L-karnitin ublažava hepatotoksičnost bisfenola A aktiviranjem Nrf2 i inhibicijom proupalne ekspresije gena citokina u štakora

Bisphenol, used in many polycarbonate plastics and epoxy resins industries, exerts toxic effects on mammalian organs. The mechanisms underlying bisphenol toxicity are well understood, however the chemoprevention effects of L-carnitine have not yet been recorded. This study aimed to explore the protective mechanism of L-carnitine against BPA-induced hepatotoxicity. Male rats were randomly distributed into 4 groups of 10 rats each: vehicle (5 mL corn oil/kg), bisphenol (50 mg/kg b.w. orally), L-carnitine (500 mg/kg b.w. i/p), and L-carnitine bisphenol pre-treated groups. Bisphenol was dissolved in corn oil and gavaged for 70 consecutive days. Up-regulation of tumor necrosis factor (6.6-fold), and interleukin 6 (3.2-fold) mRNA transcript, along with suppression of nuclear factor erythroid 2-like 2 (0.4-fold), were recorded, following bisphenol administration. Subsequently, bisphenol provoked oxidative stress and attenuated the antioxidative molecules. Finally, hepatic dysfunction was assessed by elevated serum aminotransferases, alkaline phosphatase, lactate dehydrogenase, glutamyl transferase activities and ammonia levels, with the subsequent decline in serum albumin concentration, which confirmed the inflammatory cell infiltration and hydropic degeneration, and the impairment of lipid profile. Interestingly, co-administration of L-carnitine improved liver function and lipid profile, which was explained by the activation of nuclear factor erythroid 2-like 2 (1.5-fold) mRNA transcript, which augmented the antioxidant levels and suppressed oxidative stress, tumor necrosis factor (2.6- fold), and interleukin 6 (1.5-fold) gene expression. In conclusion, L-carnitine exerted hepatoprotective activity against bisphenol toxicity via antioxidant and anti-inflammatory effects.Bisfenol, koji se koristi u mnogim industrijama polikarbonatne plastike i epoksidnih smola, ima toksične učinke na organe sisavaca. Mehanizmi na kojima se temelji toksičnost bisfenola dobro su razumljivi, međutim učinci L-karnitina na kemoprevenciju još nisu zabilježeni. Cilj ovog ispitivanja bio je istražiti zaštitni mehanizam L-karnitina protiv hepatotoksičnosti izazvane BPA-om. Mužjaci štakora slučajnim su odabirom podijeljeni u su u 4 skupine od po 10 štakora: kontrolna skupina (5 mL kukuruznog ulja/kg tjelesne težine), duga skupina (50 mg bisfenol/kg tjelesne težine peroralno), teća skupina (500 mg L-karnitin/kg tjelesne težine i/p) i četvrta skupina (L-karnitin apliciran skupini prethodno tretiranoj bisfenolom). Bisfenol je otopljen u kukuruznom ulju kojim su štakori hranjeni 70 uzastopnih dana. Nakon primjene bisfenola zabilježeno je povećanje mRNK transkripta za stvarnje faktora tumorske nekroze i interleukina 6 uz supresiju nukleotidnog faktora sličnog eritroidu 2, povezanog s faktorom 2. Nakon toga bisfenol je izazvao oksidativni stres i oslabio antioksidativne molekule. Naposljetku, disfunkcija jetre procjenjivana je povišenim razinama aminotransferaza u serumu, alkalne fosfataze, laktat dehidrogenaze, aktivnosti glutamiltransferaze i amonijaka, uz naknadno smanjenje koncentracije serumskog albumina, što je potvrdilo infiltraciju upalnih stanica i hidropičnu degeneraciju, te narušavanje lipidnog statusa. Zanimljivo je da je istodobna primjena L-karnitina poboljšala funkciju jetre i lipidni status, što je objašnjeno aktivacijom transkripta mRNK tipa 2 povezanog s faktorom 2, koji je povećao razine antioksidansa i potisnuo oksidativni stres, te ekspresiju gena faktora tumorske nekroze i interleukina 6. Zaključno, L-karnitin je pokazao hepatozaštitnu aktivnost protiv toksičnosti bisfenola antioksidativnim i protuupalnim učincima

Evaluation of acute toxicity of genabilic acid (menbutone 10%) in rabbits

[EN] A complete investigation of the acute toxicity of a choleretic compound, menbutone, was performed in rabbits, including lethal dose for 50% of rabbits determination, clinical signs observation and in vivo and post-mortem examinations. Haematological, biochemical and histopathological changes resulting from intramuscular injection of menbutone were also investigated at dose 400 mg/kg body weight. Acute toxicity of menbutone at dose of 400 mg/kg BW induced interstitial myocarditis and multifocal necrosis, whereas serum creatine phosphokinase, creatinine phosphokinase-MB isoenzyme and aspartate aminotransferase activities were significantly increased. Elevation of serum alanine aminotransferase and alkaline phosphatase activities and total bilirubin level associated with lowered albumin content was consistent with histopathological changes of hepatic tissues; hepatic necrosis and fatty infiltration were pronounced indicators of injuries. Renal tubular necrosis and interstitial nephritis were also observed in intoxicated rabbits. Menbutone also induced variations in some haematological parameters. We concluded that acute toxicity of menbutone in rabbits occurred at accidental high doses, as the lethal dose was about 50 fold over the recommended therapeutic dose for other animals. Cardiac muscle, liver and kidneys are the main target organs for menbutone toxicity. Menbutone is not recommended for use in rabbits suffering from any cardiacand hepatic disorders, especially in overdosing situations.El Okle, SO.; Tohamy, GH.; Lebda, AM. (2014). Evaluation of acute toxicity of genabilic acid (menbutone 10%) in rabbits. World Rabbit Science. 22(3):215-222. doi:10.4995/wrs.2014.1791.SWORD215222223Cardinale, D., Sandri, M. T., Colombo, A., Colombo, N., Boeri, M., Lamantia, G., … Cipolla, C. M. (2004). Prognostic Value of Troponin I in Cardiac Risk Stratification of Cancer Patients Undergoing High-Dose Chemotherapy. Circulation, 109(22), 2749-2754. doi:10.1161/01.cir.0000130926.51766.ccCulling C.F. 1983. Handbook of Histopathological and Histochemical Techniques, 3rd ed. London, Boston: Butterworth.De la Cruz-Hernández N.I., Argudín-Salomón O.A., Zertuche- Rodríguez J.L., Medellín-Ledezma J.A., Flores-Gutiérrez G.H. 2012. Case report: outbreak of sodium monensin intoxication in feedlot cattle from Mexico. Revue Med. Vet., 163: 60-63.Pershin G.N. 1971. Methods of experimental chemotherapy: Practical guidance, 2nd edition, Moscow. Russia: Medicina

Commiphora myrrh Supplementation Protects and Cures Ethanol-Induced Oxidative Alterations of Gastric Ulceration in Rats

Gastric ulceration is a multifactorial disease defined as a defect in the gastric wall that extends through the muscularis mucosae into the deeper layers of the wall. The most common cause of gastric ulceration is alcohol consumption. In the current study, rats were gavaged by ethanol to investigate the protective (before ethanol) and curative (after ethanol) ability of Commiphora myrrh (myrrh) oil and extract against gastric ulcer oxidative alterations induced by ethanol. Myrrh significantly improved ulcer index, histomorphology, and periodic acid Schiff (PAS) impaired by ethanol. In addition, myrrh improved the antioxidant potential of gastric mucosa through enhancement of nuclear factor related to erythroid 2 (Nrf2), total glutathione (GSH), reduced GSH, and oxidized glutathione (GSSG), along with significant reduction in malondialdehyde (MDA) levels. Amelioration of gastric oxidative stress by myrrh enables gastric mucosa to counteract the ethanol’s inflammatory and apoptotic processes leading to improved gastric proliferation and healing. Interestingly, myrrh extract showed better protective and curative effects than myrrh oil against gastric ulceration

Effects of ginger extract and/or propolis extract on immune system parameters of vaccinated broilers

ABSTRACT: Newcastle disease (ND), avian influenza (AI, H5N8), and infectious bronchitis (IB) are important diseases in the poultry industry and cause significant losses. Vaccination is the most practical method for controlling infectious diseases. To reduce vaccination costs and several disorders in poultry farms, using herbal water supplements for immunomodulation with vaccination is critical to improving or preventing some conditions in the poultry industry. However, drinking water supplementation of ginger extract (GE)/propolis extract (PE) alone/in combination may increase broilers’ humoral and cellular immunity due to the immunomodulatory effects of ginger and propolis. This protocol aimed to see how GE/PE alone or in combination improved the immunity, immune organ gene expression, and histology of the immune organs of broilers for 35 d after vaccination against NDV, H5N8, IBV, and IBDV. The chicks were dispensed into 5 groups according to GE and/or PE with vaccination. The control group was offered normal drinking water without any supplements or vaccinations. The GE group was supplemented with ginger extract (1 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The GE+PE group was supplemented with GE (0.5 mL/L drinking water) and PE (0.5 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The PE group was supplemented with propolis extract (1 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The fifth group was the vaccinated untreated group. This experiment showed the immunomodulatory properties of GE and/or PE against 3 common diseases, NDV, AI, and IB, in broiler chicken farms for 35 d applied to a vaccination program. Thus, ginger extract and propolis extract supplementation in drinking water increased antibody titer, INF, IL10, and IL2 and TLR3 gene expression in the bursa of Fabricius, thymus, and spleen, respectively, as well as cellular immunity as indicated by increased CD3, CD4, and CD8 in the bursa of Fabricius, thymus, and spleen, respectively, with normal lymphocytes in the medulla of the bursa, thymus, and spleen. In conclusion, propolis extracts alone or with GE improved all of the metrics mentioned above without harming the histology of the immune organs

Quercetin Attenuates Brain Oxidative Alterations Induced by Iron Oxide Nanoparticles in Rats

Iron oxide nanoparticle (IONP) therapy has diverse health benefits but high doses or prolonged therapy might induce oxidative cellular injuries especially in the brain. Therefore, we conducted the current study to investigate the protective role of quercetin supplementation against the oxidative alterations induced in the brains of rats due to IONPs. Forty adult male albino rats were allocated into equal five groups; the control received a normal basal diet, the IONP group was intraperitoneally injected with IONPs of 50 mg/kg body weight (B.W.) and quercetin-treated groups had IONPs + Q25, IONPs + Q50 and IONPs + Q100 that were orally supplanted with quercetin by doses of 25, 50 and 100 mg quercetin/kg B.W. daily, respectively, administrated with the same dose of IONPs for 30 days. IONPs induced significant increases in malondialdehyde (MDA) and significantly decreased reduced glutathione (GSH) and oxidized glutathione (GSSG). Consequently, IONPs significantly induced severe brain tissue injuries due to the iron deposition leading to oxidative alterations with significant increases in brain creatine phosphokinase (CPK) and acetylcholinesterase (AChE). Furthermore, IONPs induced significant reductions in brain epinephrine, serotonin and melatonin with the downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (mtTFA) mRNA expressions. IONPs induced apoptosis in the brain monitored by increases in caspase 3 and decreases in B-cell lymphoma 2 (Bcl2) expression levels. Quercetin supplementation notably defeated brain oxidative damages and in a dose-dependent manner. Therefore, quercetin supplementation during IONPs is highly recommended to gain the benefits of IONPs with fewer health hazards