Hepatoprotective and renoprotective effects of silymarin against salinomycin-induced toxicity in adult rabbits.

Background and Aim: Salinomycin sodium, a licensed coccidiostat in rabbits, is used for fattening at a dose of 20-25 mg/kg. Salinomycin toxicity may arise from many risk factors (e.g., overdosage or use in non-target animal species). Silymarin extracted from milk thistle has antioxidant, anti-inflammatory, and antiviral properties. This study aimed to investigate the adverse impacts of oral administration of salinomycin for 28 consecutive days and how to reduce its risks and side effects by administering silymarin. Materials and Methods: Eighty-four male New Zealand White bucks (1.750-2.000 kg) were randomly divided into seven groups (12 each). Group one was the control. Groups two and three were administered salinomycin orally (doses of 20 and 40 mg/kg ration). Group four was administered salinomycin (20 mg/kg ration) and silymarin (6.5 mg/kg body weight [BW]). Group five received salinomycin (40 mg/kg ration) and silymarin (13 mg/kg BW). Groups six and seven were administered silymarin at doses of 6.5 and 13 mg/kg BW. Rabbits were euthanized and slaughtered on day 29 using the Halal method. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, urea, total proteins, albumin, total cholesterol, and high- and low-density lipoprotein (HDL and LDL) were analyzed in serum. Glutathione (GSH), superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) were estimated in the liver. A histopathological investigation was performed on the liver and kidney. Results: The MDA activity, AST, ALT, total protein, albumin, total cholesterol, triglyceride, LDL, urea, and creatinine values were significantly elevated in groups two and three. The GSH, catalase, SOD, and HDL were significantly lower in these groups than in the control group. There were moderate pathologic changes in the liver and kidney of the third group. However, the results of the fourth and fifth groups improved more than those of the second and third groups. The results of the sixth and seventh groups were nearly the same as those of the control group. Conclusion: Salinomycin toxicity was caused by oxidative damage because of reactive oxygen species formation. Silymarin (6.5 or 13 mg/kg BW) tends to prevent and treat accidental toxicity. However, the high dose of silymarin (13 mg/kg BW) had more renal and hepatoprotective capacities.

Effects of several organophosphates on hepatic cytochrome P450 activities in rats.

Four commonly used organophosphates (fenitrothion, dichlorvos, chlorpyrifos, and trichlorfon) were orally administered to male Sprague-Dawley rats for five days in order to explore their effects on the activities of liver cytochrome P450 (CYP). In addition, Michaelis-Menten kinetics of the metabolic reactions catalyzed by liver CYPs were analyzed following the addition of these compounds to the assay system to examine their potential inhibitory effects on liver CYPs activities. These reactions included ethoxyresorufin O-deethylation, midazolam 4-hydroxylation, tolbutamide hydroxylation, and bufuralol 1'-hydroxylation for CYP1A, 3A, 2C, and 2D activities, respectively. Total CYP content was also examined after oral administration of each organophosphate. Results revealed that oral giving of fenitrothion inhibited significantly CYP1A and 3A activities while elevated activity of CYP2C. Fenitrothion is a potent inhibitor for CYP1A and 2C with Ki values of 0.42 and 36.1 µM, respectively but had a weak inhibitory effect on CYP2D and 3A with Ki values of 290 and 226 µM, respectively. Chlorpyrifos is a potent inhibitor of CYP1A with Ki 0.24 µM and moderately inhibited CYP2C or 3A with Ki values of 84.8 and 77.7 µM, respectively. On the other hand, dichlorvos and trichlorfon caused extremely low or negligible inhibition of different CYP activities. From these results, it is concluded that both fenitrothion and chlorpyrifos may increase the toxicity of chemicals in environmental living organisms through their potent inhibitory effects on these CYP activities, but dichlorvos and trichlorfon may not.

Subacute Toxicity of Nerium oleander Ethanolic Extract in Mice.

Nerium oleander (N. oleander) is a well-known poisonous shrub that is frequently grown in gardens and public areas and contains numerous toxic compounds. The major toxic components are the cardiac glycosides oleandrin and neriin. The aim of our study was to evaluate the toxic effects of an ethanolic N. oleander leaf extract on haematological, cardiac, inflammatory, and serum biochemical parameters, as well as histopathological changes in the heart. N. oleander extract was orally administered for 14 and 30 consecutive days at doses of 100 and 200 mg of dried extract/kg of body weight in 0.5 mL of saline. The results showed significant increases in mean corpuscular volume, white blood cell counts, platelet counts, interleukins (IL-1 and IL-6), tumour necrosis factor alpha, C reactive protein, alanine aminotransferase, lactate dehydrogenase, creatine kinase and creatine kinase MB, especially at high doses. Marked pathological changes were perceived in the heart tissue. Thus, it can be concluded that exposure to N. oleander leaf extract adversely affects the heart and liver.

Ceftiofur pharmacokinetics in Nile tilapia Oreochromis niloticus after intracardiac and intramuscular administrations.

Ceftiofur is a broad-spectrum third generation cephalosporin, which acts by inhibiting bacterial cell wall synthesis. It is active against Gram-positive and Gram-negative bacteria such as Aeromonas hydrophila and ß-lactamase-producing strains, which are common pathogens in freshwater fish. Ceftiofur pharmacokinetics in Nile tilapia Oreochromis niloticus were studied following single intracardiac (i.c.) or intramuscular (i.m.) administration of ceftiofur sodium (NAXCEL®) in a dose of 5 mg ceftiofur kg-1 body weight. After i.c. injection, ceftiofur plasma concentrations decreased biexponentially, suggesting a 2-compartmental open model. Distribution and elimination half-lives (t0.5(α) and t0.5(ß)) were 0.61 ± 0.22 and 0.14 ± 0.03 h mean ±SD, respectively. Elimination constant (Kel) and total body clearances (Cltot) were 3.22 ± 0.48 h-1 and 1.64 ± 0.47 l h-1 kg-1, respectively. Volume of distribution (Vss) and areas under curves (AUC) were 0.12 ± 0.03 l kg-1 and 24.18 ± 8.81 µg ml-1 h, respectively. Following i.m. injection of ceftiofur, plasma concentrations were best described by a 1-compartment open model with a first order absorption; bioavailability was quite high (96.85 ± 23.74%). Plasma maximum concentration (Cmax) was 12.32 ± 6.53 µg ml-1; achieved at time of maximum concentration (Tmax) of 0.74 ± 0.04 h. Absorption and elimination half-lives (t0.5ab and t0.5ß) were 0.49 ± 0.06 and 0.53 ± 0.03 h, respectively. In conclusion, i.m. injection of ceftiofur sodium produced extremely high bioavailability with high plasma concentrations that persisted up to 6 h post injection, which may make ceftiofur a useful alternative antibiotic for treatment of brood stock or important ornamental fishes.

Protective Effects of Diallyl Sulfide and Curcumin Separately against Thallium-Induced Toxicity in Rats.

Thallium acetate (TI) is a cumulative poison intimately accompanied by an increase in reactive oxygen species (ROS) formation that represents an important risk factor for tissue injury and malfunction. This study aims to determine the possible hepatoprotective and antioxidant effects of diallyl sulfide (DAS) from garlic and curcumin from turmeric against TI-induced liver injury and oxidative stress (OS) in rats. This in vivo animal study divided rats into six groups of 8 rats per group. The first group received saline and served as the control group. The second and third groups received DAS or curcumin only at a dose of 200 mg/kg. The fourth group received TI at a dose of 6.4 mg/kg for 5 consecutive days. The fifth and sixth groups received DAS or curcumin orally 1 hour before TI intoxication at the same dose as the second and third groups. Liver integrity serum enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and γ-glutamyltransferase (γ-GT) were evaluated. Serum and liver tissue homogenate lipid peroxidation and OS biomarkers were measured. The data were analyzed by one-way ANOVA followed by Duncan's multiple range test for post hoc analysis using SPSS version 16. TI induced marked oxidative liver damage as shown by significantly (P≤0.05) elevated serum AST, ALT, ALP, LDH and γ-GT levels. There were significant (P≤0.05) increases in serum and hepatic malondialdehyde (MDA) and serum nitric oxide (NO) as well as decreased hepatic glutathione (GSH) and catalase (CAT) activities. There were significantly (P≤0.05) less serum and hepatic superoxide dismutase (SOD) and total antioxidant capacity (TAC). Pre-treatment with DAS or curcumin ameliorated the changes in most studied biochemical parameters. DAS and curcumin effectively reduced TI-induced liver toxicity.

Toxicological and biochemical studies on Schinus terebinthifolius concerning its curative and hepatoprotective effects against carbon tetrachloride-induced liver injury.

BACKGROUND: Recently, many efforts have been made to discover new products of natural origin which can limit the xenobiotic-induced hepatic injury. Carbon tetrachloride (CCl4) is a highly toxic chemical that is widely used to study hepatotoxicity in animal models. OBJECTIVE: The present study was conducted to investigate the curative and protective effects of Schinus terbenthifolius ethanolic extract against CCl4 -induced acute hepatotoxicity in rats. MATERIALS AND METHODS: S. terbenthifolius extract was orally administered in a dose of 350 mg dried extract/kg b.wt. before and after intoxication with CCl4 for curative and protective experiments, respectively. A group of hepatotoxicity indicative enzymes, oxidant-antioxidant capacity, DNA oxidation, and apoptosis markers were measured. RESULTS: CCl4 increased liver enzyme leakage, oxidative stress, hepatic apoptosis, DNA oxidation, and inflammatory markers. Administration of S. terebinthifolius, either before or after CCl4 intoxication, significantly decreased elevated serum liver enzymes and reinstated the antioxidant capacity. Interestingly, S. terebinthifolius extract inhibited hepatocyte apoptosis as revealed by approximately 20 times down-regulation in caspase-3 expression when compared to CCl4 untreated group. On the other hand, there was neither protective nor curative effect of S. terebinthifolius against DNA damage caused by CCl4. CONCLUSION: The present study suggests that S. terebinthifolius extract could be a substantially promising hepatoprotective agent against CCl4 toxic effects and may be against other hepatotoxic chemical or drugs.

Alpha-lipoic acid improves acute deltamethrin-induced toxicity in rats.

Alpha-lipoic acid (ALA) is a natural dithiol compound, with a free radical scavenger and biological antioxidant properties. The purpose of the current study was to investigate the protective effects of ALA on biochemical alteration and oxidative stress induced by acute deltamethrin intoxication in rats. Markers of liver and kidney injuries in serum of deltamethrin-intoxicated as well as ALA-pretreated rats were analyzed. Moreover, serum and (or) tissue lipid peroxidation, malondialdehyde and antioxidant markers, reduced glutathione, catalase, superoxide dismutase activity, and total antioxidant capacity were evaluated. The results showed that all parameters were altered in the intoxicated group, indicating hepatorenal oxidative damage of deltamethrin. Pre-treatment with ALA reversed the changes in most of the studied parameters in a dose-dependent manner. Histopathological and biochemical findings were parallel. It can be concluded that ALA may be a promising therapeutic option for prevention and (or) treatment of deltamethin toxicity.