Cyclophosphamide-induced Oxidative Stress Research Articles

Melatonin prevents overproduction of reactive oxygen species and vascular dysfunction induced by cyclophosphamide

AimsOverproduction of reactive oxygen species (ROS) is a pathologic hallmark of cyclophosphamide toxicity. For this reason, antioxidant compounds emerge as promising tools for preventing tissue damage induced by cyclophosphamide. We hypothesized that melatonin would display cytoprotective action in the vasculature by preventing cyclophosphamide-induced oxidative stress. Materials and methodsMale C57BL/6 mice (22–25 g) were injected with a single dose of cyclophosphamide (300 mg/kg; i.p.). Mice were pretreated or not with melatonin (10 mg/kg/day, i.p.), given during 4 days before cyclophosphamide injection. Functional (vascular reactivity) and oxidative/inflammatory patterns were evaluated at 24 h in resistance arteries. The antioxidant action of melatonin was assessed in vitro in cultured vascular smooth muscle cells (VSMCs) of mesenteric arteries. Key findingsCyclophosphamide induced ROS generation in both mesenteric arterial bed (MAB) and cultured VSMCs, and this was normalized by melatonin. Cyclophosphamide-induced ROS generation and lipoperoxidation in the bladder and kidney was also prevented by melatonin. Increased levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were detected in the MAB of cyclophosphamide-treated mice, all of which were prevented by melatonin. Functional assays using second-order mesenteric arteries of cyclophosphamide-treated mice revealed a decrease in vascular contractility. Melatonin prevented vascular hypocontractility in the cyclophosphamide group. Melatonin partially prevented the decrease in myeloperoxidase (MPO) and N-acetyl-beta-D-glucosaminidase (NAG) activities in the MAB of the cyclophosphamide group. SignificanceMelatonin may constitute a novel and promising therapeutic approach for management of the toxic effects induced by cyclophosphamide in the vasculature.

Evaluation of The Effect of Fisetin against Cyclophosphamide-Induced Myelosuppression and Oxidative Stress in Male Albino Rats

Myelosuppression is a serious disease that is related to the malfunction of blood cells production that leads to cytopenia which is the most serious hematologic toxicity of cancer chemotherapies including cyclophosphamide, which is a strong oxazaphosphorine [a nitrogen mustard alkylating agent] that can be used alone or combined with other chemotherapeutic agents for the treatment of different malignant diseases. It induces severe bone marrow suppression by damaging hematopoietic stem cells through the generation of oxidative stress. Fisetin is a hydrophobic polyphenolic compound with a wide range of pharmacological properties such as antioxidant, anti-inflammatory, antimicrobial, osteoprotective, antidiabetic, and anti-carcinogenic activities. The present study aims to evaluate the effects of fisetin alone and pretreatment with cyclophosphamide on some selected hematological and oxidative stress parameters in the male rats model. Animals were randomly divided into 4 groups each with 7 rats. The first group received 1% dimethyl sulfoxide (negative control group). The second group received oral fisetin. The third group received a single intraperitoneal (IP) injection of cyclophosphamide (CP) and the fourth group received fisetin for 7 constitutive days than a single IP injection of CP on day 7. Results showed that both fisetin and CP significantly reduced the total white blood cells and platelet counts compared to such counts in negative control/Group I (P<0.05) when each administered alone and in combination. Furthermore, results viewed that fisetin significantly increased GSH and SOD1, and decrease MDA levels in serum compared to such levels in CP (Group III) rats (P<0.05). The study concluded that the administration of fisetin alone causes leukopenia and thrombocytopenia and this decrease augmented in combination with CP; while exhibiting a strong antioxidant effect against CP induced-oxidative stress.

Exogenous Apelin-13 Administration Ameliorates Cyclophosphamide- Induced Oxidative Stress, Inflammation, and Apoptosis in Rat Lungs.

Apelin-13 is an endogenous adipocytokine known for its antioxidant, antiinflammatory, and antiapoptotic properties. We aimed to investigate the possible protective effects of exogenous Apelin-13 administration on oxidative stress, inflammation, and apoptosis induced by the cytotoxic agent cyclophosphamide (CP) in the lungs. Twenty-four male Wistar albino rats were divided into four groups: Control (saline), CP (200 mg/kg), Apelin-13 (10 μg/kg/day), and CP+Apelin-13. CP was administered as a single dose on the fifth day, and apelin-13 was administered intraperitoneally for five days. Total oxidant status (TOS), total antioxidant status (TAS), and lipid peroxidation were determined with spectrophotometry, TNFα and IL1β were determined with ELISA, APJ, Sirt1, NF-κB, and p53 mRNA expressions were determined with qRT-PCR, cytochrome (Cyt) C and caspase-3 protein expressions were studied with western blotting in lung tissues. The oxidative stress index (OSI) was also calculated. Furthermore, serum surfactant protein-D (SP-D) and Krebs von den Lungen-6 (KL-6) levels were measured with ELISA. Compared to the control group, TOS, OSI, lipid peroxidation, TNFα, IL1β, cyt C, caspase-3, APJ, NF-κB, and p53 were higher, and Sirt1 was lower in the lung tissue of rats in the CP group. Serum KL-6 and SP-D levels were higher in the CP group. Co-administration of CP with Apelin-13 completely reversed the changes induced by CP administration. Exogenous Apelin-13 treatment protected lung tissue against injury by inhibiting cyclophosphamide-induced oxidative stress, inflammation, and apoptosis. This protective effect of apelin-13 was accompanied by upregulation of the Sirt1 and downregulation of NF-κB/p53 in the lungs.

Neuroprotective effect of quercetin and nano-quercetin against cyclophosphamide-induced oxidative stress in the rat brain: Role of Nrf2/ HO-1/Keap-1 signaling pathway

Quercetin (Qu) is a powerful flavanol antioxidant that is naturally found in plants and is part of the flavonoid family. Qu has a wide range of biological properties, such as neuroprotective, anti-cancer, anti-diabetic, anti-inflammatory, and radical scavenging capabilities. However, the in vivo application of Qu is limited by its poor water solubility and low bioavailability. These issues could be addressed by utilizing Qu nanoformulations. Cyclophosphamide (CP) is a potent chemotherapeutic agent that causes severe neuronal damage and cognitive impairment due to reactive oxygen species (ROS) overproduction. The present study aimed to explore the proposed neuroprotective mechanism of quercetin (Qu) and quercetin-loaded Chitosan nanoparticles (Qu-Ch NPs) against the brain oxidative damage induced by CP in male albino rats. For this aim, thirty-six adult male rats were randomly divided into six groups (n = 6). Rats were pretreated with Qu and Qu-Ch NPs orally in doses of 10 mg/kg bwt/day for 2 weeks, and CP (75 mg/kg bwt) was administered intraperitoneally 24 h before the termination of the experiment. After 2 weeks, some neurobehavioral parameters were evaluated, and then euthanization was done to collect the brain and blood samples. Results showed that CP induces neurobehavioral deteriorations and impaired brain neurochemical status demonstrated by a significant decrease in brain glutathione (GSH), serum total antioxidant capacity (TAC), and serotonin (5-HT) levels while malondialdehyde (MDA), nitric oxide (NO), Tumor necrosis factor α (TNFα), and choline esterase (ChE) concentrations increased significantly compared to the control group. Pretreatment with Qu and Qu-Ch NPs showed a significant anti-oxidative, anti-depressive, and neuroprotective effect through modification of the above-mentioned parameters. The results were further validated by assessing the expression levels of selected genes in brain homogenates and histopathological investigations were done to pinpoint the exact brain-altered regions. It could be concluded that Qu and Qu-Ch NPs can be useful neuroprotective adjunct therapy to overcome neurochemical damage induced by CP.

Effect of Wheatgrass Juice on Fertility Changes Induced by Cyclophosphamide in Male Wistar Albino Rats

In the present study, reproductive toxicity caused by cyclophosphamide on sperm parameters, biochemical parameters, histopathology and protective effect of wheatgrass juice was examined. There were total 6 groups of adult Wistar albino rats. Each group had 6 rats. After 24hrs of the last treatment, rats were sacrificed by cervical dislocation and sperm parameters like sperm count and motility, plasma malonaldehyde (MDA) levels, catalase (CAT) levels, superoxide dismutase (SOD) and glutathione (GSH) activities in testicular tissue, and testicular histopathological changes in the testicular tissue were examined. Administration of cyclophosphamide showed an increase in plasma MDA level and decrease in SOD, GSH and Catalase activity. These values were statistically significant. However, wheatgrass juice treatment along with cyclophosphamide markedly showed improvement in reducing Cyclophosphamide-induced oxidative stress, and normalized sperm characteristics and testicular histopathology. Thus, in conclusion, cyclophosphamide causes fertility changes which leads to male infertility, whereas wheatgrass juice has a protective effect on reversing the testicular damage and male infertility.

Protective effect of arbutin against cyclophosphamide-induced oxidative stress, inflammation, and hepatotoxicity via Nrf2/HO-1 pathway in rats.

Cyclophosphamide (CP) is a potent anticancer drug widely employed in chemotherapy against various types of cancer. However, CP leads to toxicity to non-targeted organs, including the liver and this limits its clinical use. This study explored the role of arbutin (ARB) against CP-mediated oxidative and inflammatory reactions and hepatotoxicity. Rats were administered ARB (25 and 50 mg/kg) for 14 days and CP (150 mg/kg). CP triggered liver tissue injury with marked increase in serum AST, ALT, ALP, and bilirubin, and hepatic malondialdehyde (MDA) and nitric oxide (NO) coupled with diminution of GSH, SOD, catalase, and GPx. Liver NF-kB p65, NOS, IL-6, TNF-α, Bax and caspase-3 were upregulated by CP injection and IL-10 and Bcl-2 were decreased. ARB prevented liver injury, suppressed MDA, NO, NF-kB p65, inflammatory markers, Bax and caspase-3 in CP-treated rats. ARB restored antioxidants, IL-10 and Bcl-2, and enhanced Nrf2 and hemeoxygenase-1 (HO) both gene and protein in the liver of rats. In conclusion, these results pinpointed the protective role of ARB on oxidative and inflammatory reactions, apoptosis, and hepatotoxicity in rats. This hepatoprotective activity was linked to the ability of ARB to modulate Nrf2/HO-1 pathway.

Hepatoprotective effect of taxifolin on cyclophosphamide-induced oxidative stress, inflammation, and apoptosis in mice: Involvement of Nrf2/HO-1 signaling.

Taxifolin (TA) is a natural flavonoid found in many foods and medicinal plants with well-documented antioxidant and anti-inflammatory properties. Cyclophosphamide (CP) is an effective antineoplastic and immunosuppressive agent; however, it is associated with numerous adverse events, including hepatotoxicity. Herein, we aimed to investigate the potential protective effects of TA using a mouse model of CP-induced hepatotoxicity. Mice were co-treated with TA (25 and 50 mg/kg, orally) and CP (30 mg/kg, i.p.) for 10 consecutive days and sacrificed 24 hours later. CP induced increased transaminases (ALT and AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) paralleled with pronounced histopathological alterations in the liver. Moreover, hepatic tissues of CP-injected mice showed increased malondialdehyde (MDA), protein carbonyl, and nitric oxide (NO) levels, accompanied by decreased antioxidant defenses (glutathione [GSH], superoxide dismutase [SOD], and catalase [CAT]). Livers of CP-injected mice also showed increased inflammatory response (nuclear transcription factor kappa-B [NF-κB] p65 activation, increased levels of proinflammatory cytokines tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β], and IL-6) and apoptosis (decreased Bcl-2 and increased Bax and caspase-3 expression levels). Remarkably, TA ameliorated markers of liver injury and histological damage in CP-injected mice. TA treatment also attenuated numerous markers of oxidative stress, inflammation, and apoptosis in the liver of CP-injected mice. This was accompanied by increased nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) expression in the liver tissues of CP-injected mice. Taken together, this study indicates that TA may represent a promising new avenue to prevent/treat CP-induced hepatotoxicity and perhaps other liver diseases associated with oxidative stress and inflammation.

Potential protective effect of escin from Aesculus hippocastanum extract against cyclophosphamide-induced oxidative stress on rat tissues.

Cyclophosphamide (CP)-also known as cytophosphan-is an alkylating agent that has many side effects in humans and rats. Rats were divided into 5 different groups to evaluate the protective effect of escin (ES) obtained from the horse-chestnut plant (Aesculus hippocastanum) against acute damage induce by CP. Groups: control group, ethanol group, ES group (100mg/kg body weight (bw) ES for 14days by gastric gavage), ES+CP group (100mg/kg bw ES for 14days by gastric gavage and 75mg/kg bw CP i.p. on 14th day), and CP group (75mg/kg bw CP i.p. on 14th day). After the experiment was completed, blood and tissue samples (liver, kidney, heart, brain, lung, and testis) were taken from the rats under anesthesia. When the CP group was compared with the control group, an increase was observed in the level of Malondialdehyde (MDA) in blood and all tissues except the lung, but when it was given together with escin, there was a decrease except kidney and lung (P<0.05). Glutathione (GSH) level decreased in the blood and all tissues when CP was given, whereas an increase was observed in the heart, brain, and lung when given with escin (P<0.05). There was no statistical change in the activities of superoxide dismutase and catalase enzymes in all tissues. ES reduced CP-induced damage in all tissues except the kidney. As a result, it was determined that ES had a protective effect against CP-induced tissue damage in rats due to its antioxidant properties.

Olea europaea L leaves and Psidium guajava L. leaves alleviate cyclophosphamide-induced oxidative stress and immune disturbance in Wistar rats

Olea europaea L leaves and Psidium guajava L. leaves alleviate cyclophosphamide-induced oxidative stress and immune disturbance in Wistar rats

Extract-mediated biosynthesis and characterization of gold nanoparticles: Exploring their protective effect against cyclophosphamide-induced oxidative stress in rat testis

The biosynthesis method is essential for minimizing toxic by-products caused by conventional nanoparticle synthesis. Adding a surface biological coating to gold nanoparticles (AuNPs) makes them durable, adaptable, and cost-effective. Herein, Nasturtium officinale leaf extract was used as a reducing and stabilizing agent. UV–vis spectrophotometer, X-ray diffraction, Fourier-transform infrared spectroscopy, transmission electron microscopy, dynamic light scattering, and Zeta potential methods were employed to assess the nanoparticles' formation, crystallinity, size, shape, and surface charge properties. Spherical AuNPs were produced with an average size of 64 nm and demonstrated dose-dependent DPPH scavenging property. To achieve the non-toxic dose of the AuNPs, the MTT assay and AO/PI were performed on the rat bone marrow cells. The co-administration of AuNPs and cyclophosphamide intraperitoneally prevented testicular damages in male rats. In cyclophosphamide-induced gonadotoxicity, the AuNPs' cytoprotective effect was depicted by its reversal of hormonal and morphological alterations toward normality. A reverse transcription-polymerase chain reaction (RT-PCR) analysis was accomplished on apoptotic genes' expression (caspase-3, caspase-9, Bax, Bcl2) to confirm that the biosynthesized nanoparticles could act as a fascinating antioxidant and exert protective effects against apoptosis. These positive results can provide a rational and potential source for a novel conjugation system of chemotherapy drugs with AuNPs in cancer treatment with fewer side effects.

Visualization of peroxynitrite in cyclophosphamide-induced oxidative stress by an activatable probe

Oxidative stress is considered to be one of the main contributors of cyclophosphamide (CP)-induced toxicity, and the generation of free radicals will cause the interruption of multiple signal transduction pathways. Peroxynitrite (ONOO−) has strong oxidation and nitrification ability and is considered as an indirect indicator of oxidative stress. Therefore, it is necessary to design a fluorescent probe that can detect ONOO− and monitor CP-induced oxidative stress during chemotherapy. Herein, we synthesized a lipid droplet targeting fluorescent probe SX-1 based on triphenylamine-benzoindocyanine. When ONOO− is added to the probe SX-1, the CC bond in the probe is broken, thereby releasing fluorescence. The good spectral response characteristics enable SX-1 to successfully track the fluctuations of ONOO− in living cells. Most importantly, we provided the first visual evidence that the level of ONOO− in HeLa cells was up-regulated under CP induction. All results indicated that SX-1 has great potential in detecting drug-induced ONOO−, and provided a new detection tool for a deeper understanding of drug-induced organism injury.

Protective Effects of Small Peptides from Periplaneta americana on Cyclophosphamide-induced Oxidative Stress in Rat Ovaries

Protective Effects of Small Peptides from Periplaneta americana on Cyclophosphamide-induced Oxidative Stress in Rat Ovaries

Renoprotective Effect of Formononetin against Cyclophosphamide-Induced Oxidative Stress and Inflammation in Rat Kidney

Aims: Cyclophosphamide (CP) is a broad-spectrum chemotherapy agent available to treat various malignancies; however, its nephrotoxicity limits its clinical use. Formononetin (FOR) is a bioactive isoflavone with encouraging biological activities. The current study explored and elucidated the possible protective/therapeutic effects of formononetin against CP-induced nephrotoxicity.&#x0D; Methodology: Rats received FOR (40 mg/kg/day) for 15 days followed by a single injection of CP on day 16. CP-induced nephrotoxicity is characterized by an increase in urea and creatinine levels in serum. Kidney homogenate was used to assess MDA, NO and antioxidants.&#x0D; Results: CP-administered rats showed increased renal malondialdehyde and nitric oxide along with declined glutathione and antioxidant enzymes. In addition, CP increased pro-inflammatory cytokines and pro-apoptotic proteins levels and decreased anti-apoptotic protein Bcl2 levels in the kidney. FOR prevented CP-induced kidney injury, enhanced antioxidants and suppressed oxidative stress, pro-inflammatory mediators and apoptosis.&#x0D; Conclusion: These findings suggest that FOR prevents CP nephrotoxicity by attenuating the oxidative damage and inflammation. Therefore, our data suggest that FOR may represent a novel protective strategy against CP-induced nephrotoxicity, which deserves pursuit in further studies.

Antioxidant and antigenotoxic properties of Alpinia galanga, Curcuma amada, and Curcuma caesia

Objective: To compare the antioxidant and anti-genotoxic properties of Alpinia (A.) galanga, Curcuma (C.) amada, and C. caesia.Methods: Cytotoxicity of ethanolic extracts of A. galanga, C. amada, and C. caesia at selected doses was evaluated by trypan blue, MTT, and flow cytometry-based assays. Genotoxicity and anti-genotoxicity (against methyl methanesulfonate, 35 μM and H2O2, 250 μM) of these plants were studied by comet assay in human lymphocytes in vitro. Furthermore, DPPH, ABTS, FRAP, lipid peroxidation, and hydroxyl radical scavenging assays were performed to study the antioxidant potentials of the plants. Finally, anti-genotoxic potential of C. amada was validated in Swiss albino mice using comet assay. Phytochemical composition of C. amada was determined by GC/MS and HPLC.Results: The selected doses (2.5, 5, and 10 μg/mL) of A. galanga, C. amada, and C. caesia were non-toxic by cytotoxicity tests. All three ethanolic extracts of plant rhizomes demonstrated antioxidant and anti-genotoxic properties against methyl methanesulfonate-and H2O2-induced oxidative stress in human peripheral blood lymphocytes in vitro. Multivariate analysis revealed that various antioxidant properties of these extracts in DPPH, ABTS, and FRAP assays were strongly correlated with their total phenolic constituents. C. amada extract conferred protection against cyclophosphamide-induced DNA damage in the bone marrow cells of mice and DNA damage was significantly inhibited by 2.5 mg/kg C. amada extract.Conclusions: C. amada is rich in potentially bioactive molecules and exhibits potent antioxidant activities. Its anti-genotoxicity against cyclophosphamide-induced oxidative stress is also confirmed in this study.

Effect of Datura stramonium on Cyclophosphamide-induced Oxidative Stress in Albino Rats: Study on Kidney Markers

Effect of Datura stramonium on Cyclophosphamide-induced Oxidative Stress in Albino Rats: Study on Kidney Markers

Nerolidol ameliorates cyclophosphamide-induced oxidative stress, neuroinflammation and cognitive dysfunction: Plausible role of Nrf2 and NF- κB

AimCyclophosphamide (CP) is a potent anticancer and immunosuppressant drug. Studies have shown significant oxidative stress and cognitive impairment but neuroinflammatory and histological aberrations with its administration is underexplored. Nerolidol (NER) is a lipophilic bioactive molecule with antioxidant and anti-inflammatory properties but it has not been explored for neuroprotective potential in CP-induced neurotoxic manifestations. Therefore, in the present study, we aimed to evaluate the neuroprotective potential of NER in CP-induced neuroinflammation and associated comorbid conditions like depression and cognitive dysfunctions. Materials and methodIn-silico study using Schrödinger software was used to assess the binding affinity of NER with Nrf2. In the In vivo study, NER 200 and 400 mg/kg p.o. were given from 1st day to 14th day. CP 200 mg/kg, i.p., was administered on the 7th day. After 24 h of the last dosing, neurobehavioral tests like spontaneous body alternation, passive avoidance and forced swim test were performed. On completion of study, mice were sacrificed, hippocampus and cortex were removed for biochemical estimations, histopathology and immunohistochemistry of p65 NF- κB and Nrf2. Key findingsIn-silico study showed significant binding of NER into the pocket domain of Nrf2. In-vivo study showed protective effect of NER against CP-induced neuroinflammation, oxidative stress, cognitive impairment and structural abnormalities in the hippocampus and cortex regions. SignificanceFindings of the study suggested that NER is a potential therapeutic molecule which can mitigate CP-induced neurotoxic manifestations via Nrf2 and NF-κB pathway. However, more detailed studies are needed to explicate the mechanism underlying its neuroprotective effect.

Protective effects of Nostoc sphaeroides Kütz against cyclophosphamide-induced immunosuppression and oxidative stress in mice

Nostoc was orally administered to mice to evaluate the possible effects on cyclophosphamide (CY)-induced immunosuppression. The results showed that feeding Nostoc may promote the growth of mice. Meanwhile, spleen and thymus indices, WBC, splenic lymphocyte transformation rate, macrophage phagocytosis, and T-AOC were significantly higher in mice treated with CY + Nostoc than treated with CY. ELISA results showed that Nostoc treatment enhanced the production of IgG, IL-2, IL-4, and IFN-γ in sera of CY-treated mice. In addition, histopathological examination confirmed the biochemical and immunological results, suggesting that Nostoc may be a promising modulator in attenuating CY-induced immunosuppression and oxidative stress.

Olea europaea leaf extract up-regulates Nrf2/ARE/HO-1 signaling and attenuates cyclophosphamide-induced oxidative stress, inflammation and apoptosis in rat kidney

Olive leaf extract (OLE) has potential health benefits and protects against cytotoxicity in different organs. However, nothing has yet been reported on its potential to prevent cyclophosphamide (CP)-induced nephrotoxicity. This study investigated the possible protective effect of OLE on CP-induced kidney injury in rats, focusing on oxidative stress, inflammation, apoptosis and Nrf2/ARE/HO-1 signaling. Rats received 100 or 200 mg/kg body weight OLE for 15 days and a single injection of 150 mg/kg CP at day 16. CP induced kidney injury evidenced by the significantly increased serum creatinine and urea, and histopathological alterations, including glomerular atrophy, interstitial hemorrhage, dilated urinary space and necrosis. CP-induced rats exhibited increased kidney lipid peroxidation, protein carbonyl, nitric oxide (NO) and pro-inflammatory cytokines, and up-regulated NF-κB, Bax, cytochrome c and caspase-3. OLE ameliorated kidney function markers and prevented CP-induced tissue damage. In addition, OLE significantly prevented oxidative stress, inflammation and apoptosis by enhancing the antioxidant defenses and Bcl-2 expression, and suppressing the pro-inflammatory and pro-apoptotic markers NF-κB, Bax, cytochrome c and caspase-3. OLE up-regulated Nrf2, HO-1 and NQO-1 expression in the kidney of CP-induced rats. In conclusion, OLE has a substantial protective role against CP-induced nephrotoxicity in rats by up-regulating the Nrf2/ARE/HO-1 signaling, enhancing the antioxidant activity and attenuating inflammation and apoptosis.

Camel milk exosomes modulate cyclophosphamide-induced oxidative stress and immuno-toxicity in rats.

Camel milk proteins exhibit many beneficial properties including immuno-modulatory and anti-oxidant effects. Recent studies demonstrated that most of these properties are ascribed to the presence of extracellular nanovesicles known as exosomes. Therefore, the current study aimed to investigate the effect of the immuno-modulatory and anti-oxidant properties of camel milk exosomes on the immuno-toxicity and oxidative stress induced by cyclophosphamide (CTX) in albino rats. Exosomes were isolated from camel milk and exosomal kappa casein and lactoferrin mRNAs were detected and then sequenced. CTX was used to induce immunosuppression in rats, which were further treated with camel milk and its exosomes. The alterations in biochemical parameters, antioxidant status, cytokine profile, spleen histopathology and flow cytometric analysis were detected. Treatment with CTX resulted in a significant decrease in total protein, albumin, globulin, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels associated with a significant increase in the levels of malondialdehyde (MDA) when compared with the control group. Moreover, CTX depleted lymphocytes in the spleen tissue, significantly reduced the expression of interferon gamma (IFN-γ) in the spleen cells and decreased the CD4+ and CD8+ cell percentages in the blood and spleen, while it induced a significant increase in the expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Co-administration of camel milk exosomes was able to normalize the antioxidant status and most of the biochemical and immunological parameters. This study clarifies that camel milk and its exosomes successfully ameliorate immunosuppression and oxidative stress induced by CTX in rats.

Boric acid protects against cyclophosphamide-induced oxidative stress and renal damage in rats

The worldwide increase in the rate of cancer incidence also leads to a significant increase in the use of chemotherapeutic agents. Unfortunately, the optimal clinical usefulness of these agents is heavy restricted by a high incidence of several organ toxicity and as well reason oxidative stress and bring about changing in antioxidant status. Kidney toxicity is a side effect often encountered with cyclophosphamide (CPM) which is commonly used in most cancer chemotherapy. The present study aims on the assessment of the probable defensive efficacy of Boric acid (BA) against CPM-induced oxidative stress and renal damage in rats. Based upon our investigation results with oxidative stress markers and light microscopic findings, it can be concluded that BA significantly reduced CPM induced oxidative stress and renal damage. As far as we know, high dose (200 mg/kg) of BA are the first study on the prevention of kidney damage caused by CPM. It is thought that the renoprotective effects of BA may be due to an increase in the activity of the antioxidant protection system and also inhibition of lipid per oxidation.