Doxorubicin-mediated testicular toxicity is associated with dysregulated mTOR/Beclin-1 pathways, oxidative stress, inflammation and apoptosis in Wistar rats: preventive role of lutein

Figures

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  Fig. 1. Lutein prevents DOX-induced dysregulation of hormones and steroidogenesis. (A) Follicle stimulating hormone (FSH) (B) Luteinizing hormone (LH) (C) Testosterone. Data expressed as mean ± SEM, n = 5. Analysis by one-way ANOVA followed by Tukey post-hoc test. * p < 0.05, versus Control. # p < 0.05, versus DOX

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  Fig. 2. Lutein prevents DOX-induced steroidogenesis dysregulation. (A) 17α-hydroxylase (B) 3β-Hydroxyl steroid dehydrogenase (3β-HSD). Data expressed as mean ± SEM of n = 5. Analysis by one-way ANOVA followed by Tukey post-hoc test. * p < 0.05, versus Control. # p < 0.05, versus DOX. LUT = Lutein while DOX = Doxorubicin

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  Fig. 3. Lutein protects against DOX-induces sperm abnormalities (A) motile cell (B) non-motile cell, (C) Sperm count. (D) Normal morphology (E) Semen volume. Data expressed as mean ± SEM of n = 5. Analysis by one-way ANOVA followed by Tukey post-hoc test. * p < 0.05, versus Control. # p < 0.05, versus DOX. LUT = Lutein while DOX = Doxorubicin

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  Fig. 4. Lutein averted DOX-induced testicular oxidative stress. (A) Glutathione (GSH) (B) Glutathione s-transferase (GST) (C) Catalase (D) Superoxide dismutase (SOD) (E) Malondialdehyde (MDA) (F) Nitrite. Data expressed as mean ± SEM of n = 5. Analysis by one-way ANOVA followed by Tukey post-hoc test. * p < 0.05, versus Control. # p < 0.05, versus DOX. LUT = Lutein while DOX = Doxorubicin

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  Fig. 5. Lutein modulates DOX-induced inflammatory cytokines. (A) Tumor necrosis factor-alpha (TNF-α) (B) Interleukin 6 (IL-6). Data expressed as mean ± SEM of n = 5. Analysis by one-way ANOVA followed by Tukey post-hoc test. * p < 0.05, versus Control. # p < 0.05, versus DOX. LUT = Lutein while DOX = Doxorubicin

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  Fig. 6. Lutein downregulates DOX-induced apoptotic process. (A) caspase-3 (B) B-cell lymphoma factor 2 (Bcl-2). Data expressed as mean ± SEM of n = 5. Analysis by one-way ANOVA followed by Tukey post-hoc test. * p < 0.05, versus Control. # p < 0.05, versus DOX. LUT = Lutein while DOX = Doxorubicin

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  Fig. 7. Lutein prevent DOX-induced dysregulation of testicular autophagy signaling (A) mammalian target of rapamycin (mTOR) (B) Beclin-1. Data expressed as mean ± SEM of n = 5. Analysis by one-way ANOVA followed by Tukey post-hoc test. * p < 0.05, versus Control. # p < 0.05, versus DOX. LUT = Lutein while DOX = Doxorubicin

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  Fig. 8. Lutein prevented abnormal testicular histopathology. (A) Control (B) DOX (C) LUT (D) LUT + DOX. Red arrows indicate areas of significant lesion. The slide was stained with H&E and photographed with microscope at X400 magnification. LUT = Lutein while DOX = Doxorubicin

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  Fig. 9. Lutein abates testicular fibrosis A) Control (B) DOX (C) LUT (D) LUT + DOX. Tissues were stained with mason trichrome and snapped at X400 magnification. Data expressed as mean ± SEM of n = 5. Analysis by one-way ANOVA followed by Tukey post-hoc test. * p < 0.05, versus Control. # p < 0.05, versus DOX. LUT = Lutein while DOX = Doxorubicin

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  Fig. 10. Graphical illustration of preventive mechanism of action of lutein