The Optimal Effective Dose of Adipose-Derived Stem Cell Exosomes in Wound Healing.

INTRODUCTION: Although the effect of adipose-derived mesenchymal stem cell exosomes (ADSC-exos) on wound healing with different doses are shown in various studies, efficient and sufficient doses of ADSC-exos are still unknown. The study aimed to determine the optimal dose of ADSC-exos in wound healing. METHODS: The 45 Sprague-Dawley rats were randomly divided into five groups, with seven animals in each. After dorsal circular defects were created, each wound was injected as follows: group 1: saline, group 2: 10 µg/mL of ADSC-exos, group 3: 100 µg/mL of ADSC-exos, group 4: 200 µg/mL of ADSC-exos, and group 5: 400 µg/mL of ADSC-exos. The effects of ADSC-exos on epithelization, angiogenesis, and collagen formation were analyzed macroscopically, histopathologically, and immunohistochemically on day 14. RESULTS: A total of 200 µg/mL and 400 µg/mL ADSC-exos groups had higher epithelial tongue length, epithelial tongue area, and angiogenesis scores than the other groups. Although there was no statistical difference in fibrosis scores among groups, collagen fibers were becoming well-organized as the ADSC-exos doses increased. While the wound area was clinically smaller in the 200 µg/mL ADSC-exos group, there was no statistically significant difference among groups on day 14. CONCLUSIONS: A total of 200 µg/mL of ADSC-exos was found to be the adequate and effective dose for re-epithelialization and angiogenesis in cutaneous wound healing. Moreover, the collagen density increased with a more regular pattern in the 200 µg/mL group, which can be important in scar regulation.

Alantolactone ameliorates graft versus host disease in mice.

The anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD. The study included 4 BALB/c groups as hosts: Naïve (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100 mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2-18 (n = 4) and non-GVHD patients between ages 2-50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used for ELISA. ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores. CD8+ T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a more naïve phenotype (CD62L+ CD44-). ALT did not alter Treg cell number or frequency. ALT treatment appears to suppress myeloid cell lineage (CD11c+). Consistent with reduced myeloid lineage, liver and small intestine levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in pro-inflammatory cytokines but there was no statistical significance. Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD model.

The efficacy of mesenchymal stem cell treatment and colistin-fosfomycin combination on colistin-resistant Acinetobacter baumannii sepsis model.

INTRODUCTION: This study examines the role of mesenchymal stem cells (MSCs) in an experimental sepsis model developed with colistin-resistant Acinetobacter baumannii (CRAB). MATERIALS AND METHODS: BALB-c mice were divided into treatment groups (MSC, MSC + colistin (C)-fosfomycin (F), and C-F and control groups (positive and negative)). CRAB was administered to mice through intraperitoneal injection. Three hours later, C, F, and MSC were given intraperitoneally to the treatment groups. Colistin administration was repeated every 12 h, F administration was done every 4 h, and the second dose of MSC was administered after 48 h. Mice were sacrificed at 24 and 72 h. The bacterial load was determined as colony-forming units per gram (cfu/g). Histopathological examination was conducted on the left lung, liver, and both kidneys. IL-6 and C-reactive protein (CRP) levels in mouse sera were determined by enzyme-linked immunosorbent assay. RESULTS: Among the treatment groups, the C-F group had the lowest colony count in the lung (1.24 ± 1.66 cfu/g) and liver (1.03 ± 1.08 cfu/g). The highest bacterial clearance was observed at 72 h compared to 24 h in the MSC-treated groups (p = 0.008). The MSC + C-F group showed the lowest histopathological score in the liver and kidney (p = 0.009). In the negative control group, the IL-6 level at the 24th hour was the lowest (p < 0.001). Among the treatment groups, the CRP level was the lowest in the MSC + C-F group at 24 and 72 h. CONCLUSION: In a CRAB sepsis model, adding MSCs to a colistin-fosfomycin treatment may be beneficial in terms of reducing bacterial loads and preventing histopathological damage.

The effect of oral hydroxychloroquine on chondral defect: An experimental study.

OBJECTIVES: This study aims to evaluate the time- and dose-dependent effects of oral hydroxychloroquine (HCQ) on focal full-thickness knee chondral defect healing in a rabbit model. MATERIALS AND METHODS: Cartilage defects of 4x4 mm2 were created on both medial femoral condyles of 24 New Zealand rabbits. The rabbits were divided into six groups (A-F) according to HCQ administration and sacrifice time: A (three-week control) and B (six-week control) received no additional interventions; C (20 mg/kg HCQ, three weeks); D (20 mg/kg HCQ, six weeks); E (40 mg/kg HCQ, three weeks); and F (40 mg/kg HCQ, six weeks). Osteochondral specimens were evaluated macroscopically, histologically, and immunohistochemically. The terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method was used to detect apoptotic cells. RESULTS: The International Cartilage Repair Society (ICRS) scores were significantly higher in the experimental groups than in the controls (p<0.001). The Wakitani scores in Group D showed a significant improvement compared to those in Group B (p<0.01). The 20 mg/kg HCQ treatment groups showed better recovery than the controls (p<0.01). High-dose HCQ (40 mg/kg) treatment significantly reduced the intensity of collagen type 2 immunoreactivity compared to that in the groups receiving 20 mg/kg of HCQ (p<0.01). Collagen type 2 expression in Group F was significantly lower than that in Group D (p<0.01). There were more TUNEL-positive cells in the repair sites of Groups E and F than in the lower-dose experimental groups and untreated experimental groups (p<0.001). CONCLUSION: A low dose of HCQ improved cartilage repair, while higher doses of HCQ exerted a negative effect on cartilage regeneration in rabbits. In the presence of defective cartilage, the use of HCQ at an appropriate dose and time is important for cartilage health.

Investigation of the anti-oxidative and anti-inflammatory effects of melatonin on experimental liver damage by radiation.

Radiotherapy is one of the inevitable treatment approaches for several types of cancer. We aimed to show the protective and therapeutic effects of daily use of melatonin on liver tissues subjected to a single dose of 10 Gy (gamma-ray) total body radiation. Rats were divided into 6 groups, of which 10 were in each: control, sham, melatonin, radiation, radiation+melatonin, and melatonin+radiation. The rats received 10 Gy of external radiation throughout their entire bodies. The rats were given 10 mg/kg/day of melatonin intraperitoneally before or after radiation treatment, depending on the group. Histological methods, immunohistochemical analysis (Caspase-3, Sirtuin-1, α-SMA, NFΚB-p65), biochemical analysis by ELISA (SOD, CAT, GSH-PX, MDA, TNF-α, TGF-ß, PDGF, PGC-1α) and the Comet assay as a marker of DNA damage were applied to the liver tissues. Histopathological examinations showed structural changes in the liver tissue of the radiation group. Radiation treatment increased the immunoreactivity of Caspase-3, Sirtuin-1 and α-SMA, but these effects were relatively attenuated in the melatonin-treated groups. The melatonin+radiation group had statistically significant results close to those of the control group, in terms of Caspase-3, NFΚB-p65 and Sirtuin-1 immunoreactivity. In melatonin treated groups, hepatic biochemical markers, MDA, SOD, TNF-α, TGF-ß levels, and DNA damage parameters were decreased. Administration of melatonin before and after radiation has beneficial effects, but using it before radiation may be more efficient. Accordingly, daily melatonin usage could mitigate ionizing radiation induced damage.

The neuroprotective effect of mesenchymal stem cells in colistin-induced neurotoxicity.

Colistin is an effective antibiotic against multidrug-resistant gram-negative bacterial infections; however, neurotoxic effects are fundamental dose-limiting factors for this treatment. Stem cell therapy is a promising method for treating neuronal diseases. Multipotent mesenchymal stromal cells (MSC) represent a promising source for regenerative medicine. Identification of neuroprotective agents that can be co-administered with colistin has the potential to allow the clinical application of this essential drug. This study was conducted to assess the potential protective effects of MSC, against colistin-induced neurotoxicity, and the possible mechanisms underlying any effect. Forty adult female albino rats were randomly classified into four equal groups; the control group, the MSC-treated group (A single dose of 1 × 106/mL MSCs through the tail vein), the colistin-treated group (36 mg/kg/d colistin was given for 7 d) and the colistin and MSC treated group (36 mg/kg/d colistin was administered for 7 d, and 1 × 106/mL MSCs). Colistin administration significantly increased GFAP, NGF, Beclin-1, IL-6, and TNF-α immunreactivity intensity. MSC administration in colistin-treated rats partially restored each of these markers. Histopathological changes in brain tissues were also alleviated by MSC co-treatment. Our study reveals a critical role of inflammation, autophagy, and apoptosis in colistin-induced neurotoxicity and showed that they were markedly ameliorated by MSC co-administration. Therefore, MSC could represent a promising agent for prevention of colistin-induced neurotoxicity.

EVs vs. EVs: MSCs and Tregs as a source of invisible possibilities.

Extracellular vesicles (EVs) are produced by various cells and exist in most biological fluids. They play an important role in cell-cell signaling, immune response, and tumor metastasis, and also have theranostic potential. They deliver many functional biomolecules, including DNA, microRNAs (miRNA), messenger RNA (mRNA), long non-coding RNA (lncRNA), lipids, and proteins, thus affecting different physiological processes in target cells. Decreased immunogenicity compared to liposomes or viral vectors and the ability to cross through physiological barriers such as the blood-brain barrier make them an attractive and innovative option as diagnostic biomarkers and therapeutic carriers. Here, we highlighted two types of cells that can produce functional EVs, namely, mesenchymal stem/stromal cells (MSCs) and regulatory T cells (Tregs), discussing MSC/Treg-derived EV-based therapies for some specific diseases including acute respiratory distress syndrome (ARDS), autoimmune diseases, and cancer.

Changes in the histopathology and in the proteins related to the MAPK pathway in the brains of rats exposed to pre and postnatal radiofrequency radiation over four generations.

The development of new technologies and industry increases the number and variety of electromagnetic field (EMF) sources. Researcher are increasingly interested in the effects of EMF on brain health. The brain's function is largely dependent on electrical excitability, so it would be expected to be vulnerable to EMF. We therefore investigated the effects of brain development in the fetus, histopathological changes in female rats and the hippocampal level of MAPK proteins in male rats after exposed to pre and postnatal 2450 MHz continuous wave (CW) radiofrequency radiation (RFR) over four generations. Four groups; sham, irradiated female, irradiated male, irradiated male and female, with each consisting of four rats (one male and three females) were created. Rats in the exposure groups were whole-body exposed to 2450 MHz CW-RFR for 12 h/day during the experiment. Irradiation started one month before fertilization in the experimental group. On the 18th day of the gestational period, one pregnant rat from each group was decapitated under general anesthesia and the fetuses were taken. The remaining two pregnant rats completed the normal gestation period. When the offspring were two months old, four rats, one male and three female, were allocated for the second generation study. Next generation animals were also experienced the same processes as the first generation rats. This study were evaluated development of brain in fetuses and histopathological changes in brain of female rats using haematoxylin eosin staining, and the hippocampal level of MAPK proteins in brain of male rats by Western Bloting. We observed hemorrhagic areas, irregular cellular localization and vascular structures in the brain of fetal and adult female rat of exposed groups in the all generations. pERK, ptau, pJNK and pP38 were increased in the brain of adult male rat of exposed groups in the all generations (p < 0.005). Pre and postnatal 2450 MHz continuous wave radiofrequency radiation exposure may cause changes in the function of the MAPK pathway affecting cognitive processes such as learning and memory and may cause damage to both the fetus and adult brain tissue. Also, EMF may have potential to affect brain of future generations.

Protective effect of pycnogenol against gamma radiation-induced lung injury in rat: DNA damage, lipid peroxidation, antioxidant levels, and histopathological changes.

Background and Objective: The study aims to evaluate the histopathological changes, enzymatic alterations, and DNA damage in rat lungs induced by whole-body gamma irradiation as well as evaluation of the protective effect of pycnogenol. Materials and Methods: A hundred adult male rats were equally divided into ten groups including control, four antioxidants, γ-irradiation, four antioxidant + γ-irradiations. This study began the day before radiation treatment and continued for 3 days. The pycnogenol was dissolved 5% dimethyl sulfoxide and then administered orally through a gastric tube at a dose of 37.5 mg/kg, 75 mg/kg, 150 mg/kg, and 300 mg/kg in 24, 48, and 72 h before irradiation. Irradiation was applied with a whole-body irradiation dose of 900 cGy in one fraction. DNA damage, histopathological changes, catalase (CAT), and superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in lung tissue of rats were evaluated 3 days after irradiation. Results: CAT and SOD activities were found to be significantly lower in the irradiation group than control (P < 0.001). CAT and SOD activities were higher in the antioxidant + γ-irradiation group than both irradiation and control groups. MDA levels were significantly higher in the irradiation group compared to control (P < 0.001), whereas MDA levels decreased in the antioxidant + γ-irradiation group compared to the irradiation group. The antioxidant groups were significantly increased comet parameters depend on pycnogenol doses compared to control. The antioxidant + γ-irradiation was decreased comet parameter compared to γ-irradiation. As a result of the histopathologically, the antioxidant groups were different than the control group that in the areas of alveolar sacs and connective tissue areas were seen hemorrhage areas similar to the irradiation group. Conclusion: We demonstrate that 300 mg/kg of pycnogenol might provide significant protection against deleterious effects from whole-body ionizing radiation on the lung tissue. P300+ γ-ray group was significantly reduced radiation-induced lung injury and was possible to observe significantly preservation.

Efficacy of stem cell-based therapies for colistin-induced nephrotoxicity.

The increase in infections with multidrug resistant bacteria has forced to return to the use of colistin, antibiotic with known nephrotoxicity. Mesenchymal stem cells (MSCs) are being extensively investigated for their potential in regenerative medicine. This study aimed to investigate the possible protective mechanisms of the MSCs against kidney injury induced by colistin. Forty adult female albino rats were randomly classified into 4 equal groups; the control group, the MSC-treated group (a single dose of 1 ×106 /ml MSCs through the tail vein), the colistin-treated group (36 mg/kg/day colistin was given for 7 days), and the both colistin and MSC group (36 mg/kg/day colistin and 1 ×106 /ml MSCs). Main outcome measures were histopathological alterations, kidney malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and immunohistological autophagy evaluation. MSC repressed the progression of colistin-induced kidney injury as evidenced by the improvement of histopathological alterations and the substantial increase MDA, and decrease SOD and CAT in serum levels. Moreover, MSC resulted in a profound reduction in oxidative stress as manifested by decreased MDA and increased SOD in serum. Notably, MSC suppressed colistin-induced autophagy; it reduced renal levels of Beclin-1, P62 and LC3A/B. Furthermore, MSC decreased renal levels of eNOS. Lastly, MSC efficiently decreased expression of the TUNEL positive cell number. MSC confers protection against colistin-induced kidney injury by alleviating oxidative stress, nitric oxide synthase besides modulating reducing autophagy and apoptosis.

Effects of pre and postnatal 2450 MHz continuous wave (CW) radiofrequency radiation on thymus: Four generation exposure.

This study aims to investigate the effects of pre- and postnatal 2450 MHz continuous wave (CW) radiofrequency radiation (RFR) on the thymus of rats spanning four generations. Four groups; sham, irradiated female, irradiated male, irradiated male and female, each consisting of four rats (one male and three females), were created. During the experiment, rats in the exposure groups were whole-body exposed to 2450 MHz CW-RFR for 12 h/day. Irradiation started one month before the fertilization in the experimental group. When the offspring were two months old, four rats, one male and three female, were allocated for the second-generation study. The remaining offspring were sacrificed under general anesthesia, and their thymuses were removed. The same procedure was applied to the next generation. Two months after the second generation gave birth, third-generation rats were decapitated, and their thymuses were removed. In all groups, cortex, medulla and resident cells could be clearly distinguished in the second and third generations. No differences were observed between the control and two experimental groups, defined as irradiated female and irradiated male. In contrast, vascularization was observed in the thymus of the fourth-generation offspring of the group where both males and females were irradiated. The number of offspring and mass of all rats decreased in the third-generation group. Pre-and postnatal 2450 MHz continuous wave radiofrequency radiation exposure may potentially affect the thymus of future generations.

Therapeutic effects of vitamin D and IL-22 on methotrexate-induced mucositis in mice.

Mucositis is a common side effect of cancer therapies and transplant conditioning regimens. Management of mucositis involves multiple approaches from oral hygiene, anti-inflammatory, anti-apoptotic, cytoprotective, and antioxidant agents, to cryo-therapy, physical therapy, and growth factors. There is room for novel, affordable treatment options, or improvement of currently available therapies. Vitamin D has been shown to regulate mucosa-resident cell populations such as Th17 or innate lymphoid cells and critical mucosal cytokine IL-22; however, their therapeutic potential has not been put to test in preclinical mouse models. In this study, we aimed to test the therapeutic potential of vitamin D injections and IL-22 overexpression in a murine model of chemotherapy-induced mucositis. Balb/c mice were given daily intraperitoneal injections of vitamin D. Mucositis was induced by methotrexate. Another group received IL-22 plasmid via hydrodynamic gene delivery. Weight loss and intestinal histopathology, intestinal levels of cytokines IL-22, IL-17A, GM-CSF, IL-23, IFN-γ, TNF-α, and IL-10, and number of intestinal lamina propria B cell, neutrophil, and total innate lymphoid cells were quantified. Daily vitamin D injections ameliorated intestinal inflammation and elevated intestinal IL-22 levels compared with control groups. Temporal overexpression of IL-22 by hydrodynamic gene delivery slightly increased intestinal IL-22 but failed to confer significant protection from mucositis. To our knowledge, this is the first experimental demonstration in an animal model of mucositis of therapeutic use of vitamin D and IL-22 supplementation and our results with vitamin D suggest it may have merit in further trials in human mucositis patients.

A novel hemostatic scaffold material and the importance of scaffold formation on ending hemorrhage: An experimental rat study.

BACKGROUND: Different pharmacological agents are developed to control bleeding. However, it is critical for these agents to induce thrombin formation and have an effect on vasoconstriction, coagulation, and scaffold. In this study, we aimed to demonstrate the agents' ability to stop bleeding properties on minor and major open bleedings after skin clefts, extracorporal injuries, traumatic cuts, spontaneous or surgical intervention besides scaffold properties. For this purpose, a new and authentic hemostatic agent, processed diatomite (PD) and the most preferred chitosan in the medical area were used to test blood stopping and scaffold effects in a rat femoral bleeding model. The samples were examined by scanning electron microscopy (SEM), and the results on blood stopping were shared. METHODS: The current experimental study was conducted on rats. The effects of hemostatic agents on our femoral bleeding model were determined. In this study, 22 male Wistar albino rats weighing 158-215 g, were used. The rats were assigned randomly to three groups: control group (n=6), chitosan group (n=8), and PD group (n=8). Bleeding time, scaffold formation, weight differences, histopathological effect and scanning electron microscope (SEM) analyses were performed. RESULTS: In our experimental model, weight loss was 5.0±1.3 g for the control group, 2.9±1.1 g for the chitosan group, and 2.7±1.0 g for the PD group, respectively. When weighed before and after the experiment, there was a significant change in weights of rats in chitosan, and PD groups regarding scaffold formation: it was complete for six rats (75%) and weak for two (25%) rats in chitosan group; however, it was complete for seven rats (87.5%) and weak for one (12.5%) rat in the PD group. Scaffold formation was significant for the chitosan and PD groups versus the control group (p=0.002). CONCLUSION: In our study, the scaffold formed by PD exerts appropriate porousness and contributes to fibrin formation and prevent re-bleeding. PD had a strong and significant scaffold effect. The effectiveness of PD to stop bleeding was equal to chitosan. Besides being natural, hemostatic agents should not induce cellular damage. We histopathologically demonstrated that PD was harmless for the natural structure of cells and vessels in the femoral site.

The effect of N-acetylcysteine on inflammation and oxidative stress in cisplatin-induced nephrotoxicity: a rat model

Background/Aim: Cisplatin is a highly effective chemotherapeutic agent used in the treatment of solid organ cancers. Besides its chemotherapeutic effectiveness, cisplatin administration is associated with numerous side effects. Of those, the most clinically significant and common effect is nephrotoxicity. Recent studies reported that oxidative stress and inflammation are probably the most important mechanisms that contribute to the nephrotoxicity. N-acetylcysteine (NAC) is an antioxidant and antiinflammatory agent. In the present study, the effects of NAC on cisplatin-induced nephrotoxicity were investigated. Materials and methods: Rats were divided into four groups each including eight rats: CONT, NAC-250, CP, and CP+NAC. Rats in experimental groups were treated intraperitoneally (i.p.) with a single dose of cisplatin (10 mg/kg body weight) and i.p. with NAC (250 mg/kg body weight) for three consecutive days. Nephrotoxicity was determined by plasma BUN and creatinine levels. In tissue samples, myeloperoxidase (MPO), nuclear factor-kappa B (NF-kB), high mobility group box-1 (HMGB-1), total oxidant status (TOS), and total antioxidant status (TAS) levels were measured. Kidneys were analyzed histopathologically as well. Results: It was revealed that cisplatin was not effective on MPO, HMGB-1 and NF-kB levels but did increase TOS levels and decrease TAS levels in tissue samples. Interestingly, NAC elevated MPO and HMGB-1 levels significantly. Nevertheless, NAC ameliorated histological and functional changes in kidney tissues. Conclusion: It is suggested that inflammation has a limited effect on cisplatin nephrotoxicity in this experimental design, and, as reflected by decreased BUN and creatinine levels, NAC can be used as an additional therapeutic agent in standard cisplatin treatment protocols.

The effects of gilaburu (Viburnum opulus) juice on experimentally induced Ehrlich ascites tumor in mice.

OBJECTIVE: The aim of study was to investigate anticancer effect of Viburnum opulus (VO) on Ehrlich ascites carcinoma (EAC) bearing mice that treated with different concentrations of VO. MATERIALS AND METHODS: For tumor transplantation; mice were inoculated with 1 × 106 EAC cells intraperitoneally and than divided into five groups (n = 9). Two hours after inoculation; experimental groups were treated daily with VO extract at doses of 1000 mg/kg, 2000 mg/kg, 4000 mg/kg. RESULTS: Extracts obtained from gilaburu juice can have hinder effect on tumor cell growth. CONCLUSION: As far as we known, this is the first study about in vivo antitumoral activity of VOon Ehrlich ascites tumor model, and consequently VO extract exhibited anticancer activity against EAC-bearing mice.

Effects of Cinnamon (C. zeylanicum) Bark Oil Against Taxanes-Induced Damages in Sperm Quality, Testicular and Epididymal Oxidant/Antioxidant Balance, Testicular Apoptosis, and Sperm DNA Integrity.

The aim of this study was to investigate whether cinnamon bark oil (CBO) has protective effect on taxanes-induced adverse changes in sperm quality, testicular and epididymal oxidant/antioxidant balance, testicular apoptosis, and sperm DNA integrity. For this purpose, 88 adult male rats were equally divided into 8 groups: control, CBO, docetaxel (DTX), paclitaxel (PTX), DTX+PTX, DTX+CBO, PTX+CBO, and DTX+PTX+CBO. CBO was given by gavage daily for 10 weeks at the dose of 100 mg/kg. DTX and PTX were administered by intraperitoneal injection at the doses of 5 and 4 mg/kg/week, respectively, for 10 weeks. DTX+PTX and DTX+PTX+CBO groups were treated with DTX during first 5 weeks and PTX during next 5 weeks. DTX, PTX, and their mixed administrations caused significant decreases in absolute and relative weights of all reproductive organs, testosterone level, sperm motility, concentration, glutathione level, and catalase activity in testicular and epididymal tissues. They also significantly increased abnormal sperm rate, testicular and epididymal malondialdehyde level, apoptotic germ cell number, and sperm DNA fragmentation and significantly damaged the histological structure of testes. CBO consumption by DTX-, PTX-, and DTX+PTX-treated rats provided significant ameliorations in decreased relative weights of reproductive organs, decreased testosterone, decreased sperm quality, imbalanced oxidant/antioxidant system, increased apoptotic germ cell number, rate of sperm with fragmented DNA, and severity of testicular histopathological lesions induced by taxanes. In conclusion, taxanes cause impairments in sperm quality, testicular and epididymal oxidant/antioxidant balance, testicular histopathological structure, and sperm DNA integrity, and long-term CBO consumption protects male reproductive system of rats.