The pharmacokinetics of conventional and long-acting (LA) oxytetracycline (OTC), widely used broad-spectrum antibacterial drugs in veterinary medicine, were evaluated in Kilis goats at single dosage of 20 mg/kg body weight (bw). A total of 21 goats were divided into three groups: intravenous (Group I) and intramuscular (IM) (Group II) administration of the conventional formulation and IM administration of the LA formulation (Group III). Blood samples were taken at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, and 96 h; and OTC analysis was performed by HPLC. For Group III and Group II, time to reach maximal plasma drug concentration (Tmax) was 0.6 ± 0.28 and 0.46 ± 0.09 h and maximal plasma drug concentrations (Cmax) were 8.72 ± 2.47 μg/ml and 13.57 ± 5.83 μg/ml, respectively. In Group I, C0 concentration was found to be 63.51 ± 11.59 μg/ml. The elimination times (T1/2) were 10.84 ± 3.20, 27.96 ± 11.66, and 10.47 ± 1.30 h; and AUC were 115 ± 29.12, 96.44 ± 9.49, and 80.86 ± 12.76 μg/ml/h for Group I; Group II, and Group III, respectively. Bioavailability by IM administration were 69.71% for the conventional OTC and 83.15% for the LA OTC.
Artemisinin, an antimalarial drug, has anticancer activity and possesses protective effects against several tissue injuries. The aim of the present study was to investigate the effects of artemisinin on doxorubicin-induced renal and testicular toxicity in rats. Doxorubicin was administered to rats at a single dose of 10 mg/kg body weight (b.w.) as a single intraperitoneal injection. Application of artemisinin was by using oral gavage feeding needle for 14 days at different specified doses (7 mg/kg and 35 mg/kg b.w.). At the end of the experiments, kidney and testis samples were collected and used for histopathological and immunohistochemical examinations. At histopathological examination, while hyperemia was the marked finding in kidney and testis of rats treated with doxorubicin only, no evidence of structural abnormalities showed in other groups. Immunohistochemical examination of the testes and kidneys demonstrated significantly increased expression of caspase-3, TNF-α, iNOS and NF-κB in rats treated with doxorubicin only. Artemisinin decreased the doxorubicin-induced overexpression of NF-κB, iNOS, TNFα and caspase-3 in these tissues of rats. Artemisinin can protect the kidney and testis against doxorubicin-induced nephrotoxicity and testotoxicity, probably through a decrease of caspase-3, TNF-α, iNOS and NF-κB expressions. It may be concluded that artemisinin has a potential for clinical use in the treatment of kidney and testis damage induced by doxorubicin. Further researches are required to determine the appropriate combination of artemisinin with doxorubicin.
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