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

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

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