Local Renin-Angiotensin System at Liver and Crosstalk with Hepatic Diseases

The systemic renin-angiotensin system mainly regulates blood pressure and maintains kidney function. Recent studies have realized that renin-angiotensin system (RAS) has been found in many tissues, such as heart, liver, and kidney. Although RAS in heart and kidney has been well documented, the RAS in the liver has been evaluated in a few studies. Therefore, this chapter will be assessed it. Based on findings, RAS in the liver has presented almost all of its components, such as angiotensin-I (Ang-I), angiotensin-II (Ang-II), angiotensin-converting enzyme (ACE), angiotensin type-1 receptor (AT1), angiotensin type-2 receptor (AT2), named as classical RAS. Expect these components, the local RAS has had alternative pathway components, including angiotensin-converting enzyme 2 (ACE2) and chymase. Classical RAS has an opposite effect of alternative RAS. Although these local RAS might not be such a crucial for the tissue, it could be a more vital function under pathophysiologic conditions. The chapter the local RAS in the liver the under both physiologic and pathophysiologic conditions is highlighted

Pyrethroid Insecticides as the Mitochondrial Dysfunction Inducers

Pyrethroids are used to decrease vector-based health concerns and to increase field yield against agricultural pests. Their metabolism is a concern to disrupt a cell’s homeostatic machinery via reactive oxygen species (ROS) production. They interact with lipid membranes to damage the fine balance between membrane lipids and membrane proteins, especially mitochondrial substrate transporters and electron carriers. Pyrethroids cause a shift in the metabolic energy production strategy, resulting in ROS production and intracellular lipid deposition. The change of open/closed conformation of some mitochondrial membrane proteins increases the vulnerability of mitochondria to Ca2+ ions. Membrane lipid fluidity change is also a concern because of permeability to the substrates and ions to produce energy and other substrates necessary for the cell. Pyrethroids can change the Ca2+ signaling and its interaction with ROS signals via disruption of the fine balance between endoplasmic reticulum and mitochondria. They can disrupt the mitochondrial DNA (mtDNA) via their hydrophobic nature or their ROS production capacity. In conclusion, mitochondria are the center of pyrethroid toxicity, and dysfunction of this organelle via pyrethroid toxicity plays an important role in the fate of cell. Their lipophilic and pro-oxidative nature together with Ca2+ homeostasis plays a synergistic role in this mitochondrial effect

Mitochondrial Dysfunction Associated with Doxorubicin

Cancer prevalence is scaling up each year. Anthracycline groups are still the best chemotherapeutic agent. The most popular anticancer drug in the group is doxorubicin (DOX). Unfortunately, DOX has potent toxicity on noncancerous tissues, e.g., heart, kidneys, etc. However, it is well documented that the severest toxicity of the drug affects heart tissue. Of course, some reasons have been suggested why and/or how the heart is so vulnerable to toxicity. The primary mechanism responsible for DOX’s cardiospecific toxicity remains unidentified so far; however, mitochondrial dysfunction induced by DOX is now considered one of the leading reasons for DOX’s toxicities and undesired side effects. Mitochondrial reactive oxygen production in the heart is a significant contributor to developing mitochondrial dysfunction-exposed DOX based on a variety of evidence. The objective of this review chapter is to critically evaluate and highlight the role of mitochondria in the development of DOX-induced cardiotoxicity

Oksidacijski i apoptotski učinci fluoksetina i njegova metabolita norfluoksetina u vodenbuhe Daphnia magna

The aim of this study was to investigate the oxidative and apoptotic potential of fluoxetine, a widely used antidepressant in Turkey and the world, and of its metabolite norfluoxetine on a model non-target organism, Daphnia magna to see how exposure to this group of antidepressants (specific serotonin reuptake inhibitors) could affect the aquatic environment in which they end up. Juvenile D. magna specimens were chronically exposed to fluoxetine and norfluoxetine alone and in combination at concentrations found in the aquatic environment (0.091 and 0.011 μg/L, respectively) and to their 10-fold environmental concentrations for 21 days. Another group of 17-day-old animals were subacutely exposed to 100-fold environmental concentrations for four days. After exposure, we measured their glutathione peroxidase (GPx) and cholinesterase (ChE) activities, thiobarbituric acid-reactive substances (TBARS), and total protein content spectrophotometrically, while mitochondrial membrane potential (MMP) was analysed by fluorescence staining, and cytochrome c and ERK1/2 protein content by Western blotting. This is the first-time cytochrome c and ERK1/2 were determined at the protein level in D. magna. We also measured their carapace length, width, and caudal spine length microscopically. At environmental concentrations fluoxetine and norfluoxetine caused an increase in ChE activity and brood production. They also caused a decrease in juvenile carapace length, width, and caudal spine length and depolarized the mitochondrial membrane. At 10-fold environmental concentrations, GPx activity, lipid peroxidation levels, cytochrome c, and ERK1/2 protein levels rose. The most pronounced effect was observed in D. magna exposed to norfluoxetine. Norfluoxetine also decreased brood production. Similar effects were observed with subacute exposure to 100-fold environmental concentrations. However, total protein content decreased. All this confirms that fluoxetine and norfluoxetine have oxidative and apoptotic potential in D. magna. Daphnia spp. have a great potential to give us precious insight into the mechanisms of environmental toxicants, but there is still a long way to go before they are clarified in these organisms.Cilj je ovoga istraživanja bio utvrditi oksidacijski i apoptotski potencijal fluoksetina, antidepresiva raširenoga u Turskoj i svijetu, i njegova metabolita norfluoksetina na modelu vodenbuhe Daphnia magna koji nije ciljani organizam djelovanja spojeva. Također smo željeli vidjeti kako izloženost toj skupini antidepresiva (specifičnih inhibitora ponovne pohrane serotonina) može utjecati na vodeni okoliš u kojem oni završe. Mlade jedinke vodenbuhe bile su izložene fluoksetinu (0,091 μg/L) i norfluoksetinu (0,011 μg/L), odvojeno i u kombinaciji, pri koncentracijama zamijećenima u okolišu I deseterostrukim okolišnim koncentracijama u trajanju od 21 dan (kronična izloženost). Jedna je skupina 17 dana starih vodenbuha također bila izložena stostrukoj okolišnoj koncentraciji u trajanju od četiri dana (subakutna izloženost). Potom su u životinja spektrofotometrijom izmjerene aktivnosti enzima glutation peroksidaze (GPx) i kolinesteraza (ChE) te razine reaktivnih tvari tiobarbituratne kiseline (TBARS) i ukupnih proteina. Potencijal mitohondrijske membrane (MMP) utvrđen je fluorescencijom, a proteini citokrom c i ERK1/2 Western blot metodom. Ovo je prvi put da su se u vodenbuhi citokrom c i ERK1/2 utvrđivali na razini proteina. Također je mikroskopski izmjerena dužina i širina oklopa i dužina repne bodlje vodenbuha. Pri okolišnim koncentracijama fluoksetin i norfluoksetin doveli su do povišene aktivnost ChE i većeg razmnožavanja te smanjenja (dužine i širine) karapaksa i repne bodlje u podmlatka i depolarizacije mitohondrijske membrane. Pri deseterostrukim okolišnim koncentracijama porasle su razine aktivnosti GPx, lipidne peroksidacije, citokroma c i ERK1/2 proteina. Norfluoksetin je pritom iskazao najsnažnije djelovanje te doveo do pada razmnožavanja. Slični su učinci primijećeni kod subakutne izloženosti stostrukim okolišnim koncentracijama fluoksetina i norfluoksetina, osim što je ona dovela i do pada ukupnih proteina. Naši rezultati potvrđuju da fluoksetin i norfluoksetin imaju oksidacijski i apoptotski učinak u vodenbuhe. Taj životinjski model može odlično poslužiti za stjecanje uvida u mehanizme toksičnoga djelovanja tvari u okolišu, no potrebna su daljnja istraživanja prije nego što ti mehanizmi postanu potpuno jasni

The Protection of Selenium on Adriamycin-Induced Mitochondrial Damage in Rat

Although adriamycin (ADR) exhibits high anti-tumor efficacy in vitro, its clinical use in cancer chemotherapy is limited due to its high renal toxicity. This study investigated the mechanism of ADR nephropathy and the protective effect of selenium on ADR-induced kidney damage by analyzing of the relationship between selenium and mitochondria. Rats were divided into four groups. The first group was injected with saline i.p. for 21 days, the second group received the 4 mg/kg i.p. ADR every alternate day for 8 days, the third group received the 50 mu g/kg i.p. Se for 21 days, and the fourth group received the Se. ADR co-administration i.p. blood pressures were assessed, the mitochondrial membrane potential (MMP) was assessed, and the adenosine triphosphate (ATP) levels were determined. The total antioxidant (TAS) and oxidant status (TOS) in cytosol, the mitochondria of kidney cells, and plasma were measured. Mitochondrial TAS decreased and TOS increased in the ADR group compared to the Se group. ADR-treated rats showed significantly lower MMP than did the control and Se groups. MMP was significantly restored in the Se + ADR group through selenium treatment compared to the ADR group (p < 0.01). In the ADR group, a reduction in ATP content was seen compared to the control and Se groups (p < 0.01). ATP level was significantly restored through treatment with selenium in the Se + ADR group compared to the ADR group (p < 0.01). We concluded that selenium is effective in vivo against ADR-induced kidney damage via the restoration of TAS and TOS, which prevented mitochondrial damage

Protection Against Adriamycin-Induced Cardiomyopathy by Carnosine in Rats: Role of Endogenous Antioxidants

The aim of this study was to investigate the effects of carnosine, a biological antioxidant, on the acute cardiac damage induced by a single dose of adriamycin in rats. The experimental design consisted of four groups: Control (saline, i.p.); carnosine (CAR; 10 mg/kg/day, i.p.); adriamycin (ADR; 16 mg/kg on the 14th day, i.p.); carnosine with adriamycin. Carnosine was given 2 weeks before and following adriamycin treatment. Blood samples were collected for analysis of plasma creatine kinase (CK) and plasma antioxidant enzymes, glutathione peroxidase (GSH-Px), Cu, Zn-superoxide dismutase (SOD), and catalase (CAT). The rats were then sacrificed, and the hearts were autopsied for hemodynamic study, ECG, and histopathological examination. Results showed that adriamycin produced evident cardiac damage revealed by hemodynamic change, histological alterations, decreased plasma antioxidant enzymes activities, and increased lipid peroxidation to the control value. Carnosine treatment led to significant attenuation of adriamycin-induced cardiomyopathy revealed by normalization of the LVDP, ST interval, CK, SOD, GSH-Px, CAT, and lipid peroxidation. An increase in oxidative stress and inactivation of SOD, GSH-Px, CAT by a single dose of adriamycin were prevented when carnosine was given 2 weeks before and on the same day adriamycin treatment was administered

Effect of salt loading on baroreflex sensitivity in reduced renal mass hypertension

Background: High dietary salt, as well as renal mass reduction, is known to decrease baroreflex sensitivity in rats. However, the effect of high salt intake on baroreflex sensitivity is unknown in reduced renal mass (RRM) hypertension; therefore, the aim of this study was to investigate the effects of salt loading on arterial baroreflex sensitivity and mean arterial pressure (MAP) in RRM hypertension. Methods: Both RRM and sham-operated control (SO) rats were loaded with 0.25 or 0.5% NaCl for five weeks. Plasma Na+, K+, and creatinine levels were measured, and baroreflex sensitivity was evaluated before and after β1 blockade. In addition, cardiac vagal tone and intrinsic heart rate (IHR) were measured. RESULTS: RRM decreased full baroreflex sensitivity of the tachycardic response under 0.5% NaCl loading and the parasympathetic bradycardic response under 0% NaCl loading. The NaCl loading did not affect the severity of RRM hypertension. Cardiac vagal tone and IHR decreased in RRM rats versus SO controls under all NaCl loading conditions. RRM decreased plasma K+ under 0% NaCl loading and increased plasma Na+ under 0.5% NaCl loading. High (0.5%) NaCl loading decreased IHR and increased plasma creatinine and left ventricular weight in RRM rats. CONCLUSIONS: RRM in combination with 0.5% NaCl loading led to a decrease in the sensitivity of full baroreflex and of the parasympathetic component of baroreflex. Changes in plasma Na+ and K+ levels, due to NaCl loading, may have contributed to the decrease in baroreflex sensitivities and IHR but had no effect upon MAP in RRM rats

The relationship between mitogen activated protein kinase and apoptotic proteins in pancreatic beta cell with type-I diabetes

WOS: 000364786400196

The Relationship between Mitogen-Activated Protein Kinase and Apoptotic Proteins in Pancreatic Beta Cell With Type-I Diabetes

WOS: 000360810100139

Mitochondrial Diseases

Mitochondria are crucial organelles for any cell type. Mitochondria take responsibility for not only energy production but also regulation of cell death, also called apoptosis; calcium storage; and heat production. Therefore, mitochondrial disease is implicated in the mode of action of many harmful factors for cells such as drugs and environmental contaminants, dysfunction of the oxygen transport system, malnutrition, intense exercise, and genetic variations. This book presents up-to-date knowledge about mitochondrial disease and its complex relation to some diseases such as cardiac failure, cancer, and Alzheimer's and Parkinson's diseases. This book will, therefore, be essential for readers who are interested in life sciences, especially in medicine