Protective effects of garlic extract against hematological alterations, immunosuppression, hepatic oxidative stress, and renal damage induced by cyclophosphamide in rats.

Cyclophosphamide is an alkylating agent widely used as anticancer drug, reported to exert cytotoxic effects attributed to oxidative stress. Therefore, this study aimed to explore the protective effect of ethanolic extract of garlic (EEG) against cyclophosphamide (Cyp)-induced hematological disturbance and immunosuppressive and hepatotoxic effects. Forty male Wistar albino rats were randomized into four equal groups: the normal control one, the Cyp-treated group (50 mg/kg BW/IM, once weekly), the EEG-treated group (300 mg/kg BW, orally, daily), and the Cyp & EEG group. All rats received their relevant treatments for four consecutive weeks. This study revealed that Cyp significantly decreased erythrocyte count, hemoglobin (Hb), packed cell volume (PCV), and total leukocyte and lymphocyte counts. However, the counts of neutrophils, eosinophils, and toxic neutrophils were elevated. Additionally, hepatic malondialdehyde (MDA) and levels of liver and renal biomarkers were significantly elevated in the Cyp-treated group. Otherwise, hepatic catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD), and serum total antioxidant capacity (TAC) were significantly lower than the control rats. Furthermore, Cyp significantly reduced whole blood respiratory burst activity (NBT), serum lysozyme and bactericidal activities, interlukin-12 (IL-12), and interferon-γ. In contrast, the levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interlukin-1ß (IL-1ß) were elevated. Additionally, Cyp induced hepatic and renal histopathological alterations. Data in the present study demonstrated that EEG has immunomodulatory and antioxidant effects and has the ability to diminish the alterations induced by Cyp.

3D printing and coating to fabricate a hollow bullet-shaped implant with porous surface for controlled cytoxan release.

Intratumoral implants have aroused great interests for local chemotherapy of cancer, however, how to efficiently control drug release from implants is still a great challenge. Herein, we designed and prepared a new hollow bullet-shaped implant with porous surface by 3D printing, loaded chemotherapeutic agent cytoxan (CTX) with tetradecyl alcohol or lecithin as matrix and coated it with poly (lactic acid) to obtain a CTX implant, which has a highly tuned drug release property with a drug release time from 4 h to more than 1 month. The drug release from the implant can be easily controlled by changing pore sizes, kinds of matrices, and coating thickness.

A homogalacturonan from Hippophae rhamnoides L. Berries enhance immunomodulatory activity through TLR4/MyD88 pathway mediated activation of macrophages.

Our previous study isolated a natural high-methoxyl homogalacturonan (HRWP-A) from Hippophae rhamnoides and showed antitumor activity in vivo. In this study, the immunomodulatory activity and mechanisms of action of HRWP-A were further investigated. Results showed that HRWP-A could recover the body condition and activated macrophage in Cyclophosphamide (CTX)-induced immunosuppressed mice. Further, we investigated the possible mechanism underlying the effects of HRWP-A on mouse peritoneal macrophages. qPCR and western blot revealed that HRWP-A upregulated the expression of TLR4 mRNA in vitro. This process was accompanied by a clear increase in MyD88 expression and p-IκB-α, but these effects were largely abrogated by pretreatment with anti-TLR4 antibodies. The effects of HRWP-A on macrophage NO, IL-1ß and IL-6 production were also inhibited by anti-TLR4 antibodies and were greatly influenced by the NF-κB inhibitor PDTC. Moreover, HRWP-A failed to induce the production of NO, IL-1ß and IL-6 in peritoneal macrophages prepared from C3H/HeJ mice, which have a point mutation in the Tlr4 gene, suggesting the involvement of the TLR4 molecule in HRWP-A-mediated macrophage activation. These results may have important implications for our understanding of the structure-activity relationship of immunopotentiating polysaccharides from medicinal herbs.

Antioxidant potential of Phyllanthus fraternus Webster on cyclophosphamide induced changes in sperm characteristics and testicular oxidative damage in mice.

Cyclophasphamide (CPA) is used to treat various types of cancer. It is a cytotoxic alkylating agent widely used in chemotherapeutic regimen. However, the clinical efficacy of CPA is marred by its side effects. In clinical applications of CPA, it becomes necessary to prevent the oxidative stress and reproductive toxicity induced thereby in normal cells. In the present study, we investigated the protective effect of aqueous extract of Phyllanthus fraternus (AEPF) on CPA (200 mg/kg body wt., i.p.) induced changes in sperm characteristics and testicular oxidative damage in male mice. The CPA treated group showed significant decrease in gonadosomatic index (GSI), epididymal sperm count, sperm motility and sperm viability compared to control group, while the CPA + AEPF treated group had significant increase with respect to these variables compared to the CPA-treated group. The elevated levels of lipid peroxidation by CPA were effectively reduced with AEPF. It also exhibited protective action against the CPA induced depletion of antioxidants like catalase and superoxide dismutase. DNA damage was measured by comet assay, biomonitoring with comet assay elicited significant increase in genotoxicity. Genotoxicity caused by CPA was counteracted by aqueous extract of Phyllanthus fraternus. Administration of the plant extract along with CPA restored the histopathological architecture of testis. Thus, the aqueous extract of P. fraternus by virtue of its antioxidant potential can be used as an effective agent to reduce CPA-induced oxidative stress in male mice.

Topical treatment of cutaneous vaccinia virus infections in immunosuppressed hairless mice with selected antiviral substances.

BACKGROUND: Certain nucleoside, nucleotide and pyrophosphate analogues may be useful for treating severe complications arising as a result of virus dissemination following smallpox (live vaccinia virus) vaccinations, especially in immunocompromised individuals. We used an immunosuppressed hairless mouse model to study the effects of 10 antiviral agents on progressive vaccinia infections. METHODS: Hairless mice were immunosuppressed by treatment with cyclophosphamide (100 mg/kg) every 4 days starting 1 day prior to vaccinia virus (WR strain) infection of wounded skin. Topical treatments with antiviral agents were applied twice a day for 7 days starting 5 days after virus exposure. RESULTS: Topical 1% cidofovir cream treatment was effective in significantly reducing primary lesion severity and decreasing the number of satellite lesions. Topical 1% cyclic HPMPC and 1% phosphonoacetic acid were not quite as active as cidofovir. Ribavirin (5%) treatment reduced lesion severity and diminished the numbers of satellite lesions, but the mice died significantly sooner than placebos. 2-Amino-7-[(1,3,-dihydroxy-2-propoxy)methyl]purine (compound S2242; 1%) moderately reduced primary lesion sizes. Ineffective treatments included 5% arabinosyladenine, 1% arabinosylcytosine, 1% 5-chloro-arabinosylcytosine, 5% arabinosylhypoxanthine 5-monophosphate and 5% viramidine. CONCLUSIONS: Of the compounds tested, topically applied cidofovir was the most effective treatment of cutaneous vaccinia virus infections in immunosuppressed mice. Topical treatment with cidofovir could be considered as an adjunct to intravenous drug therapy for serious infections.

Drug targeting and metabolic investigations of cryoprepared tumor cells with analytical electron energy loss spectroscopy.

Analytical electron microscopy is an ideal tool for holistic data acquisition on biological systems. The use of analytical electron microscopy for both, the investigation of micropharmacokinetic problems and metabolic studies, is becoming more and more important. Depending on the mode of investigation, it is possible to localize drugs and xenobiotics precisely in situ under optical control or to quantify their uptake and distribution in the corresponding target cells without disintegrating the cell or tissue material. In this paper, we present instructive examples for the application of analytical electron energy loss spectroscopy in transmission electron microscopy in order to investigate the cellular uptake and distribution of cisplatin and cyclophosphamide and the metabolic changes induced by an alteration in the extracellular calcium concentration in a holistic manner.