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Di-n-butyl phthalate (DBP) is a phthalate-based material used as a plasticizer to soften polyvinyl chloride, and classified as an endocrine disruptor with antiandrogen effects. Exposure to DBP induces oxidative stress in rat testes, resulting in testicular toxicity. Black ginseng (BG) exhibits a higher antioxidant activity than white or red ginseng following repeated heat treatment and processing. This study aimed to investigate whether the antioxidant activity of BG might protect against DBP-induced testicular toxicity in juvenile Sprague-Dawley rats. A significant decrease in testicular weight was observed in most groups treated with DBP alone or in combination with BG. However, a significant testicular weight increase was detected after exposure to BG (10 ml/kg) + DBP (500 mg/kg). The epididymal weight was significantly reduced with associated histological changes including irregular arrangement, atrophy of seminiferous tubules and Sertoli cells, and Leydig cell damage following exposure to DBP alone as well as BG (2.5 ml/kg) + DBP (500 mg/kg). However, no marked changes were observed in the shape of seminiferous tubules in control and BG + DBP groups. A significant decrease in serum testosterone levels was found after exposure to DBP, but no marked alterations in the BG + DBP groups. Protein expression levels of nuclear factor erythroid-derived 2-related factor (Nrf2), NAD(P)H dehydrogenase 1 (NQO1), and, heme oxygenase-1; (HO-1) were significantly higher following DBP treatment, but lowered in the BG + DBP groups. Evidence indicates that BG exerts a protective effect against DBP-induced testicular toxicity in rats. [ABSTRACT FROM AUTHOR]

Reproductive toxicology is a discipline that uses toxicological methods to study the mechanisms by which foreign substances interfere with the generation of eggs or sperm and their detrimental effects on offspring. Research includes evaluating the damaging effects of test substances on reproductive function of parents and the toxicity evaluation of offspring embryos. People are exposed to a wide range of drugs, chemicals and environmental pollutants on a daily basis, and determining whether these substances have reproductive toxicity is crucial for the health of future generations. Reproductive toxicology research is therefore critical. Given the specificity and importance of reproductive toxicity evaluation, corresponding institutions both domestically and internationally have issued guidelines, national standards, or industry standards, all of which involve animal experiments. In the study of reproductive system diseases, numerous animal models have been developed to investigate key reproductive organs, such as testicles and ovaries. Each model involves the selection of animals, the establishment of methods, and the quantification of evaluation indicators, and all have advantages and limitations. The choice of model should be based on experimental needs and the characteristics of the model. This paper summarizes commonly used animal models for reproductive and development toxicity evaluation in reproductive toxicology research, including rat models for fertility and early embryonic development toxicity, rat models for embryo-fetal development toxicity, rabbit models for embryo-fetal development toxicity evaluation, minipig models for embryo-fetal development toxicity, rat models for perinatal toxicity, zebrafish models for embryonic development toxicity, and models for evaluating ovarian toxicity induced by chemical drugs, radiotherapy, autoimmunity, and ovariectomy, as well as models for evaluating testicular toxicity caused by chemical drugs and environmental factors. The methods for establishing these models, their application scope, and characteristics are reviewed in order to provide references for relevant research applications. [ABSTRACT FROM AUTHOR]

Cisplatin (a platinum-based drug) has chemotherapeutical potency in treating different kinds of cancer but elicits side effects of testicular dysfunction while hesperetin has antioxidant attributes against inflammation, free radicals, and apoptosis. This study investigated the likely protective property of hesperetin against cisplatin-induced testicular and epididymal toxicity. Forty mice randomly assigned into four groups of 10 animals each were administered with the appropriate regimen. Group 1 (control) received normal saline alone while group 2 received 2.5 mg/kg body weight of cisplatin only. Group 3 received 40 mg/kg body weight of hesperetin and 2.5 mg/kg body weight of cisplatin, while group 4 received only 40 mg/kg body weight of hesperetin. Hesperetin administration (orally) was for 30 consecutive days while cisplatin (intraperitoneally) was on days 5, 7, 10, 13, 17, 20, 24, and 28. Findings revealed that cisplatin decreased the activities/level of glutathione peroxidase, superoxide dismutase, reduced glutathione, nitric oxide, total thiol, testosterone, luteinizing hormone, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, sperm viability, sperm motility, and total sperm count while the abnormal sperm cells and levels of lipid peroxidation, H2O2, and inteleukin-1β were increased (P < 0.05). Furthermore, histopathological results of examined testes showed a reduction in the tube-shaped size of testes, diminished development of spermatozoa, and architectural impairment with cisplatin exposure. Contrarily, hesperetin reversed cisplatin-induced testicular and epididymal oxidative damage, suppressed steroidogenesis and spermatogenesis, and repaired the architecture of the testes. The study showed that hesperetin demonstrated multi-mechanistic protective activity against testicular dysfunction, oxidative stress, and histological damage owing to its antioxidant and steroidogenic actions. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of copper (CuSO4) and zinc (ZnSO4) overload on male reproductive toxicity and the potential of a polysaccharide extracted from green alga Chaetomorpha linum (PS) in mitigating their toxicities. Adult male mice strain of 25 ± 2 g of weight was subdivided into eight groups. Group 1 served as control; group 2 received PS (200 mg/kg), and groups 3 and 4 received intraperitoneally zinc (60 mg/kg b.w) and copper (33 mg/kg b.w), respectively. Group 5 received both zinc (60 mg/kg b.w) and copper (33 mg/kg b.w), group 6 received zinc (60 mg/kg b.w) associated with PS (200 mg/kg), group 7 received copper (33 mg/kg b.w) associated with PS (200 mg/kg), and group 8 received zinc (60 mg/kg b.w) and copper (33 mg/kg b.w) associated with PS (200 mg/kg). Results suggested that ZnSO4 and CuSO4 significantly decreased the functional sperm parameters. Furthermore, extended exposure to these elements increased oxidative stress biomarkers, including malondialdehyde (MDA) as a measure of lipid peroxidation and advanced oxidation protein products (AOPP) indicating protein oxidative damage. This process also reduces the activity of antioxidant enzymes such as glutathione (GSH) and glutathione peroxidase (GPx), which neutralize and catalyze free radicals. Histopathological changes in mice testis were also studied. However, the co-treatments with PS significantly reduced these effects and promoted the reproductive parameters in male mice. In conclusion, PS exhibited protective effects against zinc and copper-induced reproductive toxicity, making it a potential adjuvant treatment for testicular toxicity. [ABSTRACT FROM AUTHOR]

Background The tobacco epidemic signifies a major public health threat. Nicotine (NIC), a major active constituent in tobacco, impedes male fertility and semen quality. This work is implemented to explore the potential of selenium nanoparticles (SeNPs) and the newly fabricated SeNPs @vitamin C (SeNPs@VITC) nanocomposite in mitigating testicular toxicity induced by NIC. Materials and methods The six groups of 48 adult Wistar rats were designed as follows: the control group injected intraperitoneally with normal saline, the SeNPs group treated orally with 2 mg/kg of SeNPs, the SeNPs@VITC nanocomposite group treated orally with 2 mg/kg of SeNPs@VITC nanocomposite, the NIC group injected intraperitoneally with 1.25 mL/kg of NIC, the NIC+ SeNPs group received SeNPs plus NIC, and the NIC+ SeNPs@VITC nanocomposite group received SeNPs@VITC nanocomposite plus NIC. Treatments were administered over a 28-day period. Results NIC treatment significantly caused poor sperm quality, decreased serum testosterone, increased follicle-stimulating hormone (FSH), luteinizing hormone (LH) concentrations, reduced hemoglobin levels, leukocytosis, disrupted testicular oxidant/antioxidant balance, and disorganized testicular structure. The construction of the novel SeNPs@VITC nanocomposite, compared to NIC plus SeNPs alone, demonstrated a more potent ameliorative effect on NIC-induced reproductive toxicity in adult rats. The SeNPs@VITC nanocomposite significantly increased sperm count, reduced the percentage of sperm head abnormalities, lowered both serum FSH and LH concentrations, and improved the hemoglobin response. Conclusions Both SeNPs and SeNPs@VITC nanocomposite alleviated the testicular toxicity induced by NIC, but the SeNPs@VITC nanocomposite exhibited superior efficacy. The SeNPs@VITC nanocomposite could be employed to advance enhanced therapeutic strategies for addressing male infertility. [ABSTRACT FROM AUTHOR]

Mercuric chloride (HgCl2) is a heavy metal that is toxic to the human body. Carvacrol (CAR) is a flavonoid found naturally in plants and has many biological and pharmacological activities including anti-inflammatory, antioxidant, and anticancer activities. This study aimed to investigate the efficacy of CAR in HgCl2-induced testicular tissue damage. HgCl2 was administered intraperitoneally at a dose of 1.23 mg/kg body weight alone or in combination with orally administered CAR (25 mg/kg and 50 mg/kg body weight) for 7 days. Biochemical and histological methods were used to investigate oxidative stress, inflammation, apoptosis, and autophagy pathways in testicular tissue. CAR treatment increased HgCl2-induced decreased antioxidant enzyme (SOD, CAT, and GPx) activities and GSH levels. In addition, CAR reduced MDA levels, a marker of lipid peroxidation. CAR decreased the levels of inflammatory mediators NF-κB, TNF-α, IL-1β, COX-2, iNOS, MAPK14, MAPK15, and JNK. The increases in apoptotic Bax and Caspase-3 with HgCl2 exposure decreased with CAR, while the decreased antiapoptotic Bcl-2 level increased. CAR reduced HgCl2-induced autophagy damage by increasing Beclin-1, LC3A, and LC3B levels. Overall, the data from this study suggested that testicular tissue damage associated with HgCl2 toxicity can be mitigated by CAR administration. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) can be applied to treat several cancers. DOX-induced oxidative stress causes testicular damage. Diosmin (DIO), as a potent antioxidant, reduces many drugs' side effects. We determined DIO therapeutic effects on DOX-related testicular toxicity. Forty rats were assigned to five groups as control, DOX (2.5 mg/kg six i.p. injections at equal intervals over two weeks), DOX + DIO (25, 50, 100 mg/kg, orally, daily, for two weeks) groups. Oxidative and antioxidant markers, fertility parameters levels, sperm parameters, and a histopathological examination were analyzed. DOX group showed a significant decrease in the number of spermatogonia, primary spermatocytes, and sertoli cells, seminiferous tubular diameter, seminiferous luminal diameter, and seminiferous epithelial height. Moreover, testosterone levels, glutathione (GSH) levels, catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities showed a significant decrease. Furthermore, nitric oxide (NO) and malondialdehyde (MDA) contents and also follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels showed a significant increase in the DOX group compared to the control group. DIO improved DOX-related alterations in levels of hormones, spermatogonia, spermatocytes, and sertoli cell number, and seminiferous diameters (tubular, luminal, and epithelial height). Furthermore, GSH level, SOD, GPx, and CAT activities showed a significant increase, and MDA and NO contents showed a significant decrease in the DOX + DIO group than the DOX group. The results indicate that DIO mitigate DOX‐induced testicular toxicity by its anti-oxidant activity. [ABSTRACT FROM AUTHOR]

Recently, it was reported that a testicular organ culture system (TOCS) using polydimethylsiloxane (PDMS) chips with excellent oxygen permeability and biocompatibility, called the PDMS-chip ceiling (PC) method, enables improved spermatogenesis efficiency. We investigated whether this PC method is useful for detecting impaired spermatogenesis caused by busulfan (Bu), a typical testicular toxicant. In this study, testicular tissue fragments from Acro3-EGFP mice, which express the green fluorescent protein (GFP) and reflect the progression of spermatogenesis, were subjected to the PC method. When treated with Bu, cultured tissues shrank in volume, and their GFP-expressing area decreased or disappeared. Histological examination confirmed the regression of spermatogenesis. In addition, immunohistochemical examination revealed that spermatogonia, including spermatogonial stem cells (SSCs), were the primary targets of Bu toxicity. Time-course analysis demonstrated that the recovery of spermatogenesis, dependent on Bu concentration, correlated closely with the severity of damage to these target cells. These results suggest that the PC method is a useful approach for detecting spermatogenesis impairment accurately through faithful recapitulation of spermatogenesis in vivo. [ABSTRACT FROM AUTHOR]

Objective: Cisplatin (CP) is a widely used chemotherapeutic agent, but its severe side effects impact testicular function. We investigated the potential protective effects of bilberry extract against CP-induced testicular toxicity. Methods: Forty adult male albino rats were divided into four groups. Control animals received a single oral dose of 0.9% saline. Bilberry-treated rats received oral bilberry extract (200 mg/kg body weight [BW] dissolved in 1 mL of saline) daily for 10 consecutive days. CP-treated animals were administered a single intraperitoneal dose (7.5 mg/kg BW). Finally, a bilberry+CP group received oral bilberry extract (200 mg/kg BW) daily for 10 consecutive days, with one intraperitoneal dose of CP (7.5 mg/kg BW) on day 2. We assessed sperm count, motility, viability, and abnormalities, along with testis weight, testis weight-to-BW ratio, antioxidant activity, levels of oxidative stress markers (malondialdehyde [MDA] and hydrogen peroxide [H2O2]), sex hormones (follicle-stimulating hormone [FSH], luteinizing hormone [LH], and testosterone), and apoptotic and anti-apoptotic markers, and DNA damage. Testicular tissue underwent histopathological examination. Results: Among CP-treated rats, significantly lower values were observed for testis weight; testis weight-to-BW ratio; levels of FSH, LH, testosterone, superoxide dismutase, catalase, glutathione S-transferase, glutathione, and B-cell lymphoma 2; and sperm count, motility, and proportion of normal sperm. CP administration was associated with higher MDA, H2O2, p53, Bax, cytochrome c, caspase 9, and caspase 3 levels, along with elevated tail moment. However, bilberry extract administration significantly improved all altered parameters. Conclusion: Bilberry treatment demonstrated protective effects and reduced CP-induced testicular toxicity via antioxidant activity and cytoprotection. [ABSTRACT FROM AUTHOR]

Benzo[a]pyrene (BaP) is a contaminant that is generated in the environment through processes such as smoke, incomplete combustion of fossil fuels, vehicle exhaust emissions, entry into the body is through inhalation, and consumption of contaminated food. It is an omnipresent environmental pollutant with unavoidable exposure. BaP metabolites are observed in the male reproductive system, especially in the testes and epididymis of animals, and are responsible for reduced testicular and epididymal function. The protective effect of atorvastatin (ATV) on testicular damage was investigated previously. The aim of the present study was to investigate the protective effect of ATV on testicular toxicity induced by benzo[a]pyrene (BaP) during pregnancy in Wistar rats. This experimental laboratory study involved 40 adult rats, divided into seven groups and maintained under standard environmental conditions. The groups received different diets [control, corn oil, ATV (10 mg/kg), BaP (10 and 20 mg/kg), and ATV + BaP (10 and 20 mg/kg)] at gestation Days 7–16, orally. Male offspring were examined 10 weeks after birth. Testis and serum samples were collected, and testosterone level, malondialdehyde (MDA), and glutathione (GSH) were measured. Histological and immunohistochemical assays were performed under a light microscope. Statistical analysis was conducted using SPSS, with analysis of variance and Tukey tests to assess significant differences between groups. ATV significantly reduced MDA, a marker of lipid peroxidation and oxidative stress in rat testes following BaP administration. Treatment with ATV at doses of 10 mg/kg increased GSH levels, correcting disruptions in the antioxidant system caused by BaP. Testosterone concentration in rats treated with ATV and BaP substantially prevented the decrease induced by BaP. Histomorphometry revealed that ATV significantly prevented the detrimental effects of BaP on the thickness of spermatogenic epithelium and the diameter of seminiferous tubules. Under ATV treatment, testicular tissue histopathology improved, and spermatogenesis returned to a almost back to normal state. Caspase‐3 expression decreased, and apoptosis activity in testicular tissue improved under ATV treatment, indicating a positive effect of ATV in reducing apoptotic damage caused by BaP. In conclusion, exposure to BaP can induce oxidative stress‐related damage to testicular tissue, as evidenced by an increase in MDA levels, which ATV treatment can mitigate. Additionally, ATV enhances intracellular antioxidant GSH and protects the testes against BaP‐induced damage while increasing testosterone levels, which are reduced due to exposure to BaP. [ABSTRACT FROM AUTHOR]

Abstract Recently, it was reported that a testicular organ culture system (TOCS) using polydimethylsiloxane (PDMS) chips with excellent oxygen permeability and biocompatibility, called the PDMS-chip ceiling (PC) method, enables improved spermatogenesis efficiency. We investigated whether this PC method is useful for detecting impaired spermatogenesis caused by busulfan (Bu), a typical testicular toxicant. In this study, testicular tissue fragments from Acro3-EGFP mice, which express the green fluorescent protein (GFP) and reflect the progression of spermatogenesis, were subjected to the PC method. When treated with Bu, cultured tissues shrank in volume, and their GFP-expressing area decreased or disappeared. Histological examination confirmed the regression of spermatogenesis. In addition, immunohistochemical examination revealed that spermatogonia, including spermatogonial stem cells (SSCs), were the primary targets of Bu toxicity. Time-course analysis demonstrated that the recovery of spermatogenesis, dependent on Bu concentration, correlated closely with the severity of damage to these target cells. These results suggest that the PC method is a useful approach for detecting spermatogenesis impairment accurately through faithful recapitulation of spermatogenesis in vivo.

Objective(s): In recent years, microplastics (MPs), which are novel environmental contaminants measuring 5 mm in diameter, have garnered considerable attention. However, information regarding substances that can mitigate the dangers of MPs for animals remains extremely limited. Materials and Methods: Ninety days were devoted to the exposure of mature male mice to royal jelly (RJ) and 2 µm virgin polystyrene microplastics (PS-MPs) in this study. Pre-implantation embryo development; the structure of testis tissue; the gonadosomatic index; sperm parameters; RNA damage in germinal cells; the anti-oxidant capacity of the entire testis; and the activity of anti-oxidant enzymes in serum and testicular tissue, including TAC, SOD dismutase, CAT, GSH, and MDA, histomorphometric indices of the testis (tubular differentiation index, spermatogenesis index, and repopulation index), steroidogenic foci, and the quantity of apoptosis were assessed in the testis, respectively, through the measurement of pro-apoptosis (p53, Bax, and Caspase-3) and anti-apoptosis (Bcl-2) factors, as well as Hsp70 mediator. Results: The results indicate that concurrent administration of RJ can confer a protective effect on mice exposed to microplastics by maintaining the structure of mitochondria and enhancement of the anti-oxidant defense system. Furthermore, RJ co-treatment decreased apoptosis and oxidant/anti-oxidant status, enhanced pre-implantation embryo development, and improved sperm characteristics and RNA damage in germ cells. Conclusion: The data confirm that royal jelly could protect the testis structure against polystyrene microplastic-induced testicular injury through anti-oxidant and anti-apoptotic properties. [ABSTRACT FROM AUTHOR]

Recent research in rodents suggests that oxidative stress, inflammation, and apoptosis in the testes caused by high-fat diets (HFD) are a cause of male infertility. To investigate the therapeutic efficacy of the combination of hydroxycitric acid and capsaicin (HCC) against male reproductive disorders, we developed an HFD-induced obese rat model. Rats received HFD supplementation for 21 weeks, which induced obesity. From week 16, HCC (100 mg/kg body weight) was administered to investigate its potential to treat testicular toxicity. According to the results of the current study, treatment of obese rats with HCC improved their sperm quality, increased the production of testosterone, follicle-stimulating hormone, and luteinizing hormone and significantly increased the activities of steroidogenic enzymes and corresponding mRNA levels. In addition, HCC decreased lipid peroxidation and nitric oxide levels in both spermatozoa and testes while increasing the expression of mRNA for the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in the testes, which in turn reduced oxidative stress in the testes. Moreover, after HCC treatment, testicular tissues showed a remarkable decrease in mRNA levels responsible for inflammation (TNF-α, IL-6, NF-κB) and apoptosis (Bax and Bcl-2). Our results suggest that HCC may alleviate obesity-induced male reproductive dysfunction by attenuating oxidative stress, inflammation, and apoptosis in the testes of HFD-induced obese male rats. [ABSTRACT FROM AUTHOR]

Paraquat (PQ) is a noxious herbicide which adversely affects the vital organs including male reproductive system. Sudachitin (SCN) is a naturally occurring flavonoid that demonstrates a wide range of biological potentials. The current study was designed to investigate the alleviative potential of SCN to avert PQ‐induced testicular toxicity in rats. Forty‐eight male rats (Rattus norvegicus) were apportioned into four groups including control, PQ (5 mg/kg), PQ + SCN (5 mg/kg + 30 mg/kg), and SCN (30 mg/kg) only treated group. Our findings elucidated that PQ treatment reduced the expression of nuclear factor erythroid 2‐related factor 2 (Nrf‐2) and its antioxidant genes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR) and glutathione peroxidase (GPx), while elevating the levels of reactive oxygen species (ROS), and malondialdehyde (MDA). Furthermore, PQ intoxication upregulated the expressions of Keap‐1 while downregulating the expression of 3‐beta hydroxysteroid dehydrogenase (3β‐HSD), 17‐beta hydroxysteroid dehydrogenase (17β‐HSD), and steroidogenic acute regulatory protein (StAR). Moreover, sperm anomalies were increased following the exposure to PQ. Besides, PQ exposure decreased the levels of plasma testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) while increasing the levels of interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), nuclear factor‐kappa B (NF‐κB), interleukin‐1beta (IL‐1β), and cyclooxygenase‐2 (COX‐2). Additionally, PQ treatment escalated the expressions of cysteinyl aspartate‐specific proteases‐3 (Caspase‐3) and Bcl‐2‐associated X‐protein (Bax) while downregulating the expressions of B‐cell lymphoma‐2 (Bcl‐2). Furthermore, PQ exposure disrupted the normal architecture of testicular tissues. However, SCN treatment remarkably protected the testicular tissues via regulating the aforementioned disruptions owing to its antioxidant, anti‐inflammatory, and androgenic potential. [ABSTRACT FROM AUTHOR]

Abstract Cyclophosphamide (CTX) is the most commonly used effective alkylating drug in cancer treatment, but its use is restricted because its toxic side effect causes testicular toxicity. CTX disrupts the tissue redox and antioxidant balance and the resulting tissue damage causes oxidative stress. In our study based on this problem, kefir against CTX-induced oxidative stress and testicular toxicity were investigated. Rats were divided into 6 groups: control, 150 mg/kg CTX, 5 and 10 mg/kg kefir, 5 and 10 mg/kg kefir + 150 CTX. While the fermented kefirs were mixed and given to the rats for 12 days, CTX was given as a single dose on the 12th day of the experiment. Testis was scored according to spermatid density, giant cell formation, cells shed into tubules, maturation disorder, and atrophy. According to our biochemical findings, the high levels of total oxidant status (TOS), and the low levels of total antioxidant status (TAS) in the CTX group, which are oxidative stress markers, indicate the toxic effect of CTX, while the decrease in TOS levels and the increase in TAS levels in the kefir groups indicate the protective effect of kefir. In the CTX-administered group, tubules with impaired maturation and no spermatids were observed in the transverse section of the testicle, while in the kefir groups, the presence of near-normal tubule structures and tubule lumens despite CTX showed the protective effect of kefir. In our study, it was observed that kefir had a protective and curative effect on CTX-induced toxicity and oxidative stress and could be a strong protector.

Background: Thioacetamide (TAA) is known to cause damage to various organs, including the testes, posing a significant health threat. On the other hand, Curcuma longa (Cl) has been recognized for its antioxidant properties, suggesting a potential protective role against TAA-induced toxicity in the testes. Aim: This study aims to investigate the effect of TAA on testicular function and structure while exploring the therapeutic and protective potential of C. longa versus TAA toxicity. Methods: Thirty-two male albino rats, with an age range of 11–12 weeks and a weight range of 180-200 g, were randomly allocated into four distinct groups. The control group received normal saline, while the Cl group ingested Cl orally at a dose of 500 mg/kg daily. The TAA group, received TAA through intraperitoneal injections at a dose of 200 mg/kg body weight three times per week. Lastly, the Cl with TAA group received Cl orally 2 hours before the TAA injections. After 8 weeks of treatment, we anesthetized the rats and saved blood samples for biochemical analysis. Results: The study revealed significant alterations in various biochemical parameters in the TAA-treated group, as compared with the control. Specifically, there was a significant increase in bilirubin, albumin, cholesterol, triglyceride, very low-density lipoprotein (VLDL-C), white blood cells (WBCs), low-density lipoprotein cholesterol (LDL-C), and platelets (PLT) levels. Conversely, the Cl-treated group exhibited significant reductions in these parameters, along with notable increases in red blood cells (RBCs), high-density lipoprotein cholesterol (HDL-C), and hemoglobin (HB). Conclusion: C. longa demonstrates a protective effect on the testes against TAA-induced toxicity, potentially attributed to its antioxidant properties. This suggests a promising avenue for the use of Cl in mitigating the harmful effects of TAA on testicular function and structure. [Open Vet J 2024; 14(7.000): 1585-1595]

Introduction: Hydroxychloroquine (HCQ) is a medicine that has mainly been used to treat malaria. During the recent Coronavirus Disease-2019 (COVID-19) period, an abrupt spike in the sale of HCQ has been found. The repurposing of this drug in the treatment of COVID-19 was not only found to be ineffective but also showed many side effects. The adverse effects of the enormous exposure to this drug should be unveiled. Aim: To evaluate the acute effect of HCQ exposure on the male reproductive system by analysing the changes in antioxidant enzyme levels in testicular tissue, sperm quality, and histopathological assessment of testicular tissue using male albino rats as the subject model. Materials and Methods: The present experimental study was done by using male albino rats as the subject model. It was conducted in the laboratory of the Department of Human Physiology at Raja NL Khan Women’s College (Autonomous) in Medinipur, West Bengal, Kolkata, India, from the last week of June 2023 to the first week of August 2023. A total 10 male albino rats were obtained and randomly divided into two groups (n=5 in each group), control and HCQ-treated, and were given plain drinking water and 33 mg/kg/day HCQ, respectively, for six consecutive days through oral gavage. After the treatment tenures, rats were euthanised, and antioxidant enzymatic activity was measured by a spectrophotometer. Sperm quality and testicular histopathology were studied. A two-tailed t-test was used to compare the parameters of the control and HCQ-treated groups. Results: The total testicular weight of the control group was 2.37±0.17 g, in contrast treated group had a significantly lower testicular weight of 1.98±0.19 g. A significant decrease in total testicular protein in the treated group was found, i.e., 28.86±3.03 mg/g of tissue, compared to the control group, i.e., 60.46±2.85 mg/g of tissue. The sperm count of the control group was 4.51±0.06 million/ml of suspension, while the treated group had a significantly lower sperm count, i.e., 2.73±0.11 million/mL of suspension. The percentages of sperm motility and viability in the control group were 86±1.63% and 94±1.33%, respectively, but in the treated group, the percentages were significantly lower, i.e., 22.66±1.35% and 24±1.78%, respectively. The increasing sperm anomalies after HCQ exposure indicate poor sperm quality. Conclusion: Infertility or reduced fertility can result from testicular dysfunction, in continuation, decrease in sperm count, motility, viability, together with abnormalities in sperm morphology, was observed after this exposure. Thus, the present study provides insight into the adverse effects of the use of this drug, which might be associated with male infertility.

Cyclophosphamide (CTX) is the most commonly used effective alkylating drug in cancer treatment, but its use is restricted because its toxic side effect causes testicular toxicity. CTX disrupts the tissue redox and antioxidant balance and the resulting tissue damage causes oxidative stress. In our study based on this problem, kefir against CTX-induced oxidative stress and testicular toxicity were investigated. Rats were divided into 6 groups: control, 150 mg/kg CTX, 5 and 10 mg/kg kefir, 5 and 10 mg/kg kefir + 150 CTX. While the fermented kefirs were mixed and given to the rats for 12 days, CTX was given as a single dose on the 12th day of the experiment. Testis was scored according to spermatid density, giant cell formation, cells shed into tubules, maturation disorder, and atrophy. According to our biochemical findings, the high levels of total oxidant status (TOS), and the low levels of total antioxidant status (TAS) in the CTX group, which are oxidative stress markers, indicate the toxic effect of CTX, while the decrease in TOS levels and the increase in TAS levels in the kefir groups indicate the protective effect of kefir. In the CTX-administered group, tubules with impaired maturation and no spermatids were observed in the transverse section of the testicle, while in the kefir groups, the presence of near-normal tubule structures and tubule lumens despite CTX showed the protective effect of kefir. In our study, it was observed that kefir had a protective and curative effect on CTX-induced toxicity and oxidative stress and could be a strong protector. [ABSTRACT FROM AUTHOR]

Background: Thioacetamide (TAA) is known to cause damage to various organs, including the testes, posing a significant health threat. On the other hand, Curcuma longa (Cl) has been recognized for its antioxidant properties, suggesting a potential protective role against TAA-induced toxicity in the testes. Aim: This study aims to investigate the effect of TAA on testicular function and structure while exploring the therapeutic and protective potential of C. longa versus TAA toxicity. Methods: Thirty-two male albino rats, with an age range of 11-12 weeks and a weight range of 180-200 g, were randomly allocated into four distinct groups. The control group received normal saline, while the Cl group ingested Cl orally at a dose of 500 mg/kg daily. The TAA group, received TAA through intraperitoneal injections at a dose of 200 mg/kg body weight three times per week. Lastly, the Cl with TAA group received Cl orally 2 hours before the TAA injections. After 8 weeks of treatment, we anesthetized the rats and saved blood samples for biochemical analysis. Results: The study revealed significant alterations in various biochemical parameters in the TAA-treated group, as compared with the control. Specifically, there was a significant increase in bilirubin, albumin, cholesterol, triglyceride, very low-density lipoprotein, white blood cells, low-density lipoprotein cholesterol, and platelets levels. Conversely, the Cl-treated group exhibited significant reductions in these parameters, along with notable increases in red blood cells, high-density lipoprotein cholesterol, and hemoglobin. Conclusion: C. longa demonstrates a protective effect on the testes against TAA-induced toxicity, potentially attributed to its antioxidant properties. This suggests a promising avenue for the use of Cl in mitigating the harmful effects of TAA on testicular function and structure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Hydroxychloroquine (HCQ) is a medicine that has mainly been used to treat malaria. During the recent Coronavirus Disease-2019 (COVID-19) period, an abrupt spike in the sale of HCQ has been found. The repurposing of this drug in the treatment of COVID-19 was not only found to be ineffective but also showed many side effects. The adverse effects of the enormous exposure to this drug should be unveiled. Aim: To evaluate the acute effect of HCQ exposure on the male reproductive system by analysing the changes in antioxidant enzyme levels in testicular tissue, sperm quality, and histopathological assessment of testicular tissue using male albino rats as the subject model. Materials and Methods: The present experimental study was done by using male albino rats as the subject model. It was conducted in the laboratory of the Department of Human Physiology at Raja NL Khan Women’s College (Autonomous) in Medinipur, West Bengal, Kolkata, India, from the last week of June 2023 to the first week of August 2023. A total 10 male albino rats were obtained and randomly divided into two groups (n=5 in each group), control and HCQ-treated, and were given plain drinking water and 33 mg/kg/day HCQ, respectively, for six consecutive days through oral gavage. After the treatment tenures, rats were euthanised, and antioxidant enzymatic activity was measured by a spectrophotometer. Sperm quality and testicular histopathology were studied. A two-tailed t-test was used to compare the parameters of the control and HCQ-treated groups. Results: The total testicular weight of the control group was 2.37±0.17 g, in contrast treated group had a significantly lower testicular weight of 1.98±0.19 g. A significant decrease in total testicular protein in the treated group was found, i.e., 28.86±3.03 mg/g of tissue, compared to the control group, i.e., 60.46±2.85 mg/g of tissue. The sperm count of the control group was 4.51±0.06 million/ml of suspension, while the treated group had a significantly lower sperm count, i.e., 2.73±0.11 million/mL of suspension. The percentages of sperm motility and viability in the control group were 86±1.63% and 94±1.33%, respectively, but in the treated group, the percentages were significantly lower, i.e., 22.66±1.35% and 24±1.78%, respectively. The increasing sperm anomalies after HCQ exposure indicate poor sperm quality. Conclusion: Infertility or reduced fertility can result from testicular dysfunction, in continuation, decrease in sperm count, motility, viability, together with abnormalities in sperm morphology, was observed after this exposure. Thus, the present study provides insight into the adverse effects of the use of this drug, which might be associated with male infertility. [ABSTRACT FROM AUTHOR]

MDMA (3,4-methylenedioxymethamphetamine) and tramadol are central nervous system stimulants known for inducing emotional communion and socializing effects. FMRFamide, an RFamide peptide isolated from mollusks, plays diverse roles in physiological processes. This study aimed to evaluate FMRFamide's impact on testicular toxicity induced by MDMA/tramadol in Wistar rats. Thirty male Wistar rats were divided into six groups (n=5). Group A served as the control, Group B received 2 mg/kg FMRFamide for two consecutive days. Groups C, D, and E received MDMA/tramadol (20 mg/kg) for ten days, while Group F received the same dosage along with FMRFamide. Sperm analysis, biochemical, and histological assessments were conducted. The results revealed significant body weight loss, decreased sperm count and motility, increased abnormal sperm formation, and reduced serum LH, FSH, and Testosterone levels. Inducible Nitric Oxide Synthase (iNOS) expression was intensified in Groups A, B, D, and F. Notably, FMRFamide administration attenuated the adverse effects of MDMA/tramadolinduced testicular toxicity, suggesting a potential therapeutic role in safeguarding male reproductive health. These findings highlight the importance of further exploring FMRFamide's protective mechanisms and its potential application in mitigating drug-induced reproductive toxicity. [ABSTRACT FROM AUTHOR]

Background: Nanoplastics can be considered a novel contaminant for the environment because of their extensive applications in modern society, which represents a possible threat to humans. Nevertheless, the negative effect of polystyrene nanoplastics (PS‐NPs) on male reproduction, fertility, and progeny outcomes is not well known. Thus, the aim of the present work was to calculate the median lethal dose (LD50) and investigate the consequences of exposure to PS‐NPs (25 nm) on male reproductive toxicity. Methods: This investigation first determined the LD50 of PS‐NPs in male Wistar rats, and then in a formal study, 24 rats were distributed into three groups (n = 8): the control group; the low‐dose group (3 mg/kg bw); and the high‐dose group (10 mg/kg bw) of PS‐NPs administered orally for 60 days. On the 50th day of administration, the fertility test was conducted. Results: The LD50 was determined to be 2500 mg/kg. PS‐NP administration induced significant alternations, mainly indicating mortality in the high‐dose group, a significant elevation in body weight gain, declined sperm quality parameters, altered reproductive hormonal levels, thyroid endocrine disruption, an alternation of the normal histo‐architecture and the histo‐morphometric analysis of the testes, and impaired male fertility. Conclusion: Altogether, the current findings provide novel perspectives on PS‐NP general toxicity with specific reference to male reproductive toxicity. [ABSTRACT FROM AUTHOR]

Objective(s): Male infertility is a major public health issue due to increased prevalence, so there is an urgent need for a therapeutic solution. The search for a natural dietary substance that could modulate redox balance and inflammation and protect testicular function is in demand. Virgin Coconut Oil (VCO) has found use in the treatment of diabetes, and cancer owing to the presence of polyphenols. However, there is a dearth of information on its effect on testicular toxicity. The present study investigated VCO as a possible treatment for testicular toxicity in the Sodium Benzoate (SB) model of male infertility by evaluating the oxidative and inflammatory status, circulating hormonal levels, and key sperm indices.Materials and Methods: Twenty adult male rats were randomly assigned to four groups of 5 rats each and were treated with normal saline, sodium benzoate, sodium benzoate+5% VCO, and sodium benzoate+15% VCO for 30 days respectively. Biochemical analysis of reproductive hormones was assessed. Sperm parameters assessed include sperm function tests and sperm kinematics. One-way analysis of variance (ANOVA) followed by post hoc Tukey tests was performed.Results: 5% VCO reverts the deranged serum reproductive hormones caused by sodium benzoate. 5% VCO was more potent as an antioxidant and anti-inflammatory treatment than 15% VCO. However, both doses prevented SB’s effect on the sperm function test and kinematics.Conclusion: VCO-supplemented diet can ameliorate SB-induced testicular toxicity by inhibiting its mechanisms of toxicity that are related to oxidative stress, apoptosis, and inflammation.

Objective(s): This study aimed to investigate the effects of zingerone (ZNG) treatment on testicular toxicity in rats induced by sodium arsenite (SA).Materials and Methods: In the study, five groups were formed (n=7) and the experimental groups were designated as follows; Vehicle group, ZNG group, SA group, SA+ZNG 25 group, and SA+ZNG 50 group. While SA was administered orally to rats at 10 mg/kg/bw, ZNG was given to rats orally at 25 and 50 mg/kg/bw doses for 14 days.Results: As a result of the presented study, an increase was observed in the MDA contents of the testicular tissue of the rats administered SA, while significant decreases were observed in GSH levels, SOD, CAT, and GPx activities. The mRNA transcript levels of the pro-inflammatory genes NF-κB, TNF-α, IL-1β, and IL-6 were triggered after SA administration. Additionally, SA administration caused inflammation by increasing RAGE, NLRP3, and JAK-2/STAT3 gene expression. Moreover, endoplasmic reticulum (ER) stress occurred in the testicular tissues of SA-treated rats and thus ATF-6, PERK, IRE1, and GRP78 genes were up-regulated. SA caused apoptosis by up-regulating Bax and Caspase-3 expressions and inhibiting Bcl-2 expression in testicles. SA caused histological irregularities in the testicles, resulting in decreased sperm quality.Conclusion: ZNG treatment reduced SA-induced oxidative stress, ER stress, inflammation, apoptosis, and histological irregularities in the testicles while increasing sperm quality. As a result, it was observed that ZNG could alleviate the toxicity caused by SA in the testicles.

Objective(s): Oxaliplatin (OXL) is a platinum-based chemotherapeutic agent widely used in the treatment of colorectal cancer. Unfortunately, this important drug also causes unwanted side effects such as neuropathy, ototoxicity, and testicular toxicity. This study aimed to investigate the possible protective effects of naringin (NRG) against OXL-induced testicular toxicity in rats. Materials and Methods: In the present study, rats were injected with OXL (4 mg/kg, b.w./day, IP) in 5% dextrose solution 30 min after oral administration of NRG (50 and 100 mg/kg, b.w./day) on the 1st, 2nd, 5th, and 6th days. Then, the rats were sacrificed on the 7th day and the testicular tissues were removed. Results: The results showed that NRG decreased (P

Cyclophosphamide is one of the most invasive chemotherapeutic drugs, which is commonly used despite its adverse effects and toxicities. Scutellarin is an herbal flavonoid with multiple pharmacological activities and clinical applications. The goal of the current study was to investigate whether scutellarin protected the gonads of male rats exposed to a single dose of cyclophosphamide. In the experiment, 21 male Sprague-Dawley male rats were divided into three groups (n=7/group). Control group; received normal saline for 12 days by mouth; Induction group; received normal saline for 12 days by mouth and a single dose of cyclophosphamide (100 mg/kg) intraperitoneally on day 6; and Scutellarin group; received intragastric scutellarin (100mg/kg) for 12 days and a single dose of cyclophosphamide (100mg/kg) intraperitoneally on day 6. At the end of treatment, the samples were collected, the gonadosomatic index (GSI) was calculated, sperm parameters, serum testosterone, testicular malondialdehyde (MDA), and glutathione peroxidase (GPx) levels were measured, and histopathological alternation was evaluated. The results showed that GSI, sperm parameters, testosterone, and GPx levels were notably declined, while the level of MDA was significantly higher in the induction group compared to the control group. Interestingly, these measures markedly improved in scutellarin treated group. Additionally, histopathological analysis revealed a substantial change in the testicular tissue structure and a decrease in Jonson's score in the induction group, although scutellarin co-treatment considerably attenuated and even reversed these changes. In conclusion, the outcomes demonstrated that scutellarin may act as a protective agent that alleviates rats' testicular toxicity caused by cyclophosphamide therapy. Further, the proposed process may be attributed to its potent antioxidant properties. [ J Adv Biotechnol Exp Ther 2024; 7(3.000): 572-585]

ABSTRACTBackground: Acrylamide is a toxic substance formed in some foods that require high-temperature cooking processes and has been implicated as a gonadotoxic agent. Zinc, on the other hand, is a known antioxidant with fertility-enhancing properties. Hence, this study was designed to explore the possible ameliorative effect of zinc in acrylamide-induced gonadotoxicity.Methods: Twenty-four male Wistar rats were randomized into control, acrylamide (10 mg/kg of acrylamide), acrylamide + 1 mg/kg of zinc, and acrylamide + 3 mg/kg of zinc. The administration was via the oral route and lasted for 56 days.Results: Zinc treatment ameliorated acrylamide-impaired sperm quality, normal testicular histoarchitecture, and hormonal balance, which was accompanied by increased testicular malondialdehyde and interleukin-1β and decreased testicular superoxide dismutase (SOD) and catalase (CAT). Furthermore, zinc prevented acrylamide-induced downregulation of testicular nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and B-cell lymphoma 2 (BCl2) expression and upregulation of testicular nuclear factor kappa B (NF-κB) and bcl-2-like protein 4 (bax) expression.Conclusion: In conclusion, zinc may protect against acrylamide-induced testicular toxicity, mediated by its antioxidant, anti-inflammatory, and antiapoptotic effects.

Objective(s): This study aimed to investigate the effects of zingerone (ZNG) treatment on testicular toxicity in rats induced by sodium arsenite (SA). Materials and Methods: In the study, five groups were formed (n=7) and the experimental groups were designated as follows; Vehicle group, ZNG group, SA group, SA+ZNG 25 group, and SA+ZNG 50 group. While SA was administered orally to rats at 10 mg/kg/bw, ZNG was given to rats orally at 25 and 50 mg/kg/bw doses for 14 days. Results: As a result of the presented study, an increase was observed in the MDA contents of the testicular tissue of the rats administered SA, while significant decreases were observed in GSH levels, SOD, CAT, and GPx activities. The mRNA transcript levels of the pro-inflammatory genes NF-κB, TNF-α, IL-1β, and IL-6 were triggered after SA administration. Additionally, SA administration caused inflammation by increasing RAGE, NLRP3, and JAK-2/STAT3 gene expression. Moreover, endoplasmic reticulum (ER) stress occurred in the testicular tissues of SA-treated rats and thus ATF-6, PERK, IRE1, and GRP78 genes were up-regulated. SA caused apoptosis by up-regulating Bax and Caspase-3 expressions and inhibiting Bcl-2 expression in testicles. SA caused histological irregularities in the testicles, resulting in decreased sperm quality. Conclusion: ZNG treatment reduced SA-induced oxidative stress, ER stress, inflammation, apoptosis, and histological irregularities in the testicles while increasing sperm quality. As a result, it was observed that ZNG could alleviate the toxicity caused by SA in the testicles. [ABSTRACT FROM AUTHOR]

Objective(s): Male infertility is a major public health issue due to increased prevalence, so there is an urgent need for a therapeutic solution. The search for a natural dietary substance that could modulate redox balance and inflammation and protect testicular function is in demand. Virgin Coconut Oil (VCO) has found use in the treatment of diabetes, and cancer owing to the presence of polyphenols. However, there is a dearth of information on its effect on testicular toxicity. The present study investigated VCO as a possible treatment for testicular toxicity in the Sodium Benzoate (SB) model of male infertility by evaluating the oxidative and inflammatory status, circulating hormonal levels, and key sperm indices. Materials and Methods: Twenty adult male rats were randomly assigned to four groups of 5 rats each and were treated with normal saline, sodium benzoate, sodium benzoate+5% VCO, and sodium benzoate+15% VCO for 30 days respectively. Biochemical analysis of reproductive hormones was assessed. Sperm parameters assessed include sperm function tests and sperm kinematics. One-way analysis of variance (ANOVA) followed by post hoc Tukey tests was performed. Results: 5% VCO reverts the deranged serum reproductive hormones caused by sodium benzoate. 5% VCO was more potent as an antioxidant and anti-inflammatory treatment than 15% VCO. However, both doses prevented SB's effect on the sperm function test and kinematics. Conclusion: VCO-supplemented diet can ameliorate SB-induced testicular toxicity by inhibiting its mechanisms of toxicity that are related to oxidative stress, apoptosis, and inflammation. [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<0.05), following treatment with 2.25mg/kg body weight of lead acetate; suggesting a possible anti-fertility effect of lead in male Wistar rats. However, significantly lower values of mount, intromission, ejaculatory latencies and post ejaculatory interval and higher values of mount, intromission and ejaculatory frequencies were observed following the administration of the leaf extract of Craterispermum schweinfurthi at 250mg/kg, 500mg/kg and 750mg/kg body weight doses amongst groups 3, 4 and 5 rats compare to group 2 (2.25mg/kg Lead only) rats (p<0.05), indicating a possible mitigating effect of the extract against lead induced toxicity in male Wistar rats. Craterispermum schweinfurthi improves appetitive and precopulatory components of sexual behavior like sexual excitement, arousal and libido; indicating intense and sustained sexual activity. [ABSTRACT FROM AUTHOR]

Successful treatment of pediatric cancers often results in long‐term health complications, including potential effects on fertility. Therefore, assessing the male reproductive toxicity of anti‐cancer drug treatments and the potential for recovery is of paramount importance. However, in vivo evaluations are time‐intensive and require large numbers of animals. To overcome these constraints, we utilized an innovative organ culture system that supports long‐term spermatogenesis by placing the testis tissue between a base agarose gel and a polydimethylsiloxane ceiling, effectively mirroring the in vivo testicular environment. The present study aimed to determine the efficacy of this organ culture system for accurately assessing testicular toxicity induced by cisplatin, using acrosin‐green fluorescent protein (GFP) transgenic neonatal mouse testes. The testis fragments were treated with different concentrations of cisplatin‐containing medium for 24 h and incubated in fresh medium for up to 70 days. The changes in tissue volume and GFP fluorescence over time were evaluated to monitor the progression of spermatogenesis, in addition to the corresponding histopathology. Cisplatin treatment caused tissue volume shrinkage and reduced GFP fluorescence in a concentration‐dependent manner. Recovery from testicular toxicity was also dependent on the concentration of cisplatin received. The results demonstrated that this novel in vitro system can be a faithful replacement for animal experiments to assess the testicular toxicity of anti‐cancer drugs and their reversibility, providing a useful method for drug development. Assessing the male reproductive toxicity of anti‐cancer drugs and the potential for recovery is of paramount importance; however, in vivo evaluations are time‐intensive and require large numbers of animals. We utilized an innovative organ culture system that mirrors the in vivo testicular environment to determine its efficacy in accurately assessing testicular toxicity induced by cisplatin. The results demonstrate that this system can be a faithful replacement for animal experiments to assess the testicular toxicity of anti‐cancer drugs and their reversibility. [ABSTRACT FROM AUTHOR]

AbstractThe human immunodeficiency virus continues to pose a significant global public health challenge, affecting millions of individuals. The current treatment strategy has incorporated the utilization of combinations of antiretroviral drugs. The administration of these drugs is associated with many deleterious consequences on several physiological systems, notably the reproductive system. This study aimed to assess the toxic effects of abacavir sulfate, ritonavir, nevirapine, and zidovudine, as well as their combinations, on TM3 Leydig and TM4 Sertoli cells. The cell viability was gauged using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and neutral red uptake (NRU) assays. Reactive oxygen species (ROS) production was assessed via the 2’,7’-dichlorofluorescein diacetate (DCFDA) test, and DNA damage was determined using the comet assay. Results indicated cytotoxic effects at low drug concentrations, both individually and combined. The administration of drugs, individually and in combination, resulted in the production of ROS and caused damage to the DNA at the tested concentrations. In conclusion, the results of this study suggest that the administration of antiretroviral drugs can lead to testicular toxicity by promoting the generation of ROS and DNA damage. Furthermore, it should be noted that the toxicity of antiretroviral drug combinations was shown to be higher compared to that of individual drugs. [ABSTRACT FROM AUTHOR]

Objective(s): Oxaliplatin (OXL) is a platinum-based chemotherapeutic agent widely used in the treatment of colorectal cancer. Unfortunately, this important drug also causes unwanted side effects such as neuropathy, ototoxicity, and testicular toxicity. This study aimed to investigate the possible protective effects of naringin (NRG) against OXL-induced testicular toxicity in rats. Materials and Methods: In the present study, rats were injected with OXL (4 mg/kg, b.w./day, IP) in 5% dextrose solution 30 min after oral administration of NRG (50 and 100 mg/kg, b.w./day) on the 1st, 2nd, 5th, and 6th days. Then, the rats were sacrificed on the 7th day and the testicular tissues were removed. Results: The results showed that NRG decreased (P<0.001) lipid peroxidation, increased (P<0.001) the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and the levels of glutathione (GSH), and also maintained the testis histological architecture and integrity. NRG decreased the levels of apoptosis-related markers such as caspase-3, Bax, and Apaf-1 and increased Bcl2 in the OXL-induced testicular toxicity (P<0.001). In addition, NRG reversed the changes in mRNA transcript levels of oxidative stress, inflammation, and endoplasmic reticulum stress parameters such as Nrf2, HO-1, NQO1, RAGE, NLRP3, MAPK-14, STAT3, NF-κB, IL-1β, TNF-α, PERK, IRE1, ATF6, and GRP78 in OXL-induced testicular toxicity (P<0.001). Conclusion: Our results demonstrated that NRG can protect against OXL-induced testicular toxicity by enhancing the anti-oxidant defense system and suppressing apoptosis, inflammation, and endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

The effects of Frl C60(OH)24, at different doses, on testicular tissue after Dox-induced toxicity in rats with colorectal cancer were investigated. In the present study, we used an in vivo Wistar male rat model to explore whether Frl could protect testicular tissue against Dox-induced chronic toxicity and compared the effect with a well-known antioxidant ascorbic acid. According to all results, we confirmed that, at all examined doses, Frl exhibits a protective role on the testicular tissue against chronic toxicity induced by Dox. [ABSTRACT FROM AUTHOR]

Acrylamide (ACR) is created when foods high in carbohydrates are heated up and is more harmful because it produces ROS inside cells. Our research aimed to investigate the potential of coenzyme Q10 (CoQ10) and rosuvastatin (ROSV) in mitigating the adverse effects of testicular toxicity induced by ACR in rats. A total of 49 male rats were distributed among 07 groups. Group 1 served as the control and was administered normal saline orally, while group 2 received oral CoQ10 at a dosage of 10 mg/kg BW; group 3, was administered ROSV (10 mg/kg/BW, orally); group 4, received ACR orally (20 mg/kg/BW); group 5 received ACR and CoQ10; group 6 administered ACR and ROSV; and group 7, the rats received ACR, CoQ10, and ROSV daily for 30 days. Acrylamide lowered serum testosterone, FSH, and LH levels, and marked elevations in testicular MDA levels were observed alongside notable decreases in GSH, CAT and SOD. It caused a significant reduction in the diameter of seminiferous tubules, numbers of spermatocytes, spermatogonia, Sertoli cells, germinal epithelium height, and a dramatic increase in lumen diameter. Also, the testicular histopathology was disturbed by ACR, and the testicular caspase-3 expression was considerably elevated in the ACR-treated group. In rats exposed to ACR intoxication, CoQ10 and ROSV raised levels of antioxidant biomarkers, lowered MDA and mitigated alterations in serum hormonal parameters. In summary, our results suggest that CoQ10 and ROSV exhibit considerable protective effects against ACR-induced testicular toxicity, attributed to their anti-oxidative properties. [ABSTRACT FROM AUTHOR]

The research aimed to investigate whether the combination of L-carnitine (LC) and thymoquinone (TQ) could lower the adverse effects of methotrexate (MTX), a widely used chemotherapy agent in cancer therapy, on testicular function. A total of seven groups were established (n=7); control group, LC (200 mg/kg PO), TQ (50 mg/kg PO), MTX (single IP dose of 20 mg/kg), LC+MTX, TQ+MTX, and LC+TQ+MTX. The use of MTX resulted in lower levels of testosterone, folliclestimulating hormone (FSH), and luteinizing hormone (LH) in the blood, accompanied by a significant rise in testicular MDA levels. Additionally, there was a notable decline in GSH, CAT, and SOD, indicating reduced antioxidant activity in the testicles. Furthermore, the histopathological examination of the testicles revealed disruptions caused by MTX, and the expression of caspase-3 in the testicles was documented. The combination of LC and TQ with MTX significantly increased testosterone, FSH, LD levels and restored oxidative damage markers (p<0.05) and improved histopathological scores and caspase-3 expression. In conclusion, our results demonstrate that LC and TQ exhibit substantial protective effects against testicular toxicity induced by MTX, primarily attributed to their antioxidant properties. [ABSTRACT FROM AUTHOR]

Introduction: Testicular damage is one of the most deleterious effects whenever cisplatin (CP) is employed in cancer treatment. CP results in male infertility. L-carnitine (LC) is a vitamin-like substance with antioxidant activity. L-carnitine improves spermatogenesis, sperm maturation and motility. Aim of the Work: Assess the protective role of LC in cisplatin-induced testicular toxicity. Material and Methods: Forty adult male albino rats (200-250 grams each) were divided into four groups. The first group is control. Group II: LC was intraperitoneal (IP) injected (500 mg/kg/d) for fifteen days. Group III: CP was injected with only one dose of 7 mg/kg CP (IP) on the 6th day. Group IV: LC plus CP received treatment of both groups II and III. Semen analysis was performed to estimate sperm count and motility. Testicular sections were examined under light microscopy using H&E, PAS, and anti-inducible nitric oxide synthase (iNOS) stainings. A transmission electron microscope was also done. Results: Cisplatin caused a significant decline in the body weight, absolute and relative testicular weight, sperm count, sperm motility, seminiferous tubular diameter, and germinal lining height in relation to other groups, with a significant improvement in the CP plus LC group. Specimens from CP-treated animals showed thick and destructed seminiferous tubules (ST) basal lamina, obvious disorganized and atrophied ST, spermatogenic arrest, and atrophied Leydig cells. LC improves these changes with variable preservation of spermatogenic cells. Inducible NOS staining in the CP-treated group showed a moderate positive reaction, other groups showed a negative or weak reaction. Transmission electron photomicrography of the CP group showed large cytoplasmic vacuoles, small distorted mitochondria, and large lipid droplets in most spermatogonic cells; abnormally shaped spermatozoa. Conclusion: L-carnitine partially attenuates CP-related histological changes of the testicular tissue and improves the quality parameters of the sperm, ensuring the protective effect of LC. [ABSTRACT FROM AUTHOR]

Bisphenol AF (BPAF), as one of structural analogs of BPA, has been increasingly used in recent years. However, limited studies have suggested its adverse effects similar to or higher than BPA. In order to explore the general toxicity and genotoxicity of subacute exposure to BPAF, the novel 28‐day multi‐endpoint (Pig‐a assay + micronucleus [MN] test + comet assay) genotoxicity evaluation platform was applied. Male rats were randomly distributed into seven main experimental groups and four satellite groups. The main experimental groups included BPAF‐treated groups (0.5, 5, and 50 μg/kg·bw/d), BPA group (10 μg/kg·bw/d), two solvent control groups (PBS and 0.1% ethanol/99.9% oil), and one positive control group (N‐ethyl‐N‐nitrosourea, 40 mg/kg bw). The satellite groups included BPAF high‐dose recovery group (BPAF‐HR), oil recovery group (oil‐R), ENU recovery group (ENU‐R), and PBS recovery group (PBS‐R). All groups received the agents orally via gavage for 28 consecutive days, and satellite groups were given a recovery period of 35 days. Among all histopathologically examined organs, testis and epididymis damage was noticed, which was further manifested as blood‐testis barrier (BTB) junction protein (Connexin 43 and Occludin) destruction. BPAF can induce micronucleus production and DNA damage, but the genotoxic injury can be repaired after the recovery period. The expression of DNA repair gene OGG1 was downregulated by BPAF. To summarize, under the design of this experiment, male reproductive toxicity of BPAF was noticed, which is similar to that of BPA, but its ability to induce micronucleus production may be stronger than that of BPA. In this study, we used the in vivo genotoxicity integrative evaluation system to evaluate the genotoxicity under subacute exposure to BPAF and explore and compare the mechanism of BPAF and BPA in inducing DNA damage and testicular damage. Under the design of this experiment, male reproductive toxicity of BPAF was noticed, which is similar to that of BPA, but its ability to induce micronucleus production may be stronger than that of BPA. [ABSTRACT FROM AUTHOR]

Objective: Bisphenol A (BPA) is a common environmental endocrine disruptor that negatively impairs male reproductive ability. This study aimed to explore the alterations in serum metabolomics that occur following BPA exposure and the mechanism via which BPA induces the death of testicular cells in a male mouse model. Methods: The mice were classified into two groups: BPA-exposed and control groups, and samples were collected for metabolomic determination, semen quality analysis, electron microscopy, enzyme-linked immunosorbent assay, quantitative real-time PCR, pathological staining, and Western blot analysis. Results: BPA exposure caused testicular damage and significantly decreased sperm quality in mice. Combined with non-target metabolomic analysis, this was closely related to ferroptosis induced by abnormal metabolites of arachidonic acid and phosphatidylcholine, and the expression of its related genes, acyl CoA synthetase 4, glutathione peroxidase 4, lysophosphatidylcholine acyltransferase 3, and phosphatidylethanolamine-binding protein 1 were altered. Conclusion: BPA induced ferroptosis, caused testicular damage, and reduced fertility by affecting lipid metabolism in male mice. Inhibiting ferroptosis may potentially function as a therapeutic strategy to mitigate the male reproductive toxicity induced by BPA.

Background and Aim: Doxorubicin (DOX) is often used as a chemotherapeutic agent, although it may damage testicular functions. This study was designed to investigate the protective effects of propolis on testicular histological changes, semen parameters, and testosterone concentrations as a means of protecting against testicular damage caused by DOX chemotherapy. Materials and Methods: Forty-eight male Wistar rats were divided into four groups with 12 animals per group. The first group served as the control. Rats in the second group were administered 4 mg/kg DOX. The third group was administered 4 mg/kg of DOX and 30 mg/kg b.w. propolis. The fourth group was orally dosed daily with 30 mg/kg b.w. propolis. Results: DOX treatment resulted in a significantly decreased weight gain (WG) rate compared with the control, whereas DOX + propolis resulted in improved WG and returned to the normal range. Testosterone levels were comparable among the experimental groups, with a significant increase in the propolis-treated group. In addition, DOX-treated groups exhibited a remarkable depletion in sperm counts, motility, and viability compared to the other groups. Conclusion: Most of the histological and hormonal changes resulting from the toxicity of DOX returned to almost normal after treatment of rats with the aqueous extract of propolis, indicating that propolis ameliorated the effects of DOX poisoning on testicular function in male rats.

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 5ml distilled water, and the Pb group was I.P injected with 20 mg/kg of lead acetate. Pb + Vit. E group received Pb with 100 mg/kg of vitamin E, Pb + KAF group received Pb with 50 mg/kg of kaempferol, Pb + KAF + Vit. E group received Pb with kaempferol and vitamin E for six weeks. Results: The testicular levels of superoxide dismutase, catalase, steroidogenic enzyme, serum testosterone, FSH, interleukin -10, and sperm function were significantly decreased in the Pb group compared with all experimental groups. These parameters were significantly elevated in Pb + KAF + Vit. E group compared to other experimental groups. Lead acetate caused elevation in testicular malondialdehyde, nitric oxide, interleukin-6, interleukin-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 + Vit. E group and Pb + KAF group compared with the Pb group. The fold changes of pituitary FSHβ, GnRHr, and LHβ, and testicular CYP11A1, LHr, and FHr gene expression were significantly upregulated in Pb + KAF + Vit. E group compared with all experimental groups. Additionally, KAF + Vit. E have the potential to improve the 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. [Open Vet J 2023; 13(12.000): 1683-1695]

The use of additives, especially colorants, in food and pharmaceutical industry is increasing dramatically. Currently, additives are classified as contaminants of emerging concern (CECs). Concerns have been raised about the potential hazards of food additives to reproductive organs and fertility. The present study investigates the reproductive toxicity of tartrazine (TRZ), a synthetic colorant, in male rats and aims to explore the curative effect of Ginkgo biloba extract (EGb) against TRZ-induced testicular toxicity. Twenty-four rats were divided into four groups: the control (0.5 ml distilled water), the EGb group (100 mg/kg EGb alone), the TRZ group (7.5 mg/kg TRZ alone), and the TRZ-EGb group (7.5 mg/kg TRZ plus 100 mg/kg EGb). The doses were administered orally in distilled water once daily for 28 days. Toxicity studies of TRZ investigated testicular redox state, serum gonadotropins, and testosterone levels, testicular 17 ß-hydroxysteroid dehydrogenase activity, sperm count and quality, levels of inflammatory cytokines, and caspase-3 expression as an apoptotic marker. Also, histopathological alterations of the testes were examined. TRZ significantly affected the testicular redox status as indicated by the increase in malondialdehyde and the decrease in reduced glutathione, superoxide dismutase, and catalase. It also disrupted serum gonadotropins (follicle stimulating hormone and luteinizing hormone) and testosterone levels and the activity of testicular 17ß-hydroxysteroid dehydrogenase. Additionally, TRZ adversely affected sperm count, motility, viability, and abnormality. Levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, and expression of caspase-3 were increased in the testes. Histopathological examination of the testes supported the alterations mentioned above. Administration of EGb significantly ameliorated TRZ-induced testicular toxicity in rats. In conclusion, EGb protected against TRZ-induced testicular toxicity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. [ABSTRACT FROM AUTHOR]

Background and Aim: Doxorubicin (DOX) is often used as a chemotherapeutic agent, although it may damage testicular functions. This study was designed to investigate the protective effects of propolis on testicular histological changes, semen parameters, and testosterone concentrations as a means of protecting against testicular damage caused by DOX chemotherapy. Materials and Methods: Forty-eight male Wistar rats were divided into four groups with 12 animals per group. The first group served as the control. Rats in the second group were administered 4 mg/kg DOX. The third group was administered 4 mg/kg of DOX and 30 mg/kg b.w. propolis. The fourth group was orally dosed daily with 30 mg/kg b. w. propolis. Results: DOX treatment resulted in a significantly decreased weight gain (WG) rate compared with the control, whereas DOX + propolis resulted in improved WG and returned to the normal range. Testosterone levels were comparable among the experimental groups, with a significant increase in the propolis-treated group. In addition, DOX-treated groups exhibited a remarkable depletion in sperm counts, motility, and viability compared to the other groups. Conclusion: Most of the histological and hormonal changes resulting from the toxicity of DOX returned to almost normal after treatment of rats with the aqueous extract of propolis, indicating that propolis ameliorated the effects of DOX poisoning on testicular function in male rats. [ABSTRACT FROM AUTHOR]

Antimicrobial agent resistance has become a growing health issue across the world. Colistin (COL) is one of the drugs used in the treatment of multidrug‐resistant bacteria resulting in toxic effects. Naringin (NRG), a natural flavonoid, has come to the fore as its antioxidant, anti‐inflammatory, and antiapoptotic activities. The aim of the present study was to determine whether NRG has protective effects on COL‐induced toxicity in testicular tissue. Thirty‐five male Spraque rats were randomly divided into five groups (n = 7 per group): Control, COL, NRG, COL + NRG 50, COL + NRG 100. COL (15 mg/kg b.w., i.p., once per/day), and NRG (50 or 100 mg/kg, oral, b.w./once per/day) were administered for 7 days. The parameters of oxidative stress, inflammation, apoptosis, and autophagic damage were evaluated by using biochemical, molecular, western blot, and histological methods in testicular issues. NRG treatment reversed the increased malondialdehyde level and reduced antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione) levels due to COL administration (p < 0.001), and oxidative stress damage was mitigated. Nuclear factor erythroid 2‐related factor‐2 pathway, one of the antioxidant defence systems, was stimulated by NRG (p < 0.001). NRG treatment reduced the levels of markers for the pathways of apoptotic (p < 0.001) and autophagic (p < 0.001) damages induced by COL. Sperm viability and the live/dead ratio were reduced by COL but enhanced by NRG treatment. Testicular tissue integrity was damaged by COL but showed a tendency to improve by NRG. In conclusion, COL exhibited toxic effect on testicular tissue by elevating the levels of oxidative stress, apoptosis, autophagy, inflammation, and tissue damage. NRG demonstrated a protective effect by alleviating toxic damage. Highlights: Colistin induces testicular toxicity.Naringin attenuates colistin‐induced oxidative stress.Naringin attenuates colistin‐induced inflammation.Naringin attenuates colistin‐induced apoptosis.Naringin attenuates colistin‐induced autophagy. [ABSTRACT FROM AUTHOR]

Polystyrene microplastics (PSMPs) have emerged as a ubiquitous environmental toxicant that affects different organs including testes. Ginkgetin (GNG) is a biflavonoid that shows antioxidant properties. The current research was undertaken to evaluate the ameliorative potential of GNG against PSMPs-instigated testicular damages. Forty-eight albino rats (male) were randomly divided into 4 equal groups: control, PSMPs-treated group (0.01 mgkg−1), GNG + PSMPs–exposed group (25 mgkg−1 + 0.01 mgkg−1), and only GNG-supplemented group (25 mgkg−1). After 56 days of treatment, it was revealed that PSMPs significantly reduced the activity of glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GSR), while concurrently augmented the levels of lipid peroxidation marker, i.e., malondialdehyde (MDA) along with reactive oxygen species (ROS). Rats administered with PSMPs showed a significant reduction in the spermatogenic indices (sperm count, viability, and motility), HOS coiled tail sperm along with increased sperm structural deformities, i.e., tail, head, and mid-piece. Additionally, PSMPs exposure decreased the levels of testosterone, luteinizing (LH), and follicle-stimulating hormones (FSH). Besides, administration of PSMPs reduced the steroidogenic enzymes (13β-HSD, StAR, and 17β-HSD) and Bcl-2 expression, while augmented the caspase-3 and Bax expression. PSMPs also elevated the levels of inflammatory markers (IL-6, IL-1β, TNF-α, and NF-κB) and activity of COX-2 in the testes. Furthermore, PSMPs treatment induced various histopathological damages in the testes of rats. Therefore, findings of the current study suggested that GNG effectively mitigated the PSMPs-induced testicular toxicity owing to its chemoprotective potential possibly through its anti-inflammatory, antioxidant, anti-apoptotic, and androgenic properties. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]