BACKGROUND: Doxorubicin is one of the most widely used anticancer chemotherapeutic agents in small animal practice. The use of doxorubicin can cause cardiotoxicity, hepatotoxicity, neurotoxicity, and nephrotoxicity. OBJECTIVES: This study was carried out to evaluate the effects of ascorbic acid on doxorubicin hepatotoxicity in mice. METHODS: Twenty-four Balb/c mice were randomly divided into four groups. Group one received normal saline, group two received 100 mg/kg ascorbic acid, group three received 8 mg/kg doxorubicin and group four received ascorbic acid and doxorubicin intraperitoneally, with the same doses of groups 2 and 3. Twenty-one days after injection, the mice were euthanized. The activities of ALP, ALT, AST enzymes and total bilirubin levels in the serum samples were measured. Liver samples were evaluated histopathologically. RESULTS: The activities of ALP, ALT, AST, and total bilirubin levels and histopathologic scores of hepatotoxicity were significantly lower in the group that received ascorbic acid + doxorubicin in comparison to those of the doxorubicin group. CONCLUSIONS: Ascorbic acid may be useful in the prevention of doxorubicin hepatotoxicity in mice. Further studies are recommended for evaluation of the use of ascorbic acid in small animals.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women. One in eight women will be diagnosed with breast cancer in their lifetime. Chemotherapy works on active cells. Active cells are cells that are growing and dividing into more of the same type of cell. Cancer cells are active, but so are some healthy cells. Also, scientists work constantly to develop ways of providing treatment with fewer chemotherapy side effects. Objectives: The aim of this study was antitumor effect of simultaneous low-intensity, 150 kHz ultrasound, in combination with the reduced dose of anticancer drug Doxorubicin (DOX) on breast adenocarcinoma using murine model (BALB/c). Methods: Twenty-five female BALB/c mice were used in this study. The tumor was implanted under the breast skin of mice. Mice were divided into five groups, namely control, sham, drug (IV injected of 2 mg/kg of DOX), drug (IV injected of 1 mg/kg of DOX) + US (150 kHz for 15 minutes) and exposure to ultrasound (150 kHz for 15 minutes) alone. The data were analyzed employing ANOVA using SPSS software V.13 and complementary test of Tooki was done. Results: It was shown that, after injection of DOX, exposure to ultrasound at 150 kHz the necrotic spaces in adenocarcinoma tumors compared to control and sham groups have meaningful variance (p<0.001). There was also a significant difference (the bigger the necrotic spaces) between the drug+US group and drug treated group (p<0.05), It should be mentioned that the dose of DOX in drug+US group was reduced to 1mg/kg. Conclusions: The co-administration of DOX and low-intensity ultrasound provided a more effective treatment than the drug alone in murine adenocarcinoma breast cancer. The combined treatment appeared to produce synergistic effects that could prove potentially useful in reducing the side effects of DOX by lowering the required effective dose of the drug while increasing the efficiency of the therapy as a whole.

Introduction: Due to the high heterogeneity of canine lymphoma, the aim of the present study was to test in vitro the chemosensitivity of canine high-grade primary lymphoma cells to various cytostatic drugs commonly used to treat dogs: 4-HO-cyclophosphamide, doxorubicin, dexamethasone, prednisolone, vincristine, etoposide, chlorambucil, lomustine, and cytosine arabinoside. Material and Methods: To determine the cell viability and drug ability to induce apoptosis two different tests were used: an MTT assay and annexin V/propidium iodide staining. Results: Both in vitro tests were found to be useful tools. Significant differences in the sensitivity, depending on the drug type, between B-, T- and mixed/null-type lymphoma cells were found for the majority of the tested drugs. B-type cells were the most sensitive in vitro, whereas T-type cells seemed to be the most resistant. Doxorubicin, chlorambucil, etoposide, and vincristine most strongly reduced the cell viability and induced apoptosis. Conclusion: In vitro assays, such as the MTT test and especially the annexin V/PI assay, may be useful tools for predicting a response to the treatment of high-grade lymphoma in dogs or improving the treatment outcomes in individual animals.

The proposed advantages of intra-arterial chemotherapy (IAC) are based on the premises of local dose escalation to the tumor and reduced availability of systemic drugs. There is a lack of objective pharmacokinetic data to confirm the advantage of IAC in dogs with naturally occurring urogenital tumors. The objective of this study was to determine if IAC administration in urogenital tumors would result in decreased systemic drug exposure when compared to intravenous routes. Twenty-two dogs with naturally occurring urogenital tumors were enrolled in this prospective case-controlled study. Mitoxantrone, doxorubicin, or carboplatin were administered by IAC and intravenous routes [intravenous awake (intravenous chemotherapy - IVC) and under general anesthesia (IVGAC)] 3 weeks apart. Serum assays were used to determine the extent of systemic drug exposure. Dose-normalized peak systemic serum concentration (Cmax) and area under the serum drug concentration-time curve (AUC) were used to quantify systemic exposure. A total of 26 mitoxantrone treatments were administered to 10 dogs. While there was no significant difference in Cmax, the AUC was significantly lower after IAC compared with IVGAC. Ten doxorubicin treatments were administered to 5 dogs. There were no significant differences in Cmax or AUC. A total of 14 carboplatin treatments were administered to 7 dogs. The Cmax was significantly lower for IAC compared to IVC, while the AUC values were equivocal. This study demonstrates certain lower serum values may be achieved after IAC delivery of carboplatin and mitoxantrone. These chemotherapy agents may have a preferred pharmacological profile for regional chemotherapy delivery in dogs with urogenital tumors.

A rapid, simple chemosensitivity assay, assessing tumor cell nuclear uptake of doxorubicin hydrochloride, was evaluated in 16 dogs with appendicular osteosarcoma. Doxorubicin was administered to dogs in 5 biweekly treatments, and surgical resection was performed after the second or third treatment, The chemosensitivity assay was performed on biopsy specimens from all dogs before chemotherapy. It was repeated on tissue from resected tumors, and tumors were evaluated histologically to determine the degree of necrosis resulting from chemotherapy. Disease-free and total survival time correlated significantly (P < 0.05 in both cases) with the degree of postchemotherapy necrosis of the primary tumors. Significant correlation was not apparent between the percentage of tumor cells with nuclear uptake of doxorubicin (in either biopsy or resection samples) and disease-free or total survival time. The percentage of cells with nuclear uptake of doxorubicin in surgically resected tumors correlated significantly (P < 0.05) with percentage of necrosis,

Natural killer (NK) cell activity and function were determined for 11 untreated and treated dogs with lymphoma. Concurrent chromium release and single cell binding assays, methods used to measure overall cytotoxic activity and that from individual cells, respectively, were performed at effector-to-target cell ratios of 50:1 and 100:1, with incubation periods of 12 and 16 hours. Significant reduction was achieved in overall activity for untreated dogs, using a 16-hour incubation period and an effector-to-target ratio of 100:1 (P less than 0.05). Decreased activity (P less than 0.025) was also achieved for those dogs that were administered combination chemotherapy, consisting of such drugs cyclophosphamide, vincristine, prednisone, and doxorubicin. There was no significant difference in binding or cytotoxin activity by individual cells in the untreated or treated dogs, compared with the healthy controls. Short- or long-term treatment with glucocorticoids did not influence overall NK cell activity or individual cell cytotoxicity. The overall cytotoxic activity in untreated dogs was reduced, but these dogs had relatively normal numbers of NK cells compared with paracontrols. This suggests that a defect in recycling, or the ability to kill targets repetitively, may be involved. A similar defect was found in NK cells of dogs treated aggressively with combination chemotherapy.

The present study was designed to evaluate the probable ameliorative effect of dandelion extract against doxorubicin hemato-cardiotoxicity. To accomplish this study, four groups of male albino rats (n=7) were used as follow, Group I: served as a control group, Group II: received dandelion extract (200 mg/ kg), Group III: received doxorubicin (2.5 mg/kg) and Group IV: received dandelion extract and doxorubicin identically to groups II and III. Doxorubicin was administrated 3times/week for two consecutive weeks, while dandelion extract was administrated daily for two consecutive weeks before doxorubicin administration and continued during doxorubicin treatment. The results illuminated that, administration of doxorubicin has a deleterious effect on both of blood cellular components and cardiac tissues, which was indicated by significant pancytopenia (decrease in all blood cell types), elevated serum cardiac enzymes activity (CK-MB and LDH), increased serum level of cardiacrelated proteins (troponin I, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) with a depletion of cardiac tissues antioxidant (GSH, and SOD enzyme) and elevated lipid peroxide (MDA) level in this tissues. Coadministration of dandelion extract with doxorubicin significantly alleviated its hemato-cardiotoxic effect which was reflected positively on hematobiochemical changes and cardiac histopathological alterations.

TVT, also known as infectious sarcoma, venereal granuloma, transmissible lymphosarcoma or sticker tumour is a benign reticuloendothelial tumour that affects particularly mucosa of external genital organs and rarely internal genital organs in dogs of both genders. TVT is usually transmitted by coitus but also can be transmitted by licking, sniffing, biting,and scrabbling of the tumour affected area or through damaged skin of mucosa. Transmissible venereal tumour (TVT) is usually observed in stray animals live in tropical and subtropical lands. The affected animals are usually within 9-13 months of age and with high sexual activity. Tumour is frequently located in posterior vagina and vestibulovaginal junction. The averagechromosome count of TVT cells is 59 (57- 64). TVT specific antibodies were found in blood samples of affected animalswhich suggest that they may have a role in natural regression mechanism. The primary objective of tumour treatment is total elimination by surgery, radiotherapy, immunotherapy and/or chemotherapy. Controlling of the disease is very difficult because stray dogs are carriers.

Doxorubicin was encapsulated in canine erythrocytes, treated with 0.32% glutaraldehyde, and administered at a dosage equivalent to 30 mg of free doxorubicin/m(2) of body surface area to dogs with diagnosis of lymphosarcoma. Compared with administration of free doxorubicin, this method of drug delivery substantially reduced peak plasma concentration and prolonged higher plasma concentration of doxorubicin. As such, this method was comparable to continuous IV infusion. Previous studies have indicated this method's potential for reduction in toxic side effects, particularly cardiotoxicosis, while allowing higher total doses of doxorubicin to be administered. In this study, doxorubicin encapsulated in glutaraldehyde-treated erythrocytes induced a triphasic exponential decay of doxorubicin from plasma, the highest relative contribution to the total area of the curve being the terminal phase. The treatment was effective in inducing complete and partial remissions of lymphosarcoma, with minimal acute toxicosis and no evidence of cardiotoxicosis. However, substantial, unanticipated, chronic, nonregenerative myelosuppression developed, and was most strikingly expressed as profound thrombocytopenia. Efforts to ameliorate or circumvent this toxic effect will be required prior to further consideration of this doxorubicin delivery system for treatment of systemic neoplasia.

Clinical remission in 30 dogs with lymphoma was induced with a combination of vincristine, L-asparaginase, cyclophosphamide, and doxorubicin HCl, administered sequentially, and then an autochthonous tumor cell vaccine, given intralymphatically, as maintenance therapy. Humoral antibody amounts were monitored in 11 dogs, using a solid-phase bead-type radioimmunoassay. The median survival of the 30 dogs was 13 months from the start of chemotherapy (range, 7 to 25 months; mean, 13.8). The median remission duration was 16 weeks (range, 9 to 98 weeks; mean, 26.8). Correlation between increase in amount of humoral antibody was significant (P = 0.0001 to 0.012), before and after chemoimmunotherapy, in dogs responding to therapy compared with that in dogs not responding to therapy.