity caused by sodium arsenite in male rats. A set of 36 male albino rats was allocated to a negative control cohort. The individuals in this group were given a basic meal and orally given distilled water for a duration of 28 days. The other five groups were given a regular meal and received intra-peritoneal injections of sodium arsenite (NaAsO2) at a concentration of 4 mg/kg body weight that was diluted in a 0.9% NaCl solution. The injections were administered consecutively, with two doses given within a two-day period. Subsequently, the rats were categorized into several groups using the following classification: Group 2 consisted of a positive control cohort, in which the rats were given a typical baseline diet. Groups 3, 4, 5, and 6 were given a basic diet that included varying proportions of ground chia seeds, namely 5%, 10%, 15%, and 20% per 100 g of the diet. After the trial was completed, the rats were euthanized, and further biological examination was conducted. The measurements of the reproductive organs were documented and reported. The research assessed the following characteristics: sperm count, motility, progressive motility, and normal morphology. The research included examining serum sex hormones, namely luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. An evaluation of the activity of antioxidant enzymes was performed in the tissue of the testicles. There were statistically significant improvements in the sperm parameters, serum sex hormone levels, and the activity of antioxidant enzymes, such as GPX, SOD, and CAT, in the therapy groups. The levels of malondialdehyde (MDA) exhibited a noteworthy decrease (p ≤ 0.05) when compared to the positive control group. Salvia hispanica seeds have demonstrated a significant level of effectiveness in reducing sodium arsenite-induced testicular toxicity, which leads to the conclusion. The flavonoid content and antioxidant properties of Salvia hispanica seeds may be to blame for the observed behavior. These indicated characteristics may have therapeutic significance in treating testicular harm induced by arsenite exposure.

Doaa Abdallah El-Naggar,1 Laila Mohammed Ahmad El-Zalabany,1 Doaa Abdelhalim Shahin,2 Afaf Mahmoud Attia,1 Shaaban Abdelfattah El-Mosallamy1 1Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Dakahliya, Egypt; 2Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Dakahliya, EgyptCorrespondence: Doaa Abdallah El-Naggar, Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Tel +20 1063433525, Dakahliya, Egypt, Email dr_doaaelnaggar@yahoo.comBackground: Chloroxylenol (para-chloro-meta-xylenol, PCMX) is claimed to be highly harmful both to humans and the environment. Toxic effects of PCMX on testicular functions are scarcely discussed in the literature.Aim of Study: To study testicular toxic effects of PCMX on male Sprague-Dawley rats.Materials and Methods: Forty animals were randomly distributed into three groups: negative control (G I), vehicle group (G II) and PCMX group (G III). PCMX group was subdivided into three subgroups: GIIIa: received PCMX 100 mg/kg, GIIIb: received PCMX 200 mg/kg and G IIIc: received PCMX 500 mg/kg. Hormonal assay included assessment of serum testosterone and estradiol levels. Histopathological examination of testicular tissue, analysis of cellular viability, necrosis and apoptosis in testicular tissue by flow cytometry, analysis of cellular DNA content and phases of cell cycle analysis by flow cytometry were also performed.Results: Rats in the groups exposed to PCMX (G IIIa, G IIIb and G IIIc) had significantly lower estradiol and testosterone levels in comparison to control groups (G I and GII). Histopathological examination of testicular tissue of PCMX-exposed rats showed irregular crossly sectioned seminiferous tubules with their lumina containing scanty spermatids and spermatozoa. G IIIc animals showed eosinophilic proteinaceous material and vacuolated and necrotic interstitial cells of Leydig. Rats in PCMX-exposed groups (G IIIa, G IIIb and G IIIc) showed significantly lower testicular tissue viability in comparison to control groups (G I and G II). Rats in PCMX-exposed groups (G IIIa, G IIIb and G IIIc) showed significantly lower percentage of cells in the G0/G1 phase in comparison to control groups (G I and G II).Conclusion: Rats exposed to PCMX had significant reduction in testosterone and estradiol levels with marked histopathological alterations affecting testicular tissues. These effects are dose-dependent.Keywords: chloroxylenol toxicity, testicular toxicity, cell cycle, semen analysis

Aflatoxin B1 (AFB1) is an extremely hazardous and unavoidable pollutant for cereals and feedstuff. AFB1 can cause testicular lesion, and how to alleviate its testicular toxicity has received much attention in recent years. Lycopene (LYC), a foodborne nutrient derived from red fruits and vegetables, has protective effects against sperm abnormality and testicular lesions. To confirm the beneficial effects and mechanisms of LYC on AFB1-induced testicular lesion, 48 male mice were exposed to 0.75 mg/kg AFB1 or/and 5 mg/kg LYC for consecutive 30 days. Results demonstrated the LYC significantly restored the lesions of testicular microstructure and ultrastructure, and sperm abnormalities in AFB1-exposed mice. Furthermore, LYC effectively attenuated AFB1-induced oxidative stress and mitochondrial damage, including ameliorative mitochondrial structural, and elevated mitochondrial biogenesis for maintaining mitochondrial function. Meanwhile, LYC resisted AFB1-induced mitochondrial-dependent apoptosis. In addition, LYC promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and upregulated the Nrf2 signaling pathway. Collectively, our findings demonstrate LYC ameliorates AFB1-induced testicular lesion by attenuating oxidative stress and mitochondrial damage, which is related to the activation of Nrf2.

Cisplatin (CISP) ranks among the most used chemo-therapeutic agents with exceptional efficacy against testicular cancer among other diverse types of cancers. However, it has been associated with nephrotoxicity among other side effects. Pomegranate (PE) is an effective anti-inflammatory and antioxidant compound, protecting against several chemotherapy-linked toxicities. The use of PE are limited due to its low bioavailability and poor solubility. We investigated the potential of a novel nanoparticle (NP) encapsulating PE formulation to surmount its poor solubility, improve its bioavailability, and augment its protective efficacy against CISP-induced testicular toxicity in an Ehrlich solid carcinoma (ESC) mice model. All animals were randomly grouped into four treatment groups: 1) control, 2) tumor, 3) CISP, and 4) CISP + PE-NPs. The results obtained demonstrated that PE-NPs efficiently prevented testicular toxicity induced by CISP in ESC mice and enhanced its functions. PE-NPs effectively improved CISP-induced oxidative stress in testicular tissues by elevating the levels of antioxidants (GSH, SOD and CAT). Importantly, PE-NPs, also, substantially decreased testicular inflammation induced by CISP, via reducing the levels of IL-1β, TNF-α, and NF-kB. PE-NPs did not impede the CISP’s antitumor activity as shown by histological examination data and tumor weight. It is, therefore, conceivable that PE-NPs may serve as an adjuvant therapy to CISP in the treatment of cancer, to ameliorate the associated testicular toxicity and other unwanted effects without compromising the antitumor efficacy of CISP.

In non-clinical animal studies for drug discovery, histopathological evaluation is the most powerful tool to assess testicular toxicity. However, histological analysis is extremely invasive; many experimental animals are needed to evaluate changes in the pathology and anatomy of the testes over time. As an alternative, small animal magnetic resonance imaging (MRI) offers a non-invasive methodology to examine testicular toxicity without radiation. The present study demonstrated the suitability of a new, ready-to-use compact MRI platform using a high-field permanent magnet to assist with the evaluation of testicular toxicity. To validate the utility of the MRI platform, male mice were treated with busulfan (40 mg/kg, intraperitoneal injection). Twenty-eight days after treatment, both testes in busulfan-treated and control mice (n = 6/group) were non-invasively scanned in situ by MRI at 1 tesla. On a T1-weighted 3D gradient-echo MRI sequences (voxel size: 0.23 × 0.23 × 0.50 mm), the total testicular volume in busulfan-treated mice was significantly smaller than in controls. On T1-weighted images, the signal intensity of the testes was significantly higher in busulfan-treated mice than in controls. The mice were sacrificed, and the testes were isolated for histopathological analysis. The weight of the testes in busulfan-treated mice significantly decreased, similar to the results of the non-invasive analysis. Additionally, periodic acid-Schiff stain-positive effusions were observed in the interstitium of the busulfan-treated mouse testes, potentially explaining T1 shortening due to a high concentration of glycoproteinaceous content. The present data demonstrated a rapid evaluation of testicular toxicity in vivo by compact MRI. [ABSTRACT FROM AUTHOR]

BACKGROUND: Phthalates (PEs), such as butyl benzyl phthalate, dibutyl phthalate and di(2-ethylhexyl) phthalate, are one of the most widely used plasticizers, and humans are increasingly exposed to them. Phytochemical quercetin (Que) is a typical flavonoid with several biological effects, such as antioxidative and anti-inflammatory. The present study was designed to explore the effect of Que on testicular toxicity caused by the mixture of three commonly used PEs (MPEs), and the underlying mechanism. Forty male Sprague-Dawley rats were randomly and equally divided into five groups (n = 8). Rats in control the group were orally treated with the excipient. Rats in the MPEs group were orally administered with 900 mg kg-1 day-1 MPEs, whereas rats in the MPEs+L-Que, MPEs+M-Que and MPEs+H-Que groups were simultaneously treated with 900 mg kg-1 day-1 MPEs and, respectively, 10, 30 and 90 mg kg-1 day-1 Que for 30 days. RESULTS: Compared with the control group, the testes weight, epididymides weight, serum testosterone, luteinizing hormone, follicle-stimulating hormone and estradiol levels, and anogenital distance in the MPEs group were significantly decreased (P < 0.05). The testicular tissues were injured with atrophy of seminiferous tubules, hyperplasia of Leydig cells and arrest of spermatogenesis in the MPEs group. Testicular steroidogenic proteins (StAR, P450scc, CYP17A1 and 17β-HSD, P450arom) were up-regulated, whereas P-element-induced wimpy testis proteins (PIWIL1 and PIWIL2) were down-regulated in the MPEs group (P < 0.05). However, the alterations of these parameters were inhibited in the MPEs+M-Que and MPEs+H-Que groups. CONCLUSION: MPEs disturbed steroid hormone metabolism and caused testicular injuries. Que could inhibit testicular toxicity of MPEs, which might relate to the improved regulation of steroid hormone metabolism. [ABSTRACT FROM AUTHOR]

Diquat is a fast, potent, and widely used bipyridine herbicide in agriculture and it induces oxidative stress in several animal models. However, its genotoxic effects on the male reproductive system remain unclear. Melatonin is an effective free-radical scavenger, which has antioxidant and anti-apoptotic properties and can protect the testes against oxidative damage. This study aimed to investigate the therapeutic effects of melatonin on diquat-induced testicular injury in mice. The results showed melatonin treatment alleviated diquat-induced testicular injury, including inhibited spermatogenesis, increased sperm malformations, declined testosterone level and decreased fertility. Specifically, melatonin therapy countered diquat-induced oxidative stress by increasing production of the antioxidant enzymes GPX1 and SOD1. Melatonin treatment also attenuated diquat-induced spermatogonia apoptosis in vivo and in vitro by modulating the expression of apoptosis-related proteins, including P53, Cleaved-Caspase3, and Bax/Bcl2. Moreover, melatonin restored the blood-testicular barrier by promoting the expression of Sertoli cell junction proteins and maintaining the ordered distribution of ZO-1. These findings indicate that melatonin protects the testes against diquat-induced damage by reducing oxidative stress, inhibiting apoptosis, and maintaining the integrity of the blood–testis barrier in mice. This study provides a theoretical basis for further research to protect male reproductive health from agricultural pesticides. [ABSTRACT FROM AUTHOR]

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This present study was designed to investigate ameliorating potential of thymol (THY) on hexachlorobenzene (HBC)-induced epididymal and testicular toxicities in adult male rats. Forty adult male rats were orally treated by gavage daily for 28 consecutive days and divided into four groups; control group administered with corn oil, HBC-treated group (16 mg/kg b. wt), thymol-treated group (30 mg/kg b. wt), and HBC + THY-treated group. The results revealed that HBC exposure caused a significant decrease in the body weight change, organ weights, sperm functional parameters, serum testosterone level with widespread histological abnormalities. Furthermore, HBC-treated rats showed increased in the serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), epididymal and testicular myeloperoxidase activity, tumor necrosis-α, interleukin-1β level and caspase-3 activity, induced oxidative damage as evidenced by elevated malondialdehyde (MDA), reactive oxygen species (RONS) levels and significant reduction in antioxidant enzyme activities and reduced glutathione (GSH). However, co-treatment of THY with HBC alleviated the HBC-induced epididymal and testicular toxicities. Our findings revealed that HBC acts as a reproductive toxicant in rats and thymol could be a potential remedial agent for HBC-induced reproductive toxicity. [ABSTRACT FROM AUTHOR]

Infertility is a major global health issue and male factors account for half of all infertility cases. One of the causes of male infertility is the loss of spermatogonial stem cells, which may occur because of chemotherapy, radiotherapy or genetic defects. In numerous animal species, the evidence suggests the pineal gland and melatonin secretion in their reproductive activities are involved. Recently, considerable attention has pointed to the usage of melatonin in the treatment of diseases. Melatonin is associated with the regulation of circadian and seasonal rhythmic functions, immune system functions, retinal physiology, spermatogenesis and inhibition of tumour growth in different species. Several studies demonstrated that melatonin acts as an anti‐apoptotic, anti‐inflammatory, anticancer and antioxidant agent. Melatonin can also protect testicles and spermatogonia against oxidative damage, chemotherapy drugs, environmental radiation, toxic substances, hyperthermia, ischemia/reperfusion, diabetes‐induced testicular damage, metal‐induced testicular toxicity, improve sperm quality and it affects the testosterone secretion pathway by affecting Leydig cells. Therefore, the objective of this study is to investigate the biological effects of melatonin as a natural antioxidant on testicles and their disorders. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the potential mitigating effect of fisetin on monosodium glutamate (MSG)-induced testicular toxicity and investigate the possible involvement of silent mating type information regulation 2 homolog 1 (SIRT1) in this effect. Forty male rats were divided into normal control, fisetin-treated, MSG-treated, and fisetin + MSG-treated groups. Testosterone, GnRH, FSH, and LH were measured in plasma, as well as SIRT1 and phosphorylated AMP-activated protein kinase (pAMPK) levels in testicular tissues using ELISA. Hydrogen peroxide (H2O2), nitric oxide (NO), and reduced glutathione (GSH) were measured colorimetrically, while Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) expression was relatively quantified using RT–PCR in testicular tissues. After 30 days, fisetin could ameliorate MSG-induced testicular toxicity by acting centrally on the hypothalamic-pituitary-gonadal axis, increasing plasma levels of GnRH, FSH, LH, and testosterone. Peripheral actions of fisetin on the testis were indicated as it increased testicular SIRT1 and pAMPK. Furthermore, it antagonized glutamate-induced oxidative stress by significantly lowering H2O2, NO, and relative NOX4 expression while significantly increasing reduced GSH levels. It also improved the architecture of the seminiferous tubules, reduced sperm abnormality, and increased sperm count. Fisetin ameliorates MSG-induced testicular toxicity via central and peripheral mechanisms making it a promising therapeutic target for male infertility. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is a commonly used chemotherapeutic drug that has adverse toxic effects on germ cells. Naringin (NG) is a natural flavanone glycoside, with different phytotherapeutic applications, and its possible protective effects against MTX-induced testicular tissue damage were investigated in this study. Low and high doses of NG (40 and 80 mg/kg/day) were given for 10 days by intraperitoneal (i.p.) injection and MTX (20 mg/kg i.p.) was given at the 4th day of the experiment, with or without NG in rats. The obtained results showed that exposure to MTX increased malondialdehyde (MDA) levels and nitric oxide (NO) production compared with the control. In the meantime, MTX depleted catalse (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), and reduced glutathione (GSH) in the testicular tissue. Further, serum testosterone levels were significantly decreased in the MTX group. NG significantly counteracted the aforementioned effects of MTX; however, NG80 was more effective in restoring SOD, GR, MDA and NO. Interestingly, NG80 achieved a better improvement in the ultrastructural pattern of the testicular cells in MTX-exposed rats. These results indicated, for the first time, that NG could be a potential candidate therapy against MTX-reprotoxic impacts. [ABSTRACT FROM AUTHOR]

Cadmium is a heavy toxic metal with unknown biological functions in the human body. Over time, cadmium accretion in the different visceral organs (liver, lungs, kidney, and testis) is said to impair the function of these organs, which is associated with a relatively long biological half-life and a very low rate of excretion. Recently studies have revealed that the testes are highly sensitive to cadmium. In this review, we discussed the adverse effect of cadmium on the development and biological functions of the testis. The Sertoli cells (SCs), seminiferous tubules, and Blood Testis Barrier are severely structurally damaged by cadmium, which results in sperm loss. The development and function of Leydig cells are hindered by cadmium, which also induces Leydig cell tumors. The testis's vascular system is severely disturbed by cadmium. Cadmium also perturbs the function of somatic cells and germ cells through epigenetic regulation, giving rise to infertile or sub-fertile males. In addition, we also summarized the other findings related to cadmium-induced oxidative toxicity, apoptotic toxicity, and autophagic toxicity, along with their possible mechanisms in the testicular tissue of different animal species. Consequently, cadmium represents a high-risk factor for male fertility. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is one of the chemicals that cause dysfunction and infertility in testicles. Therefore, it is crucial to develop effective treatments against this damage. In this study, the effects of Hesperidin (HESP), a flavonoid in testicular toxicity induced by BPA in rats, on oxidative stress, inflammation, apoptosis, histological damage, spermatogenesis, steroidogenic enzymes and reproductive hormones were investigated. Our study used 52 Sprague Dawley male rats weighing 250–300 g, and four experimental groups were formed. From the experimental groups, 1 ml of olive oil was administered to the control group, HESP at a dose of 50 mg/kg to the HESP group, BPA at a dose of 100 mg/kg to the BPA group, HESP at a dose of 50 mg/kg to the BPA + HESP group and 100 mg/kg BPA was administered intragastrically (ig) for 14 days. We determined that BPA administration causes apoptosis, histological damage, inflammation, oxidative stress and toxic effects on spermatogenesis and steroidogenic enzymes in testicles. We observed that the administration of HESP with BPA attenuated oxidative stress, inflammation and apoptosis resulting in therapeutic effects on both steroidogenic enzymes and spermatogenesis and reproductive hormones (FSH, LH and testosterone). Our findings from this study clearly showed that while HESP treatment alleviates oxidative damage, inflammation and apoptosis in testicles of rats treated with BPA, it has regulatory effects on steroidogenic enzymes, spermatogenesis and serum reproductive hormones. [ABSTRACT FROM AUTHOR]