Valproate is known to disturb the kidney function, and high doses or prolonged intake may cause serum ion imbalance, kidney tubular acidosis, proteinuria, hyperuricosuria, polyuria, polydipsia, and ...dehydration. The aim of this
study was to see whether naringin would counter the adverse effects of high-dose valproate in C57Bl/6 mice and to which extent. As expected, valproate (150 mg/kg bw a day for 10 days) caused serum hyperkalaemia, more in male than female mice. Naringin reversed (25 mg/kg bw a day for 10 days) the hyperkalaemia and activated antioxidative defence mechanisms (mainly catalase and glutathione), again more efficiently in females. In males naringin combined with valproate was not as effective and even showed some prooxidative effects.
Valproate is a common antiepileptic drug whose adverse effects include liver steatosis and dyslipidaemia. The aim of our study was to see how natural flavonoid antioxidant naringin would interact ...with valproate and attenuate these adverse effects. For this reason we treated male C57BL6 mice with a combination of 150 mg/kg of valproate and 25 mg/kg naringin every day for 10 days and compared their serum triglycerides, cholesterol, LDL, HDL, VLDL, and liver PPAR-alpha, PGC-1 alpha, ACOX1, Nrf2, SOD, CAT, GSH, and histological signs of steatosis. Valproate increased lipid peroxidation parameters and caused pronounced microvesicular steatosis throughout the hepatic lobule in all acinar zones, but naringin co-administration limited steatosis to the lobule periphery. In addition, it nearly restored total serum cholesterol, LDL, and triglycerides and liver ACOX1 and MDA to control levels. and upregulated PPAR-alpha and PGC-1 alpha, otherwise severely downregulated by valproate. It also increased SOD activity. All these findings suggest that naringin modulates key lipid metabolism regulators and should further be investigated in this model, either alone or combined with other lipid regulating drugs or molecules.
Valproic acid (VPA) is a short fatty acid with strong anticonvulsant properties. It has diverse effects in different tissues with opposing mechanisms of physiological action. Due to the effects on ...energy, fatty acid, and cholesterol metabolism, it may be a risk factor for the development of diabetes with its associated complications of atherosclerosis, weight gain, hypertension, insulin resistance and other complications. Its negative effects on the endocrine system can have severe health consequences, especially in the female population.VPA produces proinflammatory and proapoptotic effects in the liver and anti-inflammatory and antiapoptotic effects in the central nervous system. It also causes abnormalities in lipid and cholesterol transport in the liver and the reproductive organs, while in neural stem cells it decreases cholesterol accumulation and helps neural growth and differentiation. However, in the CNS it has some beneficial effects which are proposed to be important in Alzheimer’s disease (AD). In AD mouse models, VPA exerted antiapoptotic effects and the expression of transcription factors that promote neurite growth. Most of the adverse pathogenic actions or beneficial molecular effects are not fully understood. We present an overview and comparison of the different properties of VPA and their effects on estrogen and cholesterol metabolism, lipid transport, Alzheimer’s disease, and on the physiology of the liver, reproductive organs, and neuronsfrom in vitro and in vivo (in animal models and patients) studies.
Obesity, a major health problem worldwide, is associated with increased cardiovascular risk factors, such as dyslipidemia, glucose intolerance, and hypertension. We investigated the antioxidative ...capacity of the ethanol extract of propolis (EEP) and its effect on the lipid profile, the hepatorenal function, and the atherogenic indices in mice fed with a high-fat diet (HFD). EEP (50 mg/kg) was given orally to mice for 30 days. After the treatments, levels of the serum total triglyceride and cholesterol, the high density lipoprotein (HDL-c) and low density lipoprotein (LDL-c) cholesterols, the serum enzymes, and the metabolites were measured, and atherogenic indices atherogenic index of plasma (AIP); cardiac risk ratio (CRR); cardioprotective index (CPI); atherogenic coefficient (AC) were calculated and compared with the antioxidant, the reducing power, the radical-scavenging, and the chelating activity of EEP. The HFD diet with EEP significantly reduced the negative lipid profile and lowered AIP, CRR, and AC and increased CPI in animals on a HFD. In addition, EEP reduced the weight of mice and lipid accumulation in the liver, and it had significant in vitro antioxidative activities. The EEP possesses anti-hyperlipidemic and antioxidant activity and exhibits protective action on the cardiovascular system and hepatorenal functions. Our results contribute towards the validation of the traditional use of propolis as a food supplement in aiding hyperlipidemic disorders.
Valproat je najčešće korišten antiepileptik, čiji štetni učinci uključuju masnu jetru (steatozu) i dislipidemiju. Cilj istraživanja bio je utvrditi kako će prirodni flavonoid i antioksidans naringin ...u interakciji s valproatom ublažiti navedene štetne učinke. Mužjaci miševa C57BL/6 bili su svakodnevno tijekom 10 dana izloženi valproatu u dozi od 150 mg/kg i naringinu u dozi od 25 mg/kg te njihovim međusobnim kombinacijama u istim dozama. Nakon pokusnog razdoblja usporedili smo razinu serumskih triglicerida, kolesterola, LDL, HDL i VLDL, jetrene markere PPAR-alfa, PGC-1 alfa, ACOX1 i Nrf2 te antioksidacijske markere SOD, CAT i GSH u jetri. Svaka je jetra analizirana histološki. Valproat je povećao parametre peroksidacije lipida i izazvao izraženu mikrovezikularnu steatozu u cijelom jetrenom lobulu u svim acinarnim zonama, ali je istodobna primjena naringina ograničila steatozu na periferiju lobula. Osim toga, naringin je uspostavio normalnu ravnotežu serumskoga kolesterola, LDL i triglicerida te jetrenih markera PPAR-alfa i PGC-1 alfa, ACOX1 i MDA. Također je povećao aktivnost SOD-a. Svi ovi nalazi upućuju na to da naringin modulira ključne regulatore metabolizma lipida i da ga treba dalje istražiti u ovome modelu, bilo samog ili u kombinaciji s drugim lijekovima ili molekulama za regulaciju lipida.
Alzheimer’s disease (AD) is the most frequent cause of dementia in the elderly, characterized by the presence of cerebral amyloid plaques and neurofibrillary tangles. The causes of the disease are ...not well understood, especially considering that more than 95% of AD patients are non-familial. Due to the similarity of brain regions affected in herpes simplex encephalitis to those mainly affected in AD, and owing to the very high prevalence of latent herpes simplex virus type 1 (HSV1) infection, reactivation of HSV1 was proposed as one of the possible causes of AD. The trigeminal ganglion, located only a few millimeters from the entorhinal cortex, is the primary site of HSV1 latency, although other sites including the sensory neurons, the nodose ganglion of the vagus nerve and other regions of the brain may be involved, possibly in relation to very early neurofibrillary AD changes in the dorsal raphe, locus coeruleus and other brainstem nuclei. Novel data obtained upon infection of cultured neuronal cells and mouse brain with HSV1 further show that HSV1 infection causes intracellular amyloid-beta protein accumulation, as well as abnormal phosphorylation of tau protein, the major component of tangles. Another interesting fact is the existence of a significant degree of homology between HSV1 components and AD susceptibility genes. In this review we summarize findings that reveal connections between the two conditions, as well as different suggestions for the mechanisms of HSV1-induced AD. As most of the available results support a connection of AD and HSV1 infection, antiviral therapy should be taken into consideration for AD treatment following early diagnosis.
Valproat je jedan od najčešće primjenjivanih antiepileptika, a poznato je da prouzročuje poremećenu funkciju proksimalnih bubrežnih tubula. Fiziološki poremećaji i nefrotoksični učinci u nekih ...bolesnika nakon visokih doza ili produljenog uzimanja valproata uključuju disbalans iona u serumu, bubrežnu tubularnu acidozu, proteinuriju, hiperurikozuriju, poliuriju, polidipsiju, dehidraciju i druge poremećaje. U okviru ovog eksperimentalnog rada primijenili smo visoke doze valproata i združeni tretman valproata i naringina u C57Bl/6 miševa. Naringin je poznati antioksidans i protuupalna flavonoidna molekula iz citrusnog voća. Cilj rada bio je utvrditi mogu li biološka svojstva naringina umanjiti štetne učinke na bubrege nakon tretmana valproatom. Valproat je in vivo prouzročio serumsku hiperkalijemiju, izraženiju u mužjaka nego u ženki miševa. Hiperkalijemija prouzročena valproatom bila je ublažena naringinom, a antioksidacijski obrambeni mehanizmi (uglavnom katalaza i smanjena glutationacija) bili su aktivirani, više u ženki. U mužjaka, zajednički tretman valproatom I naringinom nije bio tako učinkovit, a rezultati upućuju na moguće prooksidacijsko djelovanje u bubrežnom tkivu kada se obje tvari primjenjuju zajedno.
Bile is composed of multiple macromolecules, including bile acids, free cholesterol, phospholipids, bilirubin, and inorganic ions that aid in digestion, nutrient absorption, and disposal of the ...insoluble products of heme catabolism. The synthesis and release of bile acids is tightly controlled and dependent on feedback mechanisms that regulate enterohepatic circulation. Alterations in bile composition, impaired gallbladder relaxation, and accelerated nucleation are the principal mechanisms leading to biliary stone formation. Various physiologic conditions and disease states alter bile composition and metabolism, thus increasing the risk of developing gallstones.
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