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

Pattern of Congenital Anomalies in Newborn: A Hospital-Based Study

Birth defects, encountered frequently by pediatricians, are important causes of childhood morbidity and mortality. Birth defects can be classified according to their severity, pathogenic mechanism, or whether they are involving a single system or multiple systems. This hospital-based prospective descriptive study highlights the prevalence of Congenital Anomalies (CAs) in one year among live born neonates delivered in Zagazig University Hospital (Egypt). All women giving birth to viable babies were included. Demographic details, associated risk factors and the type of CAs in all babies were recorded. Diagnosis of CAs was based on clinical evaluation, radiographic examination, ultrasonography, echocardiography and chromosomal analysis of the newborn whenever recommended. The overall incidence of CAs among live born neonates was 2.5%, as most of the cases were referred to Zagazig University Hospital (Egypt) for delivery. The musculoskeletal system (23%) was the most commonly involved followed by the central nervous system (20.3%). Involvement of more than one system was observed in (28.6%) cases. Among maternal and fetal risk factors; parental consanguinity, maternal under nutrition and obesity, positive history of an anomaly in the family, low birth weight, and prematurity were significantly associated with higher frequency of CAs (P<0.05), with non-significant differences for maternal age and the sex of the neonates. The current study highlights the prevalence of congenital anomalies in one year in Zagazig University Hospital. It revealed a high prevalence of congenital anomalies in our locality and stressed the importance of carrying out a thorough clinical examination of all neonates at birth

Chicory (Cichorium intybus L.) root extract regulates the oxidative status and antioxidant gene transcripts in CCl4-induced hepatotoxicity.

The ability of Cichorium intybus root extract (chicory extract) to protect against carbon tetrachloride (CCl4)-induced oxidative stress and hepatotoxicity was evaluated in male rats. The rats were divided into four groups according to treatment: saline (control); chicory extract (100 mg/kg body weight daily, given orally for 2 weeks); CCl4 (1 ml/kg body weight by intraperitoneal injection for 2 consecutive days only); or chicory extract (100 mg/kg body weight daily for 2 weeks) + CCl4 injection on days 16 and 17. The levels of hepatic lipid peroxidation, antioxidants, and molecular biomarkers were estimated twenty-four hours after the last CCl4 injection. Pretreatment with chicory extract significantly reduced CCl4-induced elevation of malondialdehyde levels and nearly normalized levels of glutathione and activity of glutathione S-transferase, glutathione peroxidase (GPx), glutathione reductase, catalase (CAT), paraoxonase-1 (PON1), and arylesterase in the liver. Chicory extract also attenuated CCl4-induced downregulation of hepatic mRNA expression levels of GPx1, CAT and PON1 genes. Results of DNA fragmentation support the ability of chicory extract to ameliorate CCl4-induced liver toxicity. Taken together, our results demonstrate that chicory extract is rich in natural antioxidants and able to attenuate CCl4-induced hepatocellular injury, likely by scavenging reactive free radicals, boosting the endogenous antioxidant defense system, and overexpressing genes encoding antioxidant enzymes

Quercetin Attenuates Pancreatic and Renal D-Galactose-Induced Aging-Related Oxidative Alterations in Rats

Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (p53, p21, IL-6, and IL-8), apoptotic (Bax, CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic (Bcl2 and Bcl2 protein), inflammatory (NF-κB, IL-1β, and TNF-α), antioxidant (SOD1), and functional markers (GCLC and GCLM genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health

Effect of aqueous extract of chicory root on the lipid peroxidation biomarker malondialdehyde and antioxidant molecules in the liver homogenates of rats exposed to carbon tetrachloride.

<p>^{(<i>a</i>, <i>b</i>, <i>c</i>)} Different superscript letters within a column indicate significantly different mean values (<i>p</i> < 0.05). CCl₄, carbon tetrachloride; CE, chicory extract; MDA, malondialdehyde; GSH, reduced glutathione; GST, glutathione S-transferase; GPx, glutathione peroxidase; GR, glutathione reductase; CAT, catalase; PON1, paraoxonase 1; AE, arylesterase.</p><p>Effect of aqueous extract of chicory root on the lipid peroxidation biomarker malondialdehyde and antioxidant molecules in the liver homogenates of rats exposed to carbon tetrachloride.</p

Agarose gel electrophoresis of extracted DNA from liver of rats.

<p>Results of the DNA fragmentation assay confirm that pretreatment with chicory extract attenuates CCl4-induced hepatotoxicity in rats. Lane M, DNA ladder; Lanes 1–2, untreated control group; Lanes 3–4, chicory extract-treated group; Lanes 5–9, CCl4-treated group, and Lane 10, chicory extract+CCl4-treated group.</p

Effect of aqueous extract of chicory root on mRNA expression levels of antioxidant enzyme genes <i>GPx1</i>, <i>CAT</i>, and <i>PON1</i> in the liver of rats exposed to carbon tetrachloride.

<p>^{(<i>a</i>, <i>b</i>, <i>c</i>, <i>d</i>)} Different superscript letters within a column indicate significantly different mean values (<i>p</i> < 0.05). CCl_4, carbon tetrachloride; CE, chicory extract; <i>GPx</i>1, glutathione peroxidase 1; <i>CAT</i>, catalase; <i>PON</i>1, paraoxonase 1.</p><p>Effect of aqueous extract of chicory root on mRNA expression levels of antioxidant enzyme genes <i>GPx1</i>, <i>CAT</i>, and <i>PON1</i> in the liver of rats exposed to carbon tetrachloride.</p

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