Treatment and protective effects of metalloproteinase inhibitors alone and in combination with N-Acetyl cysteine plus vitamin E in rats exposed to aflatoxin B1.

This study was conducted to investigate the effects of matrix metalloproteinase (MMP) inhibitors dexamethasone and minocycline administrations -both single and in combination with N-acetylcysteine (NAC) and vitamin E-on the tissue distribution and lethal dose (LD)50 of aflatoxin (AF)B1 in rats. We performed this study on male Wistar rats (8-10 weeks) in two phases. In the first phase, rats were administered dexamethasone (5 and 20 mg/kg) and minocycline (45 and 90 mg/kg), both as single treatments and in combination with NAC (200 mg/kg) and vitamin E (600 mg/kg); these treatments followed AFB1 administration (2 mg/kg). In the second phase, the therapeutic effect value (TEV) was calculated to determine the treatment effect on the LD50 level of AFB1. The tissue affinity of AFB1 from high to low was liver, kidney, intestine, brain, heart, spleen, lung, testis, and vitreous humor, respectively. Dexamethasone at the 20 mg/kg dose significantly reduced AFB1 concentrations in the plasma and the other tissues, except for the vitreous humor. The effects of minocycline on the plasma and tissue concentrations of AFB1 varied by dose and tissue. The combinations of dexamethasone or minocycline with NAC and vitamin E increased the AFB1 concentrations in the plasma and all tissues, except for vitreous humor and liver. In male rats, the LD50 value of AFB1 was 11.86 mg/kg. The TEV of dexamethasone (20 mg/kg) was calculated to be 1.5. Dexamethasone can be administered in repeated doses at ≥20 mg/kg to increase survival in AFB1 poisoning.

Alpha lipoic acid and vitamin E improve atorvastatin-induced mitochondrial dysfunctions in rats.

To determine the effects of alpha lipoic acid (ALA) and vitamin E (Vit E) on mitochondrial dysfunction caused by statins. A total of 38 Wistar Albino rats were used in this study. The control group received dimethyl sulfoxide. The atorvastatin (A) group received atorvastatin (10 mg/kg). The A + ALA group received atorvastatin (10 mg/kg) and ALA (100 mg/kg). The A + Vit E group was administered atorvastatin (10 mg/kg) and Vit E (100 mg/kg). The A + ALA + Vit E group was administered atorvastatin (10 mg/kg), ALA (100 mg/kg) and Vit E (100 mg/kg). All applications were administered simultaneously by gavage for 20 days. ATP level and complex I activity were measured from liver, muscle, heart, kidney and brain. Atorvastatin significantly decreased the ATP levels in heart and kidney, while a slight decrease was seen in liver, muscle and brain. Atorvastatin caused an insignificant decrease in the complex I activity in all tissues examined. ALA administration significantly improved the ATP levels in the liver, heart and kidney, while Vit E improved the ATP levels in all tissues except the muscle compared to Atorvastatin group. Single administration of both ALA and vit E ameliorated complex I activity in the muscle, heart, kidney and brain. The combination of ALA and Vit E significantly improved the ATP levels in the liver, heart, kidney and brain and also provided significant improvements the complex I activity in all tissues. The undesirable effects of Atorvastatin on mitochondrial functions in this study ameliorated by using ALA and/or Vit E alone and in combination.

Investigation of pharmacokinetic interaction between ivermectin and praziquantel after oral administration in healthy dogs.

The purpose of this study was to determine the pharmacokinetic interaction between ivermectin (0.4 mg/kg) and praziquantel (10 mg/kg) administered either alone or co-administered to dogs after oral treatment. Twelve healthy cross-bred dogs (weighing 18-21 kg, aged 1-3 years) were allocated randomly into two groups of six dogs (four females, two males) each. In first group, the tablet forms of praziquantel and ivermectin were administered using a crossover design with a 15-day washout period, respectively. Second group received tablet form of ivermectin plus praziquantel. The plasma concentrations of ivermectin and praziquantel were determined by high-performance liquid chromatography using a fluorescence and ultraviolet detector, respectively. The pharmacokinetic parameters of ivermectin following oral alone-administration were as follows: elimination half-life (t1/2λz ) 110 ± 11.06 hr, area under the plasma concentration-time curve (AUC0-∞ ) 7,805 ± 1,768 hr. ng/ml, maximum concentration (Cmax ) 137 ± 48.09 ng/ml, and time to reach Cmax (Tmax ) 14.0 ± 4.90 hr. The pharmacokinetic parameters of praziquantel following oral alone-administration were as follows: t1/2λz 7.39 ± 3.86 hr, AUC0-∞ 4,301 ± 1,253 hr. ng/ml, Cmax 897 ± 245 ng/ml, and Tmax 5.33 ± 0.82 hr. The pharmacokinetics of ivermectin and praziquantel were not changed, except Tmax of praziquantel in the combined group. In conclusion, the combined formulation of ivermectin and praziquantel can be preferred in the treatment and prevention of diseases caused by susceptible parasites in dogs because no pharmacokinetic interaction was determined between them.

Effects of enrofloxacin, flunixin meglumine and dexamethasone on disseminated intravascular coagulation, cytokine levels and adenosine deaminase activity in endotoxaemia in rats.

The aim of this study was to determine the effects of drugs used in the treatment of endotoxaemia on disseminated intravascular coagulation, cytokine levels and adenosine deaminase activities in endotoxaemic rats. Rats were divided into seven groups. Lipopolysaccharide (LPS) was injected into all groups, including the positive control group. The other six groups received the following drugs: enrofloxacin (ENR), flunixin meglumine (FM), low-dose dexamethasone (DEX), high-dose DEX, ENR + FM + low-dose DEX, and ENR + FM + high-dose DEX. After the treatments, serum and plasma samples were collected at 0, 1, 2, 4, 6, 8, 12, 24 and 48 hours (h). A coagulometer was used to determine the levels of coagulation values, while ELISA was used to assay serum cytokines and adenosine deaminase (ADA). Low-dose DEX alone and combined treatments depressed the levels of cytokines and ADA (from 371 to 70 IU/L at 6 h) significantly and inhibited the decrease of coagulation values (antithrombin from 67 to 140% at 6 h, fibrinogen from 54 to 252 mg/dL at 6 h). In summary, FM + high-dose DEX may be the preferred treatment of endotoxaemia because of its highest effectiveness. FM plus high-dose DEX may be a new therapy for endotoxaemic domestic animals.