The effects of chrysin on lipopolysaccharide-induced sepsis in rats.

Chrysin (CR) is a flavone found in propolis and many plants. Lipopolysaccharide (LPS) is a component of the cell wall of gram-negative bacteria that causes sepsis. The purpose of this study was to investigate the effects of CR on LPS-induced sepsis in rats. LPS intraperitoneal and a single dose and CR were given orally for 10 days. Rats were sacrificed, blood samples were taken, liver, lung, and kidney tissues were dissected, homogenized, and histopathological analysis was carried out. When CR groups compared to sepsis group, CR significantly decreased the serum levels of aspartate transaminase (AST) and alanine aminotransferase (ALT), interleukin-1 beta (IL-1ß), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and levels of malondialdehyde (MDA) in tissues. CR also increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in tissues. Histopathological findings were consistent with biochemical findings. Conclusion, CR could reduce the oxidative stress markers and cytokines in sepsis. PRACTICAL APPLICATIONS: Our approach is to determine the antioxidant and anti-inflammatory effects of chrysin, known as a flavolonoid, which are found in many plants and foods such as honey and propolis. In this study, experimental sepsis model was created using LPS. According to the results of the study, CR can attribute to the ameliorating of oxidative damage in tissues (lung, liver, and kidney) and it can suppress the sepsis-associated acute tissue injury via reduction of inflammation in rats. Even, CR can be used as a pharmacological agent in inflammatory diseases caused by other sources and in many cases causing oxidation.

Effects of cypermethrin, propetamphos, and combination involving cypermethrin and propetamphos on lipid peroxidation in mice.

Insecticides are the chemicals widely used in agriculture, environmental health, human-and animal-health fields. Exposure to insecticides has been associated with many hazardous effects, including antioxidative metabolism. In the current study, the effect of cypermethrin (CYP), propetamphos (PRO) and their mixtures on oxidative stress in mice to understand the possible health effects to animals and human beings was investigated. In the present study, 245 male Albino mice weighing 35-40 g were used. The mice were divided into seven groups. The first group served as the control group. The second and third groups were administered CYP at doses of 5 mg/kg/bw and 10 mg/kg/bw, respectively, and the fourth and fifth groups were given PRO at doses of 2.5 mg/kg/bw and 5.0 mg/kg/bw, respectively. The sixth and seventh groups received combination regimens containing 5 mg/kg/bw CYP plus 2.5 mg/kg/bw PRO and 10 mg/kg/bw CYP plus 5 mg/kg/bw PRO, respectively, in feed for 60 days. Blood samples were collected by cardiac puncture on the 15th, 45th and 60th days. Serum nitric oxide (NO) and plasma malondialdehyde (MDA) levels and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were measured. In conclusion, the alterations observed in the MDA and NO levels and SOD, CAT, and GSH-Px activities of the trial groups, demonstrate the administration of certain doses of CYP and PRO, either alone or combined, to mice for a period of 60 days to produce oxidative stress. The degree of oxidative stress was found to be related to the dose administered, the duration of exposure and the administration of the indicated compounds either alone or as a combination.

Comparative pharmacokinetics of some injectable preparations containing ivermectin in dogs.

Little is known about the kinetics of ivermectin formulations following subcutaneous administration in dogs. The vehicle components used in production may change the pharmacokinetics of the drug. The present study was aimed at the comparison of the pharmacokinetics of seven injectable ivermectin formulation of different brand names (A-G). The animals were allocated to seven groups, each comprising seven dogs. The dogs were administered ivermectin at a dose of 200 microg/kg bw by subcutaneous route and blood samples were collected from all groups up to 288h post-injection. Plasma ivermectin analyses were performed using a HPLC with a fluorescence detector. Compared to Group 1(A), it was determined that statistically significant differences existed in Groups 2(B), 3(C), 4(D), 5(E), and 7(G) for C(max) values; and in Groups 3(C), 4(D), 6(F), 7(G) for AUC(0-->288) and AUC(0-->infinity) values. These values were highest in Group 1(A) and lowest in Group 7(F). The results obtained in the present study demonstrated that, in cases which require subacute administration, optimal exposure is achieved with the preparation A. However, it must be noted that this evaluation was based on pharmacokinetic parameters and not antiparasitic efficacy.

The effects of royal jelly on liver damage induced by paracetamol in mice.

The present study was undertaken to investigate the protective effect of royal jelly against paracetamol-induced liver damage. The study was conducted in 90 female Swiss Albino mice, and six groups were established. While the first group was maintained as control, Groups 2-6 were administered 200mg/kg RJ for 1 day, 200mg/kg RJ for 7 days, 400mg/kg PAR for 1 day, 200mg/kg RJ plus 400mg/kg PAR for 1 day and 200mg/kg RJ for 7 days and then second 400mg/kg PAR on the 7th day, orally, respectively. It was shown that PAR significantly increased serum ALT, AST, ALP, liver MDA levels and significantly decreased liver GSH-Px activity, when compared to the control group (Group 1). On the other hand, meaningful changes were observed in the biochemical parameters of the group which was administered long-term RJ (Group 6). The aforementioned parameters which were statistically significant were determined to have drawn closer to values of the control group, and among these, the existing statistical differences for MDA level and GSH-Px activity between the trial group (Group 6) and the control group disappeared (Group 1). Compared to the pathological changes observed in the liver parenchyma, remark cords, sinusoids and hepatocytes in the group which was administered paracetamol alone (Group 4), lesions were determined to be less severe particularly in the group (Group 6) which received royal jelly for 7 days prior to paracetamol. In conclusion, the administration of royal jelly as a hepatoprotective agent for 7 days against paracetamol-induced liver damage was determined to exhibit marked protective effect on liver tissue.

Eimeria stiedae: experimental infection in rabbits and the effect of treatment with toltrazuril and ivermectin.

The aim of this study was to investigate the clinical, haematological, biochemical, lipid peroxidation, ultrasonographic and pathologic findings in hepatic coccidiosis induced by Eimeria stiedae in rabbits, and also to compare the treatment effects of both toltrazuril and ivermectin separately and in combination. In this study, 56 rabbits were divided into eight groups. The first group was designated as healthy control group. Rabbits were infected with 40.000 sporulated oocysts of E. stiedae. Groups 2, 3, 4, 5, 6, 7 and 8 were allocated as the infected control group, infected+toltrazuril-treated group, infected+ivermectin-treated group, infected+toltrazuril+ivermectin-treated group, non-infected+toltrazuril-treated group, non-infected+ivermectin-treated group, non-infected+toltrazuril+ivermectin-treated group, respectively. Haematocrit, Haemoglobin and MCV values as well as percentage of lymphocyte decreased in Groups 2 and 4 whereas leucocyte counts and percentage of granulocyte leucocyte increased. Serum GGT, ALT and AST activities increased but albumin value decreased. Plasma MDA concentrations increased whereas erythrocyte CAT, GSH-Px, and SOD activities decreased. Mean oocyst numbers in per gram faeces (epg values) increased in both groups during the study. Ultrasonographic examination revealed that the liver was enlarged and had hyperechogenic parenchyma. Bile ducts were dilated and hyperechogenic and the gall bladder was dilated. The livers of these animals were enlarged and typical macroscopic and microscopic findings of coccidiosis were present. Treatment with toltrazuril and toltrazuril+ivermectin combination were highly effective in reducing faecal oocyst output in infected rabbits. Haematological, biochemical and lipid peroxidation parameters and, ultrasonographic findings of the liver were close to control values for Groups 3 and 5. Necropsy of these animals showed no visible lesions related to hepatic coccidiosis although a few oocysts were detected in the bile duct epithelial cells.

Pharmacokinetic of sulfisoxazole in aqueous humor after topical and subconjunctival application in dogs.

This study was undertaken to evaluate the ocular pharmacokinetic of sulfisoxazole. Male, 2-3 years old 10 mix breed dogs weighing 12-15 kg were used. A 2 mg dose/eye of sulfisoxazole was administrated to the animals by either subconjunctivally or by topically. Samples of aqueous humor were collected after 0.083, 0.25, 0.5, 1, 2, 4, 6, 24 and 72 h and level of sulfisoxazole was determined. Pharmacokinetic parameters including absorption rate constant (k(a)), slope factor (beta), absorption half-life (t1/2a), half-life of elimination in aqueous humor (t1/2beta), maximal concentration in aqueous humor (C(max)), time to reach C(max) (t(max)), mean residence time in aqueous humor (MRT) and area under the concentration time curve from zero up to infinity (AUC(0-infinity)) were calculated. Compared to topical application, value of k(a) in subconjunctival application increased while values of t1/2a and t(max) decreased and the value of t1/2beta prolonged (p < 0.05). There was no significant difference between groups regarding other parameters (p > 0.05). These results indicate that sulfisoxazole may not be potent enough to treat intraocular infections caused by bacteria when applied either subconjunctivally or topically at a dose of 2 mg/eye. Furthermore, subconjunctival application of sulfisoxazole could be more efficient for treatment of intraocular infections due to higher absorption of drug and longer remaining time in the eye compared to topical application.

Effects of the mycotoxin citrinin on micronucleus formation in a cytokinesis-block genotoxicity assay in cultured human lymphocytes.

Some mycotoxins produced by microfungi are capable of causing disease and death in animals and humans. In the present study, the mycotoxin citrinin (CTN) was evaluated for its genotoxic effects to human peripheral blood lymphocytes from six different individuals. Lymphocyte cultures were treated for 48 h with CTN at six different concentrations between 10 and 100 microM. Lymphocyte cultures were also incubated with 0.1 microM mitomycin c (MMC) as a positive control, and 0.5% absolute ethanol as a vehicle control.CTN caused a significant concentration-dependent increase in micronucleus (MN) frequency in human lymphocytes. At the 60 microM, 80 microM and 100 microM concentrations, CTN was found to induce MN in cytokinesis-blocked lymphocytes in comparison with negative controls (P = 0.014). All the CTN concentrations also led to a clear decrease in the percentages of binucleated/mononucleated cells (P = 0.014). These results indicate that CTN at high concentrations is genotoxic in cultured human lymphocytes.

Effects of ochratoxin A on micronucleus frequency in human lymphocytes.

Ochratoxin A (OTA), a nephrotoxic and carcinogenic mycotoxin, was investigated to examine its potency to induce micronuclei (MN) in cultured human lymphocytes. Lymphocyte cultures were treated for the last 48 h with OTA at concentrations of 25 microM, 10 microM, 1 microM, 100 nM, 10 nM, 1 nM, and 100 microM and absolute ethanol. At the highest concentration, OTA was found to induce MN in cytokinesis-blocked lymphocytes (p < 0.05). The 25 microM OTA concentration also led to a clear decrease in the percentage of binucleated cells, probably due to cytotoxicity. OTA at the other concentrations tested did not induce MN frequency. These results indicate that a high concentration of OTA is genotoxic in cultured human lymphocytes.