The Possible Role of Nitric Oxide and Oxidative Stress in the Enhanced Apoptosis of Cardiac Cells in Cirrhotic Rats

Abstract- Cirrhosis has been related with hyperdynamic circulation, manifesting as increased cardiac output and decreased systemic vascular resistance. In the present study we examined the cirrhosis outcome on apoptosis of rat hearts. We also tried to explore the role of nitric oxide (NO) and oxidative stress in the probable changed apoptosis of cirrhotic hearts. Twenty eight days after ligation of bile duct, heart tissues were tested for apoptosis. The extent of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been calculated in heart tissues. The cirrhotic hearts exhibited structural defects and greater apoptosis. Chronic treatment of cirrhotic rats with LNAME, a non-selective inhibitor of NO synthase, inhibited heart structural defects and reduced apoptosis of hearts. We also showed that cirrhotic rat hearts had an enhanced level of MDA and reduced activities of CAT, GSHPx and SOD. When the animals were treated by L-NAME chronically, the MDA level reduced and activities of CAT, GSHPx and SOD augmented in cirrhotic heart. In conclusion, increased apoptosis of cirrhotic hearts probably happen due to NO overproduction and increased oxidative stress in hearts of cirrhotic rats

Manganese-Induced Nephrotoxicity Is Mediated through Oxidative Stress and Mitochondrial Impairment

Manganese (Mn) is an essential element that is incorporated in various metabolic pathways and enzyme structures. On the other hand, a range of adverse effects has been described in association with Mn overexposure. Mn is a well-known neurotoxic agent in mammals. Renal injury is another adverse effect associated with Mn intoxication. No precise mechanism for Mn nephrotoxicity has been identified so far. The current study was designed to evaluate the potential mechanisms of Mn-induced renal injury. Rats were treated with Mn (20 and 40 mg/mL, respectively, in drinking water) for 30 consecutive days. Markers of oxidative stress, as well as several mitochondrial indices, were assessed in the kidney tissue. Renal injury was evident in Mn-treated animals, as judged by a significant increase in serum BUN and creatinine. Moreover, urinalysis revealed a significant increase in urine glucose, phosphate, and protein in Mn-treated rats. Kidney histopathological alterations, including tubular atrophy, interstitial inflammation, and necrosis, were also detected in Mn-treated animals. Biomarkers of oxidative stress, including an increment in reactive oxygen species (ROS), lipid peroxidation, and oxidized glutathione (GSSG), were detected in Mn-treated groups. On the other hand, kidney glutathione (GSH) stores and total antioxidant capacity were depleted in Mn groups. Mn exposure was associated with significant mitochondrial depolarization, decreased mitochondrial dehydrogenases activity, mitochondrial permeabilization, and depletion of adenosine triphosphate (ATP) content. These data highlight oxidative stress and mitochondrial impairment as potential mechanisms involved in Mn-induced renal injury

The Possible Role of Nitric Oxide and Oxidative Stress in the Enhanced Apoptosis of Cardiac Cells in Cirrhotic Rats

Abstract- Cirrhosis has been related with hyperdynamic circulation, manifesting as increased cardiac output and decreased systemic vascular resistance. In the present study we examined the cirrhosis outcome on apoptosis of rat hearts. We also tried to explore the role of nitric oxide (NO) and oxidative stress in the probable changed apoptosis of cirrhotic hearts. Twenty eight days after ligation of bile duct, heart tissues were tested for apoptosis. The extent of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been calculated in heart tissues. The cirrhotic hearts exhibited structural defects and greater apoptosis. Chronic treatment of cirrhotic rats with LNAME, a non-selective inhibitor of NO synthase, inhibited heart structural defects and reduced apoptosis of hearts. We also showed that cirrhotic rat hearts had an enhanced level of MDA and reduced activities of CAT, GSHPx and SOD. When the animals were treated by L-NAME chronically, the MDA level reduced and activities of CAT, GSHPx and SOD augmented in cirrhotic heart. In conclusion, increased apoptosis of cirrhotic hearts probably happen due to NO overproduction and increased oxidative stress in hearts of cirrhotic rats

Priprava i ex vivo evaluacija TEC kao promotora apsorpcije tvari u kolonu

In previous studies, it was established that chitosan and its quaternized derivatives are potent enhancers of hydrophilic compounds absorption across intestinal epithelia. The aim of this study was to evaluate the application of a new quaternized chitosan, triethyl chitosan (TEC), in pharmaceutical approaches. TEC was synthesized by a one step process via a 22 factorial design to optimize the preparation conditions. In ex vivo experiments, everted rat colon sac was used to determine the effect of TEC on the penetration of hydrophilic compounds of different molecular masses (e.g., sodium fluorescein and brilliant blue) through colonic epithelia in comparison with chitosan at pH 7.4. These studies indicated a significant increase in absorption of sodium fluorescein and brilliant blue in the presence of TEC compared to chitosan. TEC bearing positive charge is able to interact with the tight junctions of colon epithelia and hence increase the permeation of sodium fluorescein and brilliant blue through the tight junctions. This investigation has shown that triethyl chitosan could be used as a penetration enhancer for poorly absorbable compounds in the colon drug delivery system.U ranijim istraživanjima utrđeno je da su kitozan i njegovi kvartenizirani derivati snažni promotori apsorpcije hidrofilnih spojeva kroz intestinalnu sluznicu. Cilj rada bio je evaluirati novi kvartenizirani kitozan, trietil kitozan (TEC ).TEC je sintetiziran u jednom stupnju. U ex vivo eksperimentima na kolonu štakora praćen je učinak tog polimera na penetraciju hidrofilnih spojeva različitih molekulskih masa (fluorescein natrija i briljant plavila). Rezultati su uspoređivani s učinkom kitozana na pH 7,4. Primjećeno je da TEC značajno povećava apsorpciju ispitivanih tvari u odnosu na nemodificirani kitozan. TEC svojim pozitivnim nabojem dolazi u interakciju s epitelom kolona i tako povećava njegovu permeabilnost. Ispitivanja ukazuju da se trietil kitozan može upotrijebiti kao promotor penetracije za spojeve koji se slabo apsorbiraju u kolonu

Cardiovascular Abnormalities in Cirrhosis: the Possible Mechanisms

Cirrhosis is characterized by marked abnormalities in the cardiovascular system. A hyperdynamic splanchnic and systemic circulation is typical of cirrhotic patients and has been observed in all experimental forms of portal hypertension. The hyperdynamic circulation is most likely initiated by arterial vasodilatation, leading to central hypovolemia, sodium retention, and an increased intravascular volume. Despite the baseline increase in cardiac output, ventricular inotropic and chronotropic responses to stimuli are blunted, a condition known as cirrhotic cardiomyopathy. This review briefly examines the major mechanisms that may underlie these cardiovascular abnormalities, concentrating on nitric oxide, endocannabinoids, prostaglandins, carbon monoxide, endogenou

Protective Effect of Edaravone Against Cyclosporine-Induced Chronic Nephropathy Through Antioxidant and Nitric Oxide Modulating Pathways in Rats

Background: Cyclosporine A (CsA) is an immunosuppressant with therapeutic indications in various immunological diseases; however, its use is associated with chronic nephropathy. Oxidative stress has a crucial role in CsA-induced nephrotoxicity. The present study evaluates the protective effect of edaravone on CsA-induced chronic nephropathy and investigates its antioxidant and nitric oxide modulating property. Methods: Male Sprague-Dawley rats (n=66) were distributed into nine groups, including a control (group 1) (n=7). Eight groups received CsA (15 mg/kg) for 28 days while being treated. The groups were categorized as: • Group 2: Vehicle (n=10) • Groups 3, 4, and 5: Edaravone (1, 5, and 10 mg/kg) (n=7 each) • Group 6: Diphenyliodonium chloride, a specific endothelial nitric oxide synthase (eNOS) inhibitor (n=7) • Group 7: Aminoguanidine, a specific inducible nitric oxide synthase (iNOS) inhibitor (n=7) • Group 8: Edaravone (10 mg/kg) plus diphenyliodonium chloride (n=7) • Group 9: Edaravone (10 mg/kg) plus aminoguanidine (n=7) Blood urea nitrogen and serum creatinine levels, malondialdehyde, superoxide dismutase, and glutathione reductase enzyme activities were measured using standard kits. Renal histopathological evaluations and measurements of eNOS and iNOS gene expressions by RT-PCR were also performed. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey’s test (SPSS software version 18.0). Results: Edaravone (10 mg/kg) significantly attenuated CsA-induced oxidative stress, renal dysfunction, and kidney tissue injury. Aminoguanidine improved the renoprotective effect of edaravone. Edaravone reduced the elevated mRNA level of iNOS, but could not alter the level of eNOS mRNA significantly. Conclusion: Edaravone protects against CsA-induced chronic nephropathy using antioxidant property and probably through inhibiting iNOS gene expression