Jul 2026· Journal of Shahid Sadoughi University of Medical Sciences· 0 citations
TL;DR
It is shown that cyclophosphamide induces oxidative stress, causes disruption in the structure and function of the testis, and selenium reduced these damages and improved important histological and oxidative stress parameters to levels similar to the control group, suggesting a protective role against cyclophosphamide-induced testicular damage.
Abstract
Introduction: Cyclophosphamide, as a chemotherapeutic drug, causes induction of oxidative stress and disruption in the testis structure and function. In this study, the effect of selenium as a strong antioxidant on the testicular tissue of male mice after treatment with cyclophosphamide was evaluated.
Methods: For this experimental study, 32 adult male NMRI mice were divided into four groups of eight: control, cyclophosphamide (100 mg/kg, administered once weekly), selenium (1 mg/kg daily for 35 days), and a combination of cyclophosphamide and selenium. Following the 35-day treatment period, the mice were dissected; the left testis was utilized to measure malondialdehyde (MDA) levels and total antioxidant capacity (TAC), while the right testis, after undergoing fixation, tissue processing, sectioning, and hematoxylin-eosin staining, was employed for stereological analyses. Data were analyzed using SPSS software, applying one-way ANOVA followed by Tukey’s post-hoc test, with statistical significance set at p<0.05.
Results: In the cyclophosphamide group compared to control, a significant decrease was observed in mean total testis volume, seminiferous tubules volume (p<0.001), interstitial tissue volume (p<0.01), as well as in the length, diameter, and height of the germinal epithelium. basement membrane thickness, number of spermatogenic, Sertoli and Leydig cells, spermatogenesis indices, Johnsen score, and TAC level of testicular tissue (p<0.001), while the MDA level significantly increased (p<0.001). In the cyclophosphamide plus selenium group, these changes were compensated at the control level.
Conclusion: The results showed that cyclophosphamide induces oxidative stress, causes disruption in the structure and function of the testis. While selenium reduced these damages and improved important histological and oxidative stress parameters to levels similar to the control group, suggesting a protective role against cyclophosphamide-induced testicular damage.
Abstract Background Cyclophosphamide (CP), a commonly used chemotherapy drug, induces oxidative stress and damages testicular tissue, leading to impaired spermatogenesis. Objective This study aimed to evaluate the effects of selenium, a potent antioxidant, on sperm parameters in adult mice treated with CP. Materials and Methods In this experimental study, 32 adult male NMRI mice were randomly divided into 4 groups (n = 8/each): A) control, B) CP (100 mg/kg/wk, intraperitoneally), C) selenium (1 mg/kg/day, intraperitoneally), and D) CP + selenium. After 35 days of treatment, spermatozoa were collected from the caudal epididymis. Basic sperm parameters (motility, count, viability, morphology, and tail length), and functional parameters (plasma membrane integrity, nuclear maturity, and DNA damage) were evaluated. Daily sperm production was evaluated using the left testis. Serum levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) were also measured. Results In the CP group, sperm motility, count, viability, membrane integrity, normal morphology, tail length (p < 0.001), nuclear maturity (p < 0.05), DNA integrity, daily sperm production (p < 0.001), and TAC (p < 0.001) were significantly reduced, while MDA levels increased (p < 0.001) vs. controls. In the CP + selenium group, motility (p < 0.001), count (p < 0.01), viability (p < 0.001), membrane integrity, normal morphology (p < 0.01), tail length (p < 0.05), DNA integrity, daily sperm production (p < 0.001), and TAC (p < 0.05) significantly improved, with reduced MDA levels (p < 0.001) compared to CP group. Conclusion CP impaired sperm quality and antioxidant status through oxidative stress in mice, whereas selenium co-administration mitigated these adverse effects by improving sperm parameters, enhancing antioxidant capacity, and reducing lipid peroxidation, indicating protection against CP-induced reproductive toxicity.
Malek Soleimani Mehranjani, Sarina Garavand, Sepideh Ahmadi· International Journal of Rep...· 0 citations
BACKGROUND AND OBJECTIVE
Cyclophosphamide (CP) is a widely used chemotherapeutic agent whose clinical utility is limited by dose-dependent urotoxicity. This study investigated the sex-specific protective effects of hesperidin (HSP) against CP-induced bladder injury in rats, integrating biochemical, histological, and immunohistochemical outcomes.
METHODOLOGY
Adult male and female rats were allocated to control, HSP, CP, and HSP + CP groups (n = 8 per group). Oxidative stress and antioxidant status were assessed by malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Bladder architecture and fibrosis were evaluated using hematoxylin and eosin and Mallory's trichrome staining, while epithelial integrity and proliferative activity were examined by E-cadherin and Ki-67 immunoexpression, respectively. Data were analyzed using a two-way ANOVA to assess the effects of treatment and sex, as well as their interaction.
RESULTS
CP induced marked urotoxicity in both sexes, as evidenced by elevated MDA levels, depletion of GSH, CAT, and SOD, urothelial denudation, inflammation, collagen deposition, reduced E-cadherin expression, and increased Ki-67 immunoexpression. Female rats were more susceptible to CP-induced bladder injury, exhibiting greater mucosal damage, fibrosis, proliferative activity, collagen accumulation, higher MDA levels, and stronger Ki-67 expression than males. Hesperidin co-administration markedly attenuated CP-induced oxidative stress in both sexes. In male rats, hesperidin decreased MDA levels by 35.8% while increasing GSH, CAT, and SOD activities by 129.3%, 105.2%, and 18.5%, respectively, compared with the CP group. In female rats, the antioxidant effects were more pronounced, with MDA levels reduced by 73.9% and GSH, CAT, and SOD activities increased by 466.9%, 956.0%, and 203.2%, respectively, relative to the CP group. It also improved histoarchitectural alterations, reduced collagen accumulation, restored E-cadherin expression, and normalized Ki-67 levels toward control values, with a more pronounced protective effect in females. Hesperidin alone did not alter oxidative or structural parameters relative to controls.
CONCLUSION
Hesperidin co-administration substantially attenuated CP-induced bladder injury-reducing oxidative stress, improving histological architecture, limiting fibrosis, and restoring epithelial integrity and proliferative balance-with a more pronounced response in females; however, these benefits were partial, as most parameters did not fully return to control levels.
M. Abdelfattah, Sahar K. Ali, Rania Naguib et al.· Tissue & Cell· 0 citations
Background:
Cisplatin (CP) is an effective anticancer agent whose clinical use is limited by organ toxicity, including gonadotoxicity and accompanying male infertility. Letrozole (LTZ) is a nonsteroidal aromatase inhibitor that may improve spermatogenesis by stimulating endogenous testosterone synthesis.
Aim:
This study assessed the protective effect of LTZ against CP-induced testicular toxicity in a rat model.
Methods:
Twenty adult male Sprague-Dawley rats were randomly assigned to four groups (n = 5): NC, CP (7 mg/kg, single intraperitoneal dose), LTZ (1.5 mg/kg orally for 10 days), and CP + LTZ. The experimental period lasted for 28 days. Body weight, sperm count, sperm motility, sperm morphology, and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were assessed, and testicular tissues were histologically examined.
Results:
CP administration markedly reduced body weight gain, sperm count, and sperm motility and increased sperm morphological abnormalities. Serum levels of FSH, LH, and testosterone were also reduced in CP-treated rats. Histopathological examination revealed seminiferous tubular degeneration, germ cell necrosis, and interstitial damage. Coadministration of LTZ with CP improved sperm count, motility, and reproductive hormone concentrations and mitigated histopathological alterations. However, the morphological sperm abnormalities remained largely unchanged.
Conclusion:
CP causes critical structural and functional testicular damage. However, LTZ partially reduces CP-induced reproductive damage by restoring hormonal balance and improving spermatogenic activity. LTZ confers a promising adjunctive therapy to mitigate chemotherapy-induced infertility in males.
Mardin O. Mohammed, H. Dyary· Open Veterinary Journal· 0 citations
Soybean oil (SO) is used worldwide, whereas mustard oil (MO) consumption is generally limited to South Asia. Nevertheless, the organ-damaging effects of these substances at multiple doses over time have not been well studied. This study evaluated the hematobiochemical and histopathological effects of SO and MO in a mouse model. A total of 84 male Swiss albino mice, aged 5 weeks, were divided into seven groups (n=12 each): a control group (C) given pellets, and six treatment groups (S1-S3 and M1-M3) administered escalating doses of SO or MO at 15, 25, and 35 ml/kg for 60 days. Following euthanasia, blood samples were examined for hematological and biochemical parameters using standard assays. The hearts, livers, and kidneys were collected for measurement and then prepared for histopathology using H & E staining. The hematobiochemical parameters were significantly elevated in all treated groups when compared to the control group (P<0.05). The most significant changes were observed in the M3 group, except for HDL, which showed more pronounced differences in S1. Organ weights were also significantly increased in the treated groups. Histopathological examination revealed dose-dependent toxicity, with inflammatory cell infiltration in the S3 group and fat accumulation in the M2 and M3 hearts. Degenerative and apoptotic hepatocytes with vacuolation were observed in the livers, whereas congested arteries were observed in the kidneys. These findings highlight the risks of excess SO and MO intake related to obesity and organ toxicity, suggesting moderation in their use in diets.
Manal Sharif, M. Mahmud, Md. Islam et al.· Journal of Advanced Biotechn...· 0 citations
Chronic aluminum exposure was associated with an increase in Zip1 gene expression in the liver, whereas continuous administration of the oxidized pectin-oxymethyluracil complex normalized its expression to control levels, contributing to a reduction in AST and LDH activity.
T. G. Yakupova, A. Gizatullina, D. Karimov et al.· Experimental and Clinical Ga...· 0 citations
Biochemical and Histopathological Investigation of the Effect of Thymoquinone on Methotrexate-Induced Kidney Injury in Rats. Introduction and Aim: Methotrexate is one of the most widely used antimetabolite chemotherapeutics because it inhibits cell division. High doses of methotrexate are known to cause acute kidney injury. Antioxidant, anti-inflammatory and reducing effects of drug side effects of thymoquinone have been reported. The aim of this study is to biochemically and histopathologically investigate the effect of thymoquinone, a powerful antioxidant, in the acute kidney injury model induced by methotrexate in rats. Materials and Methods: In our study, male Wistar albino rats were used. The rats were divided into 4 groups, 6 in each group. Groups; I.Control, II. MTX, III. MTX + TQ (20 mg/kg) and IV. It is MTX + TQ (50 mg/kg). A single dose of corn oil was given to rats in the control group by gavage at 20 mg/kg for 5 days. A single dose of 20 mg/kg i.p. as MTX was given to secont, third and fourth group on the secont day of the experiment. 20 mg/kg TQ was given to the third group and 50 mg/kg TQ was given to the fourth group by gavage for five days. All animals were sacrificed at the end of the 6th day, and kidney tissue and blood samples were examined biochemically and histopathologically. Results: As a result of the biochemical analyses, it was observed that there was a significant increase in the urea, creatinine, KIM-1 and MIOX values in the KIM-1, MIOX and serum samples of the kindey tissue of the MTX group compared to the control group, and this increase decreased due to the use of TQ. While kidney tissue and serum GSH values decreased significantly in the MTX group compared to the control group, it was observed that the use of TQ increased the GSH value. Histopathological examinations revealed findings that may indicate oxidative damage in the kidney tissues of the MTX group. When the MTX and control groups were compared while these findings were significant (p<0.05) in both groups, it was observed that these histopathological changes significantly reduced in the groups receiving TQ. Conclusion: It was determined that the use of thymoquinone against kidney damage caused by methotrexate in rats prevented this damage with its antioxidant and other properties. Accordingly, clinically advanced studies are needed for the use of thymoquinone with chemotropic drugs. Keywords: Acute Kidney Injury, KIM-1, MIOX, Methotrexate, Thymoquinone.
