• Evaluation of protective effect of resveratrol loaded solid lipid nanoparticles on reducing radiation-induced or doxorubicin injection damages on mice spermatogenesis system.
  • Mohammad Farhadi Rad,1 Masoud najafi,2,* faranak aghaz,3 Elham Arkan,4 Kamran mansouri,5
    1. Department of Radiology and nuclear medicine, School of paramedical, Kermanshah University of Medical Sciences, Kermanshah, Iran
    2. Department of Radiology and nuclear medicine, School of paramedical, Kermanshah University of Medical Sciences, Kermanshah, Iran
    3. Nano Drug Delivery Research Center, Faculty of Pharmacy, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
    4. Nano Drug Delivery Research Center, Faculty of Pharmacy, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
    5. Medical Biology Research Center,Kermanhah University of Medical sciences,Kermanhah.Iran


  • Introduction: Resveratrol (RES), a naturally occurring polyphenol known as 3,4’,5-trihydroxystilbene. Remarkably, RES has been identified in over 70 plant species. Extensive research has uncovered a multitude of therapeutic benefits associated with RES, encompassing antioxidant, anti-hyperlipidemic, immuno-modulatory, anti-platelet, anti-inflammatory, anti-carcinogenic, neuroprotective, vasorelaxant, and cardioprotective effects.. Radiotherapy and chemotherapy are widely employed therapeutic approaches for cancer management. While these treatments have demonstrated favorable outcomes in cancer control, it is crucial to recognize that they can impart deleterious effects on non-cancerous cells, thereby instigating a cascade of undesired events such as heightened oxidative stress within cellular systems. Undoubtedly, the manifestation of these side effects can considerably impact the quality of life for patients. Consequently, the imperative pursuit of discovering and developing novel, efficacious compounds that can mitigate these adverse effects and protect normal tissues should be given utmost priority. New ways have been opened to increase the efficacy of the therapeutic effects of the molecules by nano drug delivery system, Especially Solid lipid nanoparticles (SLN) have reported to be as promising nanocarriers in cancer therapy SLN have reported to be as promising nanocarriers in cancer therapy. The purpose of this study was to evaluate protective effects of resveratrol as an antioxidant agent loaded by Solid lipid nano particles against toxicity of induced radiation and doxorubicin (as a chemotherapy drug) in testis tissue. In recent years, novel approaches have emerged to enhance the therapeutic efficacy of molecules through nano drug delivery. Solid lipid nanoparticles (SLN) have gained significant attention as potential nanocarriers for cancer treatment. The objective of this research was to assess the protective properties of resveratrol, an antioxidant agent encapsulated within Solid lipid nanoparticles, against the detrimental effects of radiation-induced toxicity and doxorubicin, a chemotherapy drug, on testicular tissue.
  • Methods: Solid lipid nanoparticles (SLNs) were generated through the utilization of high shear homogenization. The physicochemical characteristics of the SLNs were assessed employing Dynamic Light Scattering (DLS), which provided measurements for the average particle size and Zeta-potential to gauge the stability of the nanoparticles in suspension. Additionally, scanning electron microscopy (SEM) was utilized to evaluate morphological properties. The release of the drug was investigated by means of a dialysis bag with a molecular weight cutoff of 20 kD. To examine the cytocompatibility of SLN, RES, and RES-SLN, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed. Furthermore, the chemical interactions among different functional groups were assessed using FT-IR spectroscopy through the employment of the potassium bromide disk method. In this experiment, a total of 60 adult male mice, aged 4-5 weeks and weighing between 25-35g, were utilized. The mice were classified into six different groups, and their oxidative stress parameters were evaluated. The first group, referred to as the control group treated with normal salin 0.9%. The second group was administered a dosage of 3 mg/kg of DOX every other day for a duration of three days. The third group was exposed to a radiation dose of 2 gray (Gy) at a rate of 300 cGy per minute. The fourth group received a daily dosage of 10 mg/kg of SLN-RES for a duration of seven days. The fifth group underwent a combined treatment involving a dosage of 3 mg/kg of DOX every other day for three days then 10 mg/kg of SLN-RES per day for seven days. Lastly, the sixth group was subjected to a daily dosage of 10 mg/kg of SLN-RES for seven days, befor a radiation dose of 2 Gy. Subsequently, the assessment of the induced damage caused by radiation and DOX, as well as the protective effects of RES-SLN, was carried out by evaluating the levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the testis tissue.
  • Results: The findings suggest that RES-SLNs exhibit an average size of 246nm, demonstrating favorable stability characterized by a zetapotential of -15mV. Moreover, SEM imaging confirms the spherical nature of the nanoparticles. Notably, the encapsulation efficiency (EE) and drug loading (DL) rates were determined to be 72% and 12%, respectively. Furthermore, the cytocompatibility of RES-SLN with fibroblast cells was validated through the MTT assay, affirming its safety for in vivo biomedical applications. The findings of this study highlight that the irradiation and administration of doxorubicin led to a substantial elevation in the level of MDA within the testes of mice. Nevertheless, the injection of RES-SLN displayed a restorative effect, effectively bringing the MDA levels back to baseline. Furthermore, the activity of SOD exhibited a notable decline in the irradiated and doxorubicin-treated group. However, following the injection of RES-SLN, the SOD activity returned to the levels observed in the normal group.
  • Conclusion: In conclusion, the utilization of RES-SLN demonstrates its capacity to shield the testes of mice from the detrimental consequences of irradiation and doxorubicin while showcasing significant promise within the realm of clinical application.
  • Keywords: Radiation, Doxorubicin, Resveratrol, Solid lipid nanoparticle, Spermatogenesi, MDA, SOD