Evaluating the effects of different fractions obtained from Gundelia tournefortii extract against carbon tetrachloride-induced liver injury in rats

Xenobiotics-induced liver injury is a major challenge for clinicians and pharmaceutical industry. Hence, finding new therapeutic molecules against this complication has clinical value. The current investigation aimed to evaluate the potential protective effects of different fractions obtained from Gundelia tournefortii (GT) hydroalcoholic extract in a rat model of acute hepatic injury. Male Sprague-Dawley rats (200‑250 g) were treated with carbon tetrachloride (CCl4) (1.5 ml/kg, i.p), then ethanol, water, chloroform, ethyl acetate, and n-Butanol fractions of GT extract were administered. Biochemical and histopathological markers of hepatic injury were assessed and glutathione (GSH) and lipid peroxidation were monitored in liver samples. CCl4 administration caused hepatotoxicity as revealed by an increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activity, as well as pathological changes of the liver. Furthermore, a significant reduction in hepatic glutathione content and an elevation in lipid peroxidation were observed in CCl4‑treated rats. It was found that the n‑butanol (200 mg/kg) and the ethyl acetate (300 mg/kg) fractions of GT extract protected liver against CCL4‑induced damage as judged by lower AST, ALT, LDH and lipid peroxidation, prevention of tissue glutathione depletion, and alleviation of histopathological damages of liver in extract‑treated animals. As n‑butanol and the ethyl acetate fractions of GT effectively alleviated the liver injury induced by CCl4 and provide antioxidant properties, we might be able to propose that the hepatoprotective chemicals of Gundelia extract are present in these fractions.</p

Dexamethasone Blunts Lung Inflammation in Cholestatic Mice

Cholestasis/cirrhosis is a multifaceted clinical complication that influences many organs, including the liver, kidney, heart, skeletal muscle, and lung. Cirrhosis-associated lung injury could lead to severe and lethal consequences, including acute respiratory syndrome and patient dearth. Unfortunately, there is no specific pharmacological intervention to manage cholestasis-induced lung injury. It has been revealed that severe inflammation and its associated complications, such as oxidative stress, are involved in the pathogenesis of cholestasis-associated pulmonary damage. The current study was designed to evaluate the role of dexamethasone (DXM) on lung inflammation in cholestatic mice. For this purpose, bile duct ligated (BDL) mice received DXM (1 and 2.5 mg/kg, i.p, 2 times/week) for 14 days. On day 15, the bronchoalveolar lavage fluid (BALF) was prepared. Several markers, including inflammatory cell infiltration, TNF-α, and IgG, were assessed in the BALF of BDL animals. Significant infiltration of inflammatory cells along with increased TNF-α and IgG were detected in the BALF of BDL mice (14 days after surgery). Moreover, significant ROS formation, glutathione depletion, lipid peroxidation, and protein carbonylation were evident in the lung tissue of the BDL group. It was found that DXM (1 and 2.5 mg/kg) significantly blunted inflammation and oxidative stress in the lung of cholestatic mice. Moreover, lung tissue histopathological changes, including inflammatory cell infiltration, were significantly mitigated in DXM-treated mice. These data offer the potential therapeutic effects of DXM against cholestasis-related complications. Therefore, patients with cholestasis-induced lung injury might benefit from repurposing DXM in clinical settings

The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

Taurine (2-aminoethane sulfonic acid) is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid) is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 µM, 100 µM and 1000 µM) of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5‑Fluorouracil, Doxorubicin and Dacarbazine) via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+). Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione) were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug‑treated livers. It was found that taurine (5 and 10 mM) and glycine (5 and 10 mM) administration significantly mitigated the biomarkers of liver injury and attenuated drug‑induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.</p

Thiol-reducing agents abate cholestasis-induced lung inflammation, oxidative stress, and histopathological alterations

Cholestasis is not only influences the hepatic function but also damages many other organs. Lung injury is a critical secondary organ damage associated with cholestasis/cirrhosis. Pulmonary histopathological alterations, respiratory distress, and hypoxia are related to cholestasis/cirrhosis-induced lung injury. It has been found that oxidative stress plays a crucial role in this complication. The current study was designed to investigate the effect of N-acetyl cysteine (NAC) and dithiothreitol (DTT) as thiol-reducing and antioxidant agents against cholestasis-induced lung injury. Bile duct ligated (BDL) rats were monitored for the presence of inflammatory cells, TNF-α, and IgG levels in their broncho-alveolar fluid (BALF) at scheduled time intervals (3, 7, 14, and 28 days post-BDL surgery). These markers reached their highest level in the BALF of BDL rats on day 28 after the surgery. Therefore, in another set of experiments, the BDL animals were treated with NAC (100 and 300 mg/kg/day, i.p, for 28 consecutive days) and DTT (10 and 20 mg/kg/day, i.p, for 28 consecutive days). Meanwhile, a significant increase in the levels of TNF-α and IgG was detected in the BALF of BDL rats. The BALF level of neutrophils, monocytes, and lymphocytes was also significantly increased in cholestatic animals. A significant increase in lung tissue biomarkers of oxidative stress was detected in the BDL rats. It was found that NAC and DTT could significantly blunt pulmonary damage induced by cholestasis. The effects of these agents on oxidative stress biomarkers and inflammatory response seem to play a pivotal role in their mechanisms of protective properties

Equilibrium, Thermodynamic, and Kinetic Studies on Lead (II) Biosorption from Aqueous Solution by Saccharomyces cerevisiae Biomass

This paper presents a biosorption procedure for the preconcentration of Pb(2+) ions using Saccharomyces cerevisiae biomass. The influence of several factors including pH, biomass dosage, contact time, and temperature on biosorption efficiency were optimized. At optimum value of all the equilibrium, thermodynamic, and kinetic parameters of Pb(2+) ion biosorption was investigated by testing the Langmuir and Freundlich models and first and second order kinetic models were applied. The biosorption capacity of S. cerevisiae biomass was determined 89.6 mg/g, while the retained Pb(2+) ions by S. cerevisiae were reversibly eluted using 5 mol/L HNO(3). Due to the high stability of S. cerevisiae the applied biomass can be used successively ten times with a slightly decrease (about 20%) in the recovery of Pb(2+) ions. The calculated thermodynamic parameters, Delta G degrees, Delta H degrees, and Delta S degrees showed that the biosorption of Pb(2+) ion onto S. cerevisiae biomass was feasible, spontaneous, and endothermic under examined conditions. The results of kinetic analysis showed that the biosorption processes of Pb(2+) ions onto S. cerevisiae biomass followed pseudo second order kinetics

Sulfasalazine-induced renal and hepatic injury in rats and the protective role of taurine

Introduction: Sulfasalazine is a drug commonly administrated against inflammatory-based disorders. On the other hand, kidney and liver injury are serious adverse events accompanied by sulfasalazine administration. No specific therapeutic option is available against this complication. The current investigation was designed to evaluate the potential protective effects of taurine against sulfasalazine-induced kidney and liver injury in rats. Methods: Male Sprague-Dawley rats were administered with sulfasalazine (600 mg/kg, oral) for 14 consecutive days. Animals received different doses of taurine (250, 500 and 1000 mg/kg, i.p.) every day. Markers of organ injury were evaluated on day 15th, 24 h after the last dose of sulfasalazine. Results: Sulfasalazine caused renal and hepatic injury as judged by an increase in serum level of creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP). The levels of reactive oxygen species (ROS) and lipid peroxidation were raised in kidney and liver of sulfasalazine-treated animals. Moreover, tissue glutathione reservoirs were depleted after sulfasalazine administration. Histopathological changes of kidney and liver also endorsed organ injury. Taurine administration (250, 500 and 1000 mg/kg/day, i.p) alleviated sulfasalazine-induced renal and hepatic damage. Conclusion: Taurine administration could serve as a potential protective agent with therapeutic capabilities against sulfasalazine adverse effects

Evaluating the effects of different fractions obtained from Gundelia tournefortii extract against carbon tetrachloride-induced liver injury in rats

Xenobiotics-induced liver injury is a major challenge for clinicians and pharmaceutical industry. Hence, finding new therapeutic molecules against this complication has clinical value. The current investigation aimed to evaluate the potential protective effects of different fractions obtained from Gundelia tournefortii (GT) hydroalcoholic extract in a rat model of acute hepatic injury. Male Sprague-Dawley rats (200 250 g) were treated with carbon tetrachloride (CCl4) (1.5 ml/kg, i.p). Then ethanol, water, chloroform, ethyl acetate, and n-Butanol fractions of GT extract were administered. Biochemical and histopathological markers of hepatic injury were assessed, and glutathione (GSH) and lipid peroxidation were monitored in liver samples. CCl4 administration caused hepatotoxicity as revealed by an increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activity, as well as pathological changes of the liver. Furthermore, a significant reduction in hepatic glutathione content and an elevation in lipid peroxidation were observed in CCl4 treated rats. It was found that the n butanol (200 mg/kg) and the ethyl acetate (300 mg/kg) fractions of GT extract protected liver against CCL4 induced damage as judged by lower AST, ALT, LDH and lipid peroxidation, prevention of tissue glutathione depletion, and alleviation of histopathological damages of liver in the extract treated animals. As n butanol and the ethyl acetate fractions of GT effectively alleviated the liver injury induced by CCl4 and provided antioxidant properties, we might be able to propose that the hepatoprotective chemicals of GT extract are present in these fractions

Concurrent Inflammation Augments Antimalarial Drugs-Induced Liver Injury in Rats

Purpose: Accumulating evidence suggests that drug exposure during a modest inflammation induced by bacterial lipopolysaccharide (LPS) might increase the risk of drug-induced liver injury. The current investigation was designed to test if antimalarial drugs hepatotoxicity is augmented in LPS‑treated animals. Methods: Rats were pre-treated with LPS (100 µg/kg, i.p). Afterward, non-hepatotoxic doses of amodiaquine (25, 50 and 100 mg/kg, oral) and chloroquine (25, 50 and 100 mg/kg, oral) were administered. Results: Interestingly, liver injury was evident only in animals treated with both drug and LPS as estimated by pathological changes in serum biochemistry (ALT, AST, LDH, and TNF-α), and liver tissue (severe hepatitis, endotheliitis, and sinusoidal congestion). An increase in liver myeloperoxidase enzyme activity, lipid peroxidation, and protein carbonylation, along with tissue glutathione depletion were also detected in LPS and drug co-treated animals. Conclusion: Antimalarial drugs rendered hepatotoxic in animals undergoing a modest inflammation. These results indicate a synergistic liver injury from co-exposure to antimalarial drugs and inflammation

Effects of hydroalcoholic extract of Ziziphus jujuba on acetic acid induced ulcerative colitis in male rat (Rattus norvegicus)

ABSTRACT Objective: To investigate the effects of hydroalcoholic extract of Ziziphus jujuba on the histopathological, tissue oxidative stress and inflammation plus to antioxidant pathways of colon tissue in rat with induced Ulcerative colitis. Materials and methods: Ulcerative colitis was induced in 80 rats those divided into 8 equal groups. Group 1 and 2 were negative controls receiving 1 mL/day of normal saline in enema and oral; group 3 and 4 as positive control 1 and 2 received 10 mg/kg of intra-colonic asacol and oral mesalazine; groups 5 and 6 received 20% and 40% of hydroalcoholic extract of Z. jujuba trans-rectally; group 7 and 8 received 1500 and 3000 mg/kg of hydroalcoholic extract of Z. jujuba orally, respectively. After 7 days, animals were evaluated for colon tissue histopathology, levels of malondialdehyde and IL-1&#946;, and activities of superoxide dismutase, glutathione peroxidase and myeloperoxidase in colon tissue. Results: Hydroalcoholic extract of Z. jujuba in both forms of trans-rectal and oral administration especially in the higher doses could result into a more healing effect in damaged colonic tissue, more reduce glutathione peroxidase and IL-1&#946; level. Also, these two doses (gel 40% and oral 3000 mg/kg) could more decrease the myeloperoxidase activity and stimulate superoxide dismutase and glutathione peroxidase activities. Also, gel 40% in transrectal administration was more potent than administration 3000 mg/kg in oral. Conclusion: The results of the present study indicated that Z. jujube may be considered as a treatment of choice for Ulcerative colitis especially in gel form and also in dose-dependent pattern